OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Pulmonary hypertension(PH)is a fatal disease characterized by pulmonary vascular remodeling,ultimately leading to right heart failure and death.Current treatments for PH are suboptimal,with no substantial improvement in overall survival among patients with advanced PH.Despite some progress in understanding the pathogenesis of PH,further studies at the molecular level are needed to develop more effective treatments for PH.Recent research has shown that long non-coding RNAs(lncRNAs)have an important regulatory function in the pathophysiological process of PH,and may thus be potential disease biomarkers and therapeutic targets.In this paper,we review recent progress in our understanding of the molecular mechanisms of lncRNAs in PH.

Purpose To construct an ultrasound molecular probe carrying miRNA-452/Let-7i and analyze its targeting effect on human induced pluripotent stem cell derived cardiomyocytes(hiPSCs-CMs)in vitro.Materials and Methods The biotinylated core lipid microbubbles(NBs),lipid microbubbles carrying adenovirus overexpressing miRNA-452/Let-7i(Ad-miR-452/Let-7i)and ultrasound molecular probes carrying adenovirus overexpressing miRNA-452/Let-7i and targeting protein MYH6(Ad-miR-452/Let7i-MYH6)were synthesized,and the expression rates of fluorescent proteins to verify their binding were compared.The physical and chemical properties,stability,and in vitro imaging of those abovementioned parameters were measured,respectively,and theirs biological safety was evaluated.hiPSCs-CMs was divided into Ad-miR-452/Let-7i group and Ad-miR-452/Let7i-MYH6 group,then theirs cell binding status were compared.Results The constructed NBs,Ad-miR-452/Let-7i and Ad-miR-452/Let7i-MYH6 had regular morphology and good stability.Detection data showed that theirs concentrations were(1.62±0.40)×108 particles/ml,(1.83±0.20)×108 particles/ml and(1.35±0.33)×108 particles/ml,respectively.The average particle sizes were(605.94±17.46)nm,(726.53±14.95)nm and(729.31±16.62)nm,respectively.The zeta potentials were(2.61±0.30)mV,(-11.21±0.71)mV and(-12.28±0.52)mV,respectively.The polydispersity indices were 0.24±0.07,0.26±0.14 and 0.25±0.13,respectively.With a concentration of 107 particles/ml,the imaging strengths of the three samples were 99.24±5.04,102.18±3.61 and 99.07±3.87,respectively.The miRNA-loaded ultrasound molecular probes exhibited no significant toxicity to the cells,with in vitro imaging lasting over 15 minutes,and they could specifically bind to hiPSC-CMs.Conclusion The constructed ultrasound molecular probe has stability and in vitro targeting,effectively improving virus transfection efficiency.

Objective To explore the predictive value of maximum standardized uptake value(SUVmax)and mean standardized uptake value(SUVmean)parameters in 18F-prostate specific membrane antigen-1007 positron emission tomography/computed tomography(18F-PSMA-1007 PET/CT)for the diagnosis and disease progression of prostate cancer(PCa).Methods Eighty patients with suspected PCa who underwent 18F-PSMA-1007 PET/CT examination in the hospital were selected and divided into the PCa group(49 cases)and the non-PCa group(31 cases)according to the biopsy pathological results.The 18F-PSMA-1007 PET/CT parameters were collected in the two groups of patients at admission,including SUVmax and SUVmean.The prostate specific antigen(PSA)and prostate cancer histological grade(GLEASON)score were also collected in patients of the PCa group at admission and 3 months after admission.The diagnostic efficiency of 18F-PSMA-1007 PET/CT parameters on PCa was analyzed by receiver operating characteristic(ROC)curve.The correlation between 18F-PSMA-1007 PET/CT parameters of patients in the PCa group at admission and PSA,GLEASON score was analyzed by Pearson method.Results The SUVmax and SUVmean in the PCa group were higher than those in the non-PCa group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of SUVmax and SUVmean were 0.887 and 0.843 respectively,the sensitivities were 80.65%and 83.87%,and the specificities were 87.76%and 73.47%respectively.The PSA and GLEASON score were lower 3 months after admission than those at admission in the PCa group(P＜0.05).Pearson correlation analysis showed that the SUVmax and SUVmean of patients in the PCa group at admission were positively correlated with PSA and GLEASON score at admission and 3 months after admission(P＜0.05).Conclusion SUVmax and SUVmean parameters of 18F-PSMA-1007 PET/CT have high predictive value for the diagnosis and disease progression of PCa.

Foot torsion stiffness refers to the foot's ability to resist deformation when subjected to torsional forces,and such characteristics play a crucial role in the prevention of sports injuries and design of athletic footwear.This review systematically summarizes the biomechanical research progress of foot torsion and shoe torsion,as well as the research and application of multi-segment foot models in foot-shoe torsion.The findings indicate that foot torsional stiffness significantly impacts lower limb kinematics,kinetics,and athletic performance.Optimizing this stiffness can improve stress distribution,reduce injury risk,and enhance performance.The future researches should focus on refining measurement techniques to enhance reliability and efficiency in clinical applications,providing a scientific foundation for sports injury prevention and footwear design.

Objective By analyzing the levels and distribution characteristics of whole blood metal exposure in four districts and counties in Xinjiang,a population baseline data was established to provide scientific basis for the development of environmental hygiene and health prevention and control intervention measures.Methods Using a stratified random sampling method,252 residents aged 3-80 were selected from four regions in Xinjiang(Altay City,Shuimogou District,Urumqi City,Wuqia County,and Zepu County).1ml of fasting venous blood was collected and the whole blood metal concentration was detected by inductively coupled plasma mass spectrometry(ICP-MS).SPSS21.0statistical software was used to analyze the differences in whole blood metal exposure levels.Results A total of 967 qualified samples were screened.Include metal elements with a detection rate of 75％for lead,manganese,and nickel in whole blood for analysis.Blood lead M(Q1,Q3)is 15.91(11.47,22.41)μg/L;blood manganese M(Q1,Q3)is 10.11(8.29,12.56)μg/L;blood nickel M(Q1,Q3)is 0.90(0.63,1.17)μg/L.There were statistically significant differences in the concentrations of blood lead,blood manganese,and blood nickel in different regions(H were 16.171,27.642,87.690,respectively,P＜0.05).There is a statisti-cally significant difference in blood nickel levels between urban and rural areas(H=19.261,P＜0.05).There were statistically signifi-cant differences in blood lead and blood manganese levels among different ages(H were 31.786,67.631,P＜0.05).There is a statisti-cally significant gender difference in blood lead and blood manganese levels(H were 31.255,19.921,P＜0.05).Conclusion Resi-dents in four districts and counties in Xinjiang have certain levels of internal exposure to lead,manganese,and nickel,and there are re-gional,urban-rural,and population differences.It is suggested that residents in Xinjiang may be at a potential risk of low-level expo-sure to multiple metals in the environment,and further research is needed.