BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

By analyzing the understandings of water points (acupoints connected with the kidney) and its association with water (kidney), zangfu organs and meridian-collateral recorded in Suwen: Shuire Xue Lun (Discussion on Water and Heat Diseases in Plain Question), it is found that the recognition on the water points is different from that on water diseases in Huangdi Neijing (the Yellow Emperor 's Inner Classic). The recognition on the water points focuses on the core theory, "rooted at the kidney", to explain the water diseases. Besides, in association with the study on the connotation of "luo" in Huangdi Neijing, it is discovered that "yinluo" discussed in water points is actually the misunderstanding of "zang zhi yinluo" that means "the connection by the kidney". It is shown that the discussion of water points refer to the elaboration of zangfu organs and 57 acupoints connected with water (the kidney), rather than the theory of collaterals. The characteristics of these 57 acupoints involved and the related needling techniques provide a new approach to the treatment of zangfu diseases.
Acupuncture Points ; Humans ; Meridians ; China ; History, Ancient ; Medicine in Literature ; Medicine, Chinese Traditional/history* ; Acupuncture Therapy/history*

The diseases and pathological manifestations associated with chongmai (thoroughfare vessel) are the representative in the practical applications of chongmai theory. Elucidating this theory serves as a prerequisite of acupuncture and moxibustion therapy. Based on literature analysis, the diseases and clinical manifestations of chongmai recorded in the time of Huangdi Neijing (The Yellow Emperor's Inner Classic) were analyzed so as to reinterpret the diagnostic process, pathological characteristics, and clinical manifestations of disorders, and evaluate the value of chongmai theory. Chongmai diseases were identified from the palpation initially, known as the "palpation on abdominal pulse". The "qi reversion" of chongmai represents a typical clinical manifestation of chongmai diseases, such as ji (abdominal mass), jia (abdominal hematoma), and shan (hernia), occurring in different sites of the abdomen and in different pathological stages. A part of distribution of chongmai is considered in clinical manifestation, diagnosis and treatment of acupuncture and moxibustion. To emphasize the significance of chongmai in modern acupuncture-moxibustion theory and practice, the diagnostic and therapeutic patterns of the related disorders should be considered in clinical practice. The characteristics of chongmai are reflected in three aspects: qi, blood and abdomen, which are determined by both its inherent properties and the clinical manifestations of related diseases.
Humans ; Acupuncture Therapy ; Moxibustion ; History, Ancient ; Meridians ; Medicine, Chinese Traditional

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective To establish a mouse model of liver aging induced by irradiation combined with hepatectomy.Methods A model was established via single irradiation combined with hepatectomy.The survival rate,body weight,liver index and liver function of the mice were detected.The expressions of senescence-associated secretory phenotype factors in serum were detected with enzyme-linked immunosorbent assay(ELISA)and flow cytometry.The mRNA levels of senescence-associated secretory phenotype factors and telomerase in liver tissue were detected by real-time quantitative PCR(qPCR).The expressions of cyclin dependent kinase inhibitor 1A(CDKN1A)and cyclin dependent kinase inhibitor 2A(CDKN2A)were determined by Western blotting.ELISA was used to calculate senescence-associated β-galactosidase(SA-β-Gal)and lipofuscin levels.Tissue malondialdehyde levels were measured using the thiobarbituric acid(TBA)method.The size of hepatocyte nuclei and lipid accumulation were detected by hematoxylin-eosin(HE)stainingand oil-red-O while triglyceride levels in the liver were studied with the weighing method.Results After irradiation combined with hepatectomy,the body weight of mice was significantly reduced,the liver index was not significantly affected,but the transaminase level was significantly increased.The levels of SA-β-Gal and lipofuscin increased while telomerase activity decreased significantly,and the nucleus size increased.The expressions of cyclin dependent protein kinase inhibitors CDKN1A and CDKN2A increased.The levels of senescence-associated secretory phenotype factors were significantly increased.Hepatic lipid deposition and oxidative damage were aggravated.Conclusion A mouse model of liver aging induced by irradiation combined with hepatectomy has been established.

The fundamental pathogenic mechanisms of inflammatory bowel disease(IBD),a chronic inflammatory illness affecting the gastrointestinal tract,are still not fully understood.Dipeptidyl peptidase Ⅳ(DPP-4)is a glycoprotein found on the cell surface that has signaling and enzymatic properties.In addition,there is growing evidence from animal models and clinical trials that DPP-4 inhibitors have potential impacts beyond only lowering blood sugar levels,such as immunomodulatory and anti-inflammatory capabilities.This article reviews the biological properties of DPP-4 and its research progress in the diagnosis and treatment of IBD.It also discusses the mechanism of DPP-4 in IBD,aiming to provide a more in-depth understanding of the role of DPP-4 in IBD.

BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Eye diagnosis is a method for inspecting systemic diseases and syndromes by observing the eyes.With the development of intelligent diagnosis in traditional Chinese medicine(TCM),artificial intelligence(AI)can improve the accuracy and efficiency of eye diagnosis.However,the research on intelligent eye diagnosis still faces many challenges,including the lack of standardized and precisely labeled data,multi-modal information analysis,and artificial in-telligence models for syndrome differentiation.The widespread application of AI models in medicine provides new insights and opportunities for the research of eye diagnosis intelli-gence.This study elaborates on the three key technologies of AI models in the intelligent ap-plication of TCM eye diagnosis,and explores the implications for the research of eye diagno-sis intelligence.First,a database concerning eye diagnosis was established based on self-su-pervised learning so as to solve the issues related to the lack of standardized and precisely la-beled data.Next,the cross-modal understanding and generation of deep neural network models to address the problem of lacking multi-modal information analysis.Last,the build-ing of data-driven models for eye diagnosis to tackle the issue of the absence of syndrome dif-ferentiation models.In summary,research on intelligent eye diagnosis has great potential to be applied the surge of AI model applications.