Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

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:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

OBJECTIVE: To review clinical application and research progress of different types of intelligent responsive hydrogels in repairing articular cartilage injury. METHODS: The animal experiments and clinical studies of different types of intelligent responsive hydrogels for repairing articular cartilage injury were summarized by reviewing relevant literature at home and abroad. RESULTS: The intrinsic regenerative capacity of articular cartilage following injury is limited. Intelligent responsive hydrogels, including those that are temperature-sensitive, light-sensitive, enzyme-responsive, pH-sensitive, and other stimuli-responsive hydrogels, can undergo phase transitions in response to specific stimuli, thereby achieving optimal functionality. These hydrogels can fill the injured cartilage area, promote the proliferation and differentiation of chondrocytes, and expedite the repair of the damaged site. With advancements in cartilage tissue engineering materials research, intelligent responsive hydrogels offer a novel approach and promising potential for the treatment of cartilage injuries. CONCLUSION Intelligent responsive hydrogel is a kind of flexible, controllable, efficient, and stable polymer, which has similar structure and functional properties to articular cartilage, and has become one of the important biomaterials for cartilage repair. However, there is still a lack of unified treatment standards and simple and efficient preparation technology.
Hydrogels/therapeutic use* ; Cartilage, Articular/injuries* ; Tissue Engineering/methods* ; Humans ; Animals ; Chondrocytes/cytology* ; Biocompatible Materials/chemistry* ; Tissue Scaffolds/chemistry*

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity