Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

Objective: To evaluate the effect of community comprehensive management model intervention among patients with dyslipidemia, so as to provide the reference for optimizing community management strategies and improving the target achievement rate for blood lipids among this population. Methods: From May to June 2023, a multi-stage stratified random sampling method was employed to select patients with dyslipidemia from primary healthcare institutions in Jiaxing City, Zhejiang Province. Eligible participants were randomly assigned to either a control group or an intervention group. The control group received routine management, while the intervention group was subjected to a community comprehensive management model in addition to the routine care. Both groups were followed up for 24 months. Data on demographic characteristics, lifestyle behaviors, physical examination indices, and blood biochemical indicators were collected at baseline and after the intervention through questionnaires, physical examinations, and laboratory tests. Changes in obesity rate, central obesity rate, target achievement rates for blood lipids, blood pressure, and blood glucose, as well as lifestyle modifications, were analyzed. Differences between the two groups before and after the intervention were assessed using generalized estimating equations (GEE). Results: The control group consisted of 560 patients, including 303 females (54.11%) and 430 individuals aged ≥65 years (76.79%). The intervention group also included 560 patients, with 300 females (53.57%) and 431 individuals aged ≥65 years (76.96%). Before the intervention, no statistically significant differences were observed between the two groups in terms of gender, age, educational level, history of chronic diseases, and atherosclerotic cardiovascular disease risk stratification (all P>0.05). After 24 months of intervention, interaction effects between group and time were observed for obesity rate, central obesity rate, target achievement rate for blood lipids, target achievement rate for blood glucose, composite target achievement rate, physical activity rate, and medication adherence (all P<0.05). Specifically, the intervention group demonstrated lower rates of obesity and central obesity, and higher target achievement rate of blood lipids, target achievement rate of blood glucose, composite target achievement rate, physical activity rate, and medication adherence compared to the control group. Conclusion The community comprehensive management model contributed to improvements in multiple metabolic parameters (including body weight, waist circumference, blood lipids, and blood glucose) among patients with dyslipidemia, and was associated with increased physical activity rate and medication adherence.

National biological standards for antibiotics are critical components of the antibiotic quality control system and serve as reference materials for measuring and calibrating the biological activity of antibiotics. This article systematically reviews the classification, definition of potency units, and current research status of commercially available national antibiotic biological standards in China. At present, these standards can be categorized based on chemical structure, number of components, and development methods. The definition of potency units has evolved from an early “arbitrarily assigned unit” to “being represented by the mass of the antibiotic salt” and, more recently, to the current mainstream approach of “being represented by the mass of the active ingredient”. This evolution reflects a shift in quality control philosophy from primarily biological analysis to a system dominated by chemical analysis supplemented by biological methods. Current research focuses on optimizing potency determination methods, studying the unification of content and potency, and implementing dual quality control of both the potency and the ratio/content of active components in multi-component antibiotics. For complex multi-component antibiotics, the microbiological assay based on biological activity remains irreplaceable in quality control. Future efforts should emphasize further method optimization, ensuring batch-to-batch consistency of standards, and advancing precision quality control as key research priorities for antibiotic biological standards.

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.

Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

OBJECTIVE To investigate the regulatory effect of vitamin D3(VD3)-mediated TIPE2 on macrophage function and phenotype in chronic rhinosinusitis with nasal polyps(CRSwNP).METHODS Peripheral blood samples were collected from 100 CRSwNP patients and 100 patients with simple nasal septum deviation.RT-qPCR and Western blot were used to measure the expression of TIPE2 and Arg-1,and chemiluminescence was used to measure VD3 concentration.In the J774A.1 macrophage cell line,TIPE2 was silenced,and in CRSwNP model mice,TIPE2 was overexpressed,followed by treatment with overexpressed TIPE2 combined with VD3.Western blot was used to measure the expression of TIPE2 and Arg-1,and ELISA was used to measure the expression of IL-4 and IL-13.RESULTS In the CRSwNP group,VD3 levels decreased,while TIPE2 and Arg-1 levels increased(all P<0.05).Arg-1 and TIPE2 were positively correlated(r2=0.994,P<0.05),and both were negatively correlated with VD3 levels(r2=0.652,P<0.05;r2=0.745,P<0.05).Silencing TIPE2 in J774A.1 cells led to a decrease in Arg-1,IL-4,and IL-13 levels(all P<0.05).In CRSwNP mice,overexpression of TIPE2 resulted in decreased VD3 and increased Arg-1,IL-4,and IL-13 levels,which were reversed by VD3 treatment(all P<0.05).CONCLUSION VD3 inhibits the expression of Arg-1,IL-4,and IL-13 in CRSwNP by downregulating TIPE2 expression.

Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.

Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

The stability of ammonium ion selective electrode is an important indicator to ensure accurate monitoring of ammonia nitrogen concentration in drinking water.However,in long-term monitoring process,interfering ions and water molecules in water samples may penetrate into the interior of the ammonium ion selective electrode to form a water layer,which affects the potential response and stability of the electrode.Perfluorooctanoic acid is a low surface energy material,and doping it in polyaniline can reduce surface energy of the composite and improve surface roughness.In this work,five ammonium ion selective electrodes were prepared by doping polyaniline with different concentrations of perfluorooctanoic acid as a solid contact layer,which made the solid contact layer of electrode had hydrophobic properties,thereby improving stability of the ammonium ion selective electrode.The stability of the ion-selective electrode was evaluated by potential drift experiment,and the optimal doping concentration of perfluorooctanoic acid in the sediment solution was determined to be 5 mmol/L.The experiment results showed that the solid contact layer had a water contact angle of 132o under the doping concentration,the potential drift rate was 41.66 μV/h,and potential drift rate in the aqueous layer test was 1.31 mV/h,which were all better than those of the unmodified electrode.The standard deviation of the electrode potential was 1.42 mV,which was obviously superior to that of the unmodified electrode.The characteristics of high stability of the electrode made it suitable for long-term monitoring of ammonia nitrogen content in water samples.

In the 1950s and 1960s,Japan's implementation of policies prioritizing economic develop-ment caused a lack of effective supervision over the discharge of industrial wastewater and exhaust gases,which led to the occurrence of the"Four Major Pollution Diseases",including Minamata disease,causing serious social and public health problems.To more effectively address public nuisances and pro-vide compensation to victims,the Japanese government gradually established an environmental damage compensation system with administrative relief characteristics since the 1970s.Through long-term prac-tice and system optimization,this system has evolved into a mature institutional framework with a clear division of labor and efficient collaboration.This paper systematically reviews the development process of Japan's environmental damage compensation system and deeply analyzes its legal frame-work and supporting policies,aiming to provide useful references for the construction and improve-ment of China's environmental damage compensation system.Meanwhile,through the case analysis of Minamata disease,the paper explores the specific mechanisms and effects in the compensation practices,further revealing the system's operational characteristics and implications,and providing a reference ba-sis for the construction of China's environmental governance legal system.