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.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

This paper has summarized current studies on retinitis pigmentosa （RP） from two perspectives， which were disease mechanism insights from western medicine， and etiology， pathogenesis and therapeutic principles in traditional Chinese medicine （TCM）. From the perspective of western medicine， the understanding of RP has evolved from an early single-factor explanation focusing on pathogenic gene mutations to a more comprehensive， multifactorial model involving genetic abnormalities， photoreceptor cell degeneration， retinal pigment epithelium dysfunction， oxidative stress， inflammatory responses， microenvironmental imbalance， and vascular insufficiency. In TCM， RP is considered to be a disorder manifested in the eyes but rooted in dysfunction of the zang-fu （脏腑） organs. Its pathogenesis is primarily associated with congenital insufficiency， liver-kidney depletion， impaired spleen function of transportation and transformation， and stasis obstructing the meridians. The core pathological mechanism can be summarized as "deficiency complicated by stasis"， emphasizing holistic imbalance， dynamic disease progression， and syndrome differentiation and treatment. The differences and complementarities between the two medical systems in understanding disease progression are further discussed. RP is proposed to be more appropriately regarded as a complex disease characterized by long-term progression， stage-dependent evolution， and persistent decompensation. Western medicine contributes to elucidating the molecular mechanisms underlying RP and provides the foundation for targeted therapeutic interventions， whereas TCM offers a holistic perspective for understanding disease evolution through the assessment of overall functional status， disease-stage stratification， and long-term syndrome-based regulation.

Based on the epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase(MAPK) signaling pathway-mediated cell proliferation, this study explores the effect of cisplatin combined with Guiqi Yiyuan Ointment on Lewis lung cancer-bearing mice. A total of 60 male C57BL/6 mice were randomly divided into a blank group with 10 mice and a modeling group with 50 mice. After modeling, they were randomly divided into the model group, cisplatin group, and low-, medium-, and high-dose groups of cisplatin combined with Guiqi Yiyuan Ointment, with 10 mice in each group. After 14 days of medication, the general condition of the mice was observed; body weight was measured, and organ index and tumor inhibition rate were calculated. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology changes in tumor tissue. Immunohistochemistry was used to detect the positive rate of Ki-67 antigen(Ki-67) and proliferating cell nuclear antigen(PCNA) in tumor tissue. Western blot and real time-quantitative polymerase chain reaction(qPCR) were used to detect the expression of related proteins and mRNA in tumor tissue. Flow cytometry was used to detect the cell cycle of tumor cells in tumor tissue. The results showed that compared with that in the blank group, the general condition of mice in the model group deteriorated; the body weight, as well as thymus and spleen index of mice in the model group decreased after 14 days of medication. Compared with that in the model group, the general condition of mice in the cisplatin group deteriorated, while the condition of mice in the combined groups improved; the body weight, as well as thymus and spleen index of mice in the cisplatin group decreased, while the three indicators in the combined groups increased; the tumor weight of each medication group decreased, and the tumor inhibition rate increased; there were varying degrees of necrosis in tumor cells of each medication group, and the tightness of tumor cells, the increase in the number of cell nuclei and chromatin, and mitosis all decreased. The positive rate of Ki-67 and PCNA, as well as the protein expression and ratio of p-EGFR/EGFR, rat sarcoma viral oncogene homolog(Ras), phosphorylated Raf-1 protein kinase(p-Raf-1)/Raf-1, phosphorylated mitogen-activated protein kinase kinase(p-MEK)/MEK, phosphorylated extracellular signal-regulated kinase(p-ERK)/ERK and the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK all decreased. The proportion of tumor cells in the G_0/G_1 phase of each medication group increased, and that in the S phase decreased. In addition, there was no significant difference in the G_2/M phase. Compared with that of the cisplatin group, the tumor weight of the combined groups decreased, and the tumor inhibition rate increased. The necrosis and mitosis of tumor cells in the combined groups were more pronounced; the positive rate of Ki-67 and PCNA, the protein expression and ratio of p-EGFR/EGFR, Ras, p-Raf-1/Raf-1, p-MEK/MEK, and p-ERK/ERK, as well as the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK in the combined groups all decreased. The proportion of tumor cells in the G_0/G_1 phase of the combined medium-and high-dose groups increased, and that in the S phase decreased. There was no significant difference in the proportion of tumor cells of the combined groups in the G_2/M phase. This indicates that the combination of cisplatin and Guiqi Yiyuan Ointment can enhance the anti-tumor effect of cisplatin on tumor-bearing mice, and the mechanism may be associated with the inhibition of the EGFR/MAPK pathway, which accelerates the arrest of tumor cells in the G_0/G_1 phase, thereby inhibiting the proliferation of tumor cells. At the same time, the study also indicates that Guiqi Yiyuan Ointment may reduce the damage of tumors to mice and the toxic side effects brought by cisplatin chemotherapy.
Animals ; Male ; Carcinoma, Lewis Lung/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; ErbB Receptors/genetics* ; Mice ; Cisplatin/administration & dosage* ; Mice, Inbred C57BL ; Cell Proliferation/drug effects* ; Ointments/administration & dosage* ; MAP Kinase Signaling System/drug effects* ; Humans ; Antineoplastic Agents/administration & dosage* ; Lung Neoplasms/metabolism*

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans ; MicroRNAs/metabolism* ; Berberine/pharmacology* ; Hep G2 Cells ; Exosomes/genetics* ; Aquaporin 4/metabolism* ; Insulin Resistance ; Astrocytes/drug effects*

Amber and subfossil resins are subjects of interdisciplinary research across multiple fields. However, due to their diverse origins and complex compositions, different disciplines vary in their definitions and functional interpretations. In traditional Chinese medicine(TCM), amber has been utilized as a medicinal material since ancient time, with extensive historical documentation. However, its classification, provenance, and nomenclature remain ambiguous, and authentic medicinal amber artifacts are exceedingly rare. This study employed Fourier-transform infrared spectroscopy(FTIR) to characterize amber and subfossil resins from various geological sources and commercially "medicinal amber". Additionally, historical literature and market surveys were analyzed to explore their provenance, composition, and functional attributes. The results indicate that amber and subfossil resins from different sources and with different compositions exhibit distinct fingerprint characteristics in the FTIR spectral range of 1 800-700 cm~(-1). "Medicinal amber" available in the market primarily consists of subfossil or modern resins, significantly differing in composition and structure from geological amber. This study highlights the importance of interdisciplinary research on amber identification and resource management. It is essential to establish a systematic database of amber and subfossil resin characteristics and integrate modern analytical techniques to enhance research on their composition, pharmacological mechanisms, and potential therapeutic effects, thereby promoting the standardized utilization of amber resources and advancing the modernization of TCM.
Amber/history* ; Archaeology ; Spectroscopy, Fourier Transform Infrared ; Medicine, Chinese Traditional

This study compared the differences in intestinal absorption characteristics of eleven active components in Rubus multibracteatus(RM) extract(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, epicatechin, catechin, xanthotoxin, p-coumaric acid, caffeic acid, and apigenin-7-O-glucuronide) between normal rats and inflammatory pain model rats using the in-vitro everted intestinal sac model. The RM extract was administered at absorption concentrations of 25.0, 50.0, and 100.0 mg·mL~(-1). The contents of the eleven components in intestinal absorption solution samples were quantified by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), and their cumulative absorption(Q) and absorption rate constant(K_a) were calculated to evaluate the absorption characteristics of these components in normal rats and inflammatory pain model rats. The results show that except for catechin, epicatechin, and caffeic acid, the cumulative absorption-time curves of the other eight components(protocatechuic acid, tiliroside, scutellarin, luteoloside, astragalin, xanthotoxin, p-coumaric acid, and apigenin-7-O-glucuronide) exhibit an upward trend without saturation, with correlation coefficients(R~2) all > 0.9, indicating linear absorption. However, the overall absorption of all components is not dose-dependent with increasing concentration, suggesting that their absorption mechanisms are not solely passive diffusion. In both normal and model rats, the jejunum shows the highest absorption for all components except xanthotoxin. The overall absorption of seven components(excluding protocatechuic acid, caffeic acid, apigenin-7-O-glucuronide, and luteoloside) in normal rats is better than that in model rats across all intestinal segments. These findings indicate that the pathological state of inflammatory pain alters the intestinal absorption of RM extract, and its mechanism needs further investigation.
Animals ; Rats ; Intestinal Absorption/drug effects* ; Male ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/metabolism* ; Disease Models, Animal ; Pain/metabolism* ; Intestines/drug effects* ; Intestinal Mucosa/metabolism*

Amid the global wave of digital economy, China's medical artificial intelligence applications are rapidly advancing through technological innovation and policy support, while facing multifaceted evaluation and regulatory challenges. The dynamic algorithm evolution undermines the consistency of assessment criteria, multimodal systems lack unified evaluation metrics, and conflicts persist between data sharing and privacy protection. To address these issues, the China National Health Development Research Center has established a value assessment framework for artificial intelligence medical technologies, formulated the country's first technical guideline for clinical evaluation, and validated their practicality through scenario-based pilot studies. Furthermore, this paper proposes introducing a "regulatory sandbox" model to test technical compliance in controlled environments, thereby balancing innovation incentives with risk governance.
Artificial Intelligence/legislation & jurisprudence* ; China ; Humans ; Algorithms