Osteoporosis （OP） is a metabolic disorder characterized by microstructural deterioration of bone and increased bone fragility due to reduced bone mass， which can cause the development of bone-related diseases. This condition imposes significant economic and psychological burdens on patients. While modern medicine has extensively researched the pathogenesis of OP， it remains incompletely understood. Current clinical management primarily relies on anti-resorptive drugs and synthetic metabolic agents. However， long-term use of some medications may yield suboptimal therapeutic outcomes and lead to severe adverse reactions. Given the necessity for prolonged or lifelong treatment for OP， there is a critical need to identify highly effective， safe， and cost-effective pharmaceutical interventions. In light of evolving disease management paradigms and recent advancements in OP research， traditional Chinese medicine has demonstrated emerging advantages in addressing this condition. Through literature review， this study delves into the pathogenesis of OP from five perspectives： hormonal dysregulation， autophagy， ferroptosis， oxidative stress， and intestinal flora alteration. Furthermore， it summarizes the therapeutic efficacy and specific mechanisms of traditional Chinese medicine monomers and compound formulas against OP through regulating hormone levels， interfering with autophagy， inhibiting ferroptosis， counteract oxidative stress，and maintain intestinal flora balance. These multifaceted insights are expected to provide theoretical reference and guide future clinical traditional Chinese medicine approaches for preventing and managing OP.

BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Tooth loss is a common oral problem, and cognitive decline is a primary manifestation of neurodegenerative diseases in the elderly. Both conditions affect their daily living abilities and quality of life. Studies have shown that tooth loss may negatively impact cognitive function through physiological mechanisms such as neural pathways and inflammatory factors, and social, psychological and behavioral factors are identified as important modifiable elements for preventing cognitive decline. This review examined literature about tooth loss and cognitive decline in the elderly, and explored the potential pathways of social, psychological and behavioral factors between these two conditions. The findings indicated that tooth loss may increase the risk of cognitive decline through reduced social participation, social isolation and limited social capital, increased chronic stress, depression and negative aging attitudes, as well as altered physical activity patterns, sleep duration and diets. For the elderly with tooth loss, targeted preventive and intervention measures addressing social, psychological and behavioral aspects can be implemented to prevent and delay cognitive decline, thereby improving their quality of life.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. The advancement of its precise diagnosis and therapeutic development urgently requires in vitro models that can highly recapitulate the pathophysiological characteristics of human tissues. Organ-on-a-chip has emerged as a novel technological platform that integrates microfluidic engineering, biomaterials, and other engineering strategies with organoid culture. This platform enables precise control over the cellular microenvironment, thereby closely mimicking the three-dimensional structure and physiological functions of human organs in vitro. Organ-on-a-chip systems demonstrate significant advantages in cancer research, developmental biology, and disease modeling, as they not only preserve the heterogeneity and pathological features of patient samples but also support co-culture of various cell types to reconstruct the tumor microenvironment (TME). However, standardized construction methods and integrated analytical strategies for this technology in lung cancer research remain to be further refined. This review systematically elaborates on the key technical principles of organ-on-a-chip and its recent advances in lung cancer modeling, drug screening, and immunotherapy research. It aims to provide a theoretical foundation and technical perspective for promoting the deeper application of organ-on-a-chip in precision medicine and translational research for lung cancer.
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Humans ; Lung Neoplasms/drug therapy* ; Organoids/drug effects* ; Lab-On-A-Chip Devices ; Animals ; Tumor Microenvironment

Bone repair remains an important target in tissue engineering, making the development of bioactive scaffolds for effective bone defect repair a critical objective. In this study, β-tricalcium phosphate (β-TCP) scaffolds incorporated with processed pyritum decoction (PPD) were fabricated using three-dimensional (3D) printing-assisted freeze-casting. The produced composite scaffolds were evaluated for their mechanical strength, physicochemical properties, biocompatibility, in vitro pro-angiogenic activity, and in vivo efficacy in repairing rabbit femoral defects. They not only demonstrated excellent physicochemical properties, enhanced mechanical strength, and good biosafety but also significantly promoted the proliferation, migration, and aggregation of pro-angiogenic human umbilical vein endothelial cells (HUVECs). In vivo studies revealed that all scaffold groups facilitated osteogenesis at the bone defect site, with the β-TCP scaffolds loaded with PPD markedly enhancing the expression of neurogenic locus Notch homolog protein 1 (Notch1), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and osteopontin (OPN). Overall, the scaffolds developed in this study exhibited strong angiogenic and osteogenic capabilities both in vitro and in vivo. The incorporation of PPD notably promoted the angiogenic-osteogenic coupling, thereby accelerating bone repair, which suggests that PPD is a promising material for bone repair and that the PPD/β-TCP scaffolds hold great potential as a bone graft alternative.
Calcium Phosphates/chemistry* ; Animals ; Bone Regeneration ; Rabbits ; Tissue Scaffolds ; Printing, Three-Dimensional ; Humans ; Human Umbilical Vein Endothelial Cells ; Neovascularization, Physiologic ; Osteogenesis ; Tissue Engineering/methods* ; Biomimetic Materials ; Cell Proliferation ; Angiogenesis

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Patients with severe pneumonia caused by novel coronavirus infection are often complicated with acute respiratory distress syndrome (ARDS), which has a high mortality. ARDS is characterized by diffuse alveolar damage, pulmonary edema, and hypoxemia. Mitochondria are prone to morphological and functional abnormalities under hypoxia and viral infection, which can lead to cell apoptosis and damage, severely impacting the disease progression. Mitochondria maintain homeostasis through fission and fusion. In ARDS, hypoxia leads to the phosphorylation of dynamin-related protein 1 (Drp1), triggering excessive mitochondrial fission and damaging the alveolar epithelial barrier. Animal experiments have shown that inhibiting this process can alleviate lung injury, providing a potential direction for treatment. The pathology of novel coronavirus infection-related ARDS is similar to that of typical ARDS but more severe. Viral infection and hypoxia disrupt the mitochondrial balance, causing fission and autophagy abnormalities, promoting oxidative stress and mitochondrial DNA (mtDNA) release, activating inflammasomes, inducing the expression of hypoxia-inducible factor-1α (HIF-1α), exacerbating viral infection, inflammation, and coagulation reactions, and resulting in multiple organ damage. Mechanical ventilation and glucocorticoids are commonly used in the treatment of novel coronavirus infection-related ARDS. Mechanical ventilation is likely to cause lung and diaphragm injuries and changes in mitochondrial dynamics, while the lung protective ventilation strategy can reduce the adverse effects. Glucocorticoids can regulate mitochondrial function and immune response and improve the patient's condition through multiple pathways. The mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS is caused by hypoxia and viral proteins, leading to lung and multiple organ injuries. To clarify the pathophysiological mechanism of mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS and explore effective strategies for regulating mitochondrial dynamics balance to treat this disease, so as to provide new treatment targets and methods for patients with novel coronavirus infection-related ARDS. The existing treatments have limitations. Future research needs to deeply study the mechanism of mitochondrial dysfunction, develop new therapies and regulatory strategies, and improve the treatment effect.
Humans ; Respiratory Distress Syndrome/etiology* ; COVID-19 ; Mitochondrial Dynamics ; Mitochondria/metabolism* ; DNA, Mitochondrial ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Dynamins ; SARS-CoV-2