Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

This article reports a case of an elderly male patient presenting with nephrotic syndrome. Renal biopsy pathology indicated membranous nephropathy, with both renal tissue staining for M-type phospholipase A2 receptor (PLA2R) and serum anti-PLA2R antibodies being negative. Nephrotic syndrome achieved remission following treatment with prednisone combined with tacrolimus; however, the patient relapsed during tacrolimus maintenance therapy. Subsequent laboratory evaluation revealed positive anti-nuclear antibodies and anti-double-stranded DNA antibodies, accompanied by decreased complement levels. Exostosin 1 and Exostosin 2 staining performed on the initial renal biopsy specimen yielded positive results, leading to a diagnosis of lupus nephritis. Due to the patient's history of rituximab-related allergic reactions, pulmonary infection, and acute kidney injury, the subsequent treatment regimen consisted of obinutuzumab sequentially combined with belimumab, in addition to prednisone 10 mg/d. During the two-year follow-up period, the patient's anti-double-stranded DNA antibodies converted to negative, complement levels normalized, proteinuria achieved complete remission, and no adverse events such as severe infection occurred. This article reviews the diagnosis, treatment, and relevant literature for this case, aiming to provide clinical insights for the early diagnosis and selection of therapeutic strategies for similar patients.

In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.

A 32-year-old female patient experienced a foreign body sensation in her esophagus on the evening of September 22, 2024, after consuming undercooked grass carp at a restaurant in Wuhan. Esophagoscopy conducted at the hospital revealed no abnormalities. Three days later, she had a stabbing pain in the pharynx. On October 8, upon self-examination, she noticed a red brown worm exhibiting stretching and contracting movements attached near the uvula in her pharynx and then went to the hospital. During the removal of the worm, the doctor observed the ulcers on the mucous membrane. Serological antibody tests for seven common human parasitic worms, including Schistosoma japonicum, Paragonimus westermani, Clonorchis sinensis, cysticercus of Taenia solium, sparganum, hydatid cyst, and Trichinella spiralis, were all negative. The isolated worm was reddish brown, measuring 4 mm in length and 2 mm in width. Staining with hydrochloric carmine dye revealed a morphology consistent with Clinostomum complanatum (Rud., 1819), characterized by an oral sucker at the anterior end, a pharynx connecting to intestinal branches, and two intestinal branches extending to the posterior end of the body with small sub-branches. The ventral sucker, larger than the oral sucker, was located at the front 1/4 of the body. A pair of testes were arranged longitudinally in the mid-posterior part, with an ovary located between the two testes and a uterus located above the upper testis. A comprehensive search of 188 databases comprising more than 460 million full-text articles through the library of Huazhong University of Science and Technology confirmed the first reported case of Clinostomum complanatum infection in humans in China.

Objective To explore the relationship between osteoporosis and carotid atherosclerosis in patients with coronary heart disease aged≥60 years and analyze prevention suggestions. Methods The clinical data of 380 patients with coronary heart disease aged≥60 years who underwent various examinations in the hospital between April 2024 and April 2025 were retrospectively analyzed. According to the bone mineral density (BMD) classification criteria, the patients were divided into osteoporosis group and non-osteoporosis group. The differences in general data and carotid atherosclerosis-related indicators were compared between osteoporosis group and non-osteoporosis group. Pearson method was used to analyze the correlation between carotid atherosclerosis indicators and clinical indicators in patients with coronary heart disease aged≥60 years. According to the IMT detection thickness in patients with coronary heart disease and osteoporosis aged≥60 years were divided into IMT thickening group and IMT non-thickening group and between plaque group and non-plaque group, and the differences in BMD and bone metabolism indicators were compared. Binary logistics analysis was adopted to analyze the risk factors of IMT thickening and carotid plaque formation in patients with coronary heart disease≥60 years old. Results Age and duration of osteoporosis group TC、LDL-C、CTX、 Carotid artery IMT and carotid atherosclerosis degree were higher than those in the non osteoporosis group, the difference was statistically significant (P<0.05). BMI, OPG, OCN, 25 (OH) D, BMD, carotid artery elasticity coefficient were lower than those in the non osteoporosis group, the difference was statistically significant (P<0.05). Carotid IMT, carotid atherosclerosis degree, and carotid elasticity coefficient were significantly correlated with age, course of disease, TC, LDL-C, CTX, BMI, OPG, OCN, BMD, and 25 (OH) D of coronary heart disease patients ≥60 years old (P<0.05). OPG, OCN, BMD and 25(OH)D in IMT thickening group and plaque group were lower compared to IMT non-thickening group and non-plaque group (P<0.05) while CTX was significantly higher than that in IMT non-thickening group and non-plaque group (P<0.05). Binary logistics regression analysis showed that OPG, OCN, BMD, 25(OH)D and CTX were associated with IMT thickening in patients with coronary heart disease and osteoporosis aged≥60 years (P<0.05). OPG, OCN and BMD were associated with carotid plaque formation in patients with coronary heart disease complicated with osteoporosis aged≥60 years (P<0.05). Conclusion There is a significant correlation between osteoporosis and arteriosclerosis in patients with coronary heart disease aged≥60 years. As the bone mass decreases, the manifestations of arteriosclerosis become become more and more obvious, which needs attention and prevention.

Intervertebral disc degeneration (IDD) is the main cause of low back pain. Immune cells play an extremely important role in regulating the progression of IDD by interacting with nucleus pulposus (NP) cells and the extracellular matrix (ECM). Healthy NP tissue is a vascular-free and immune-privileged tissue that does not normally interact with macrophages. However, the establishment of neovascularization channels in damaged intervertebral discs has led to extensive cross-talk between NP and macrophages, with different results depending on microenvironmental stimuli. Based on this, this review reviewed the correlation between IDD and low back pain, summarized the source and function of macrophages, and discussed the possible regulatory mechanism between macrophages and discogenic pain. Finally, potential therapies targeting macrophages to delay IDD in recent years were also discussed, aiming to emphasize the important role of immunology in IDD and provide a new direction for the prevention and treatment of IDD.
Humans ; Intervertebral Disc Degeneration/complications* ; Macrophages/immunology* ; Low Back Pain/immunology* ; Nucleus Pulposus ; Animals ; Extracellular Matrix

Based on whole-genome identification of the TPS gene family in Perilla frutescens and screening, cloning, bioinformatics, and expression analysis of the synthetic enzyme for the insect-resistant component germacrene D, this study lays the foundation for understanding the biological function of the TPS gene family and the insect resistance mechanism in P. frutescens. This study used bioinformatics tools to identify the TPS gene family of P. frutescens based on its whole genome and predicted the physicochemical properties, systematic classification, and promoter cis-elements of the proteins. The relative content of germacrene D was detected in both normal and insect-infested leaves of P. frutescens, and the germacrene D synthase was screened and isolated. Gene cloning, bioinformatics analysis, and expression profiling were then performed. The results showed that a total of 99 TPS genes were identified in the genome, which were classified into the TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g subfamilies. Conserved motif analysis showed that the TPS in P. frutescens has conserved structural characteristics within the same subfamily. Promoter cis-element analysis predicted the presence of light-responsive elements, multiple hormone-responsive elements, and stress-responsive elements in the TPS family of P. frutescens. Transcriptome data revealed that most of the TPS genes in P. frutescens were highly expressed in the leaves. GC-MS analysis showed that the relative content of germacrene D significantly increased in insect-damaged leaves, suggesting that it may act as an insect-resistant component. The germacrene D synthase gene was screened through homologous protein binding gene expression and was found to belong to the TPS-a subfamily, encoding a 64.89 kDa protein. This protein was hydrophilic, lacked a transmembrane structure and signal peptide, and was predominantly expressed in leaves, with significantly higher expression in insect-damaged leaves compared to normal leaves. In vitro expression results showed that germacrene D synthase tended to form inclusion bodies. Molecular docking showed that farnesyl pyrophosphate(FPP) fell into the active pocket of the protein and interacted strongly with six active sites. This study provides a foundation for further research on the biological functions of the TPS gene family in P. frutescens and the molecular mechanisms underlying its insect resistance.
Perilla frutescens/chemistry* ; Plant Proteins/chemistry* ; Multigene Family ; Sesquiterpenes, Germacrane/metabolism* ; Alkyl and Aryl Transferases/chemistry* ; Phylogeny ; Gene Expression Regulation, Plant

Cistanches Herba(CH) is a famous tonic traditional Chinese medicine, with the effects of tonifying kidney Yang, nourishing kidney Yin, replenishing essence and blood, and moistening the intestines to relieve constipation. Modern pharmacological studies have shown that CH has anti-aging, anti-fatigue, immunomodulatory, neuroprotective, and anti-aging activities, serving as an ideal raw material for the development of pharmaceuticals and health products. In 2023, CH was added in the catalog of medicinal and food substances, which provided policy support for its application in conventional food products and expanding pathways for industrial diversification. To comprehensively understand current development status of CH products, this review systematically investigated professional databases including Yaozhi(https://db.yaozh.com), Chinese Pharmacopoeia, Compendium of National Standards for Chinese Patent Medicines, and Kezhuang and collected market survey data to thoroughly review the applications of CH as a primary ingredient in domestic and international Chinese patent medicines, health foods, cosmetics, and common food products. Furthermore, this review points out challenges in the current industrial development and future potential market prospects, aiming to provide guidance for the development and industrialization of CH-based pharmaceuticals and health products, thereby promoting the vigorous growth of the CH industry.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Cistanche/chemistry* ; Animals ; Medicine, Chinese Traditional