Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
Humans ; Cellular Senescence/physiology* ; Musculoskeletal Diseases/pathology* ; Aging/pathology* ; Animals ; Senescence-Associated Secretory Phenotype/physiology* ; Sarcopenia ; Osteoporosis

Objective To explore the sensitizing effect of manganese for radiotherapy against tumors and its possible mechanisms.Methods A total of 300 male C57BL/6 mice(6～8 weeks old,weighing 20～23 g)with subcutaneous tumor were randomly divided into 4 groups:control group,radiotherapy group,manganese treatment group,and combined radiotherapy and manganese treatment group.Nasal drip with 10 μg manganese adjuvant was applied to the mice from the latter 2 groups on day 9 of tumor bearing,then single dose of 20 Gy radiation was locally administered on day 10.Tumor growth and mouse survival were monitored regularly.The sensitizing effect of manganese on radiotherapy was determined by monitoring and comparing the tumor growth among different unilateral mouse models.Bilateral tumor-bearing model was used to examine the effect of manganese on abscopal effects induced by radiotherapy.Flow cytometry was used to illustrate the changes in tumor-infiltrating immune cells in unilateral tumor bearing model.Immunohistochemical staining was employed to evaluate the spleen function in unilateral tumor bearing mice.Results Based on repeated validation of 3 different unilateral tumor-bearing models,radiotherapy combined with manganese therapy significantly inhibited tumor growth and prolonged survival of mice(P＜0.05).The results of bilateral tumor-bearing model showed that manganese therapy enhanced abscopal effects of radiotherapy,and significant regression was observed in both side of tumor under radiotherapy or not(P＜0.05).Flow cytometry revealed that manganese further increased radiation-induced CD8+T infiltration(P＜0.05)and decreased radiation-induced infiltration of Treg cells and myeloid-derived suppressor cells(MDSCs)(P＜0.05).Furthermore,manganese increased lymphocyte reserve pool of the spleen and improved its function.Conclusion Manganese adjuvant could act as a sensitizing agent for radiotherapy,by improving the function of spleen and reprogramming the tumor microenvironment synergistically.

Objective To establish an animal model and evaluation system for lymph node metastasis of breast cancer.Methods A total of 60 female BALB/c mice(6～8 weeks old)were subjected,and then 6 models of lymph node metastasis(n=10)were constructed through injection at different parts in the mice with cell suspension of 4T1 breast cancer cells.Transgenic mice(n=5)of mouse mammary tumor virus-polyoma middle T antigen(MMTV-PyMT)were employed and served as model of spontaneous tumor metastasis.Then the advantages and disadvantages of different lymph node metastasis models were comprehensively evaluated from multiple aspects,such as operability,histomorphology and pathological detection,tumor growth rate and mouse survival.Results Among the 7 metastasis models,4 models of lymph node metastasis were successfully established.Among them,the PyMT mouse spontaneous tumorigenesis model showed the best clinical reproduction,with a tumorigenesis rate of up to 100％,but had a disadvantage of poor experimental standardization.The hind paw-popliteal lymph node model had the fastest lymph node metastasis,easy operation and high repeatability,and a tumorigenesis rate of 100％,indicating its suitable for lymph node metastasis related research.The thigh subcutaneous-inguinal lymph node model also successfully simulated lymph node metastasis,with simple operation and high repeatability,a tumorigenesis rate of up to 100％,but its metastasis time was slightly longer than the hind paw-popliteal lymph node model.The inguinal lymph node-contralateral lymph node model was also a successful lymph node metastasis model,but with difficult operation,only 50％tumor-bearing rate,and poor repeatability.Lymph node metastasis model was not successfully established in the other 3 tumor-bearing models(under the tongue-internal jugular scapular tongue muscle lymph node model,bone marrow-inguinal lymph node model and right upper back skin-axillary lymph node model)in a short time,with no tumor cells observed in the pathological sections.Conclusion Through the comprehensive comparison of multiple models,mouse hind paw-popliteal lymph node model is the most suitable for conducting related research.

Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

GI (GIGANTEA) is one of the output key genes for circadian clock in the plant. The JrGI gene was cloned and its expression in different tissues was analyzed to facilitate the functional research of JrGI. RT-PCR (reverse transcription-polymerase chain reaction) was used to clone JrGI gene in present study. This gene was then analyzed by bioinformatics, subcellular localization and gene expression. The coding sequence (CDS) full length of JrGI gene was 3 516 bp, encoding 1 171 amino acids with a molecular mass of 128.60 kDa and a theoretical isoelectric point of 6.13. It was a hydrophilic protein. Phylogenetic analysis showed that JrGI of 'Xinxin 2' was highly homologous to GI of Populus euphratica. The result of subcellular localization showed that JrGI protein was located in nucleus. The JrGI, JrCO and JrFT genes in female flower buds undifferentiated and early differentiated of 'Xinxin 2' were analyzed by RT-qPCR (real-time quantitative PCR). The results showed that the expression of JrGI, JrCO and JrFT genes were the highest on morphological differentiation, implying the temporal and special regulation of JrGI in the differential process of female flower buds of'Xinxin 2'. In addition, RT-qPCR analysis showed that JrGI gene was expressed in all tissues examined, whereas the expression level in leaves was the highest. It is suggested that JrGI gene plays a key role in the development of walnut leaves.
Juglans/genetics* ; Phylogeny ; Plant Leaves ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

OBJECTIVE To prepare and evalu ate doxorubicin-loaded red blood cell membrane chitosan-targeted nanoparticles of targeting tumor cell folate acid （FA）receptor（FA-RBC-DOX-CS-NPs）. METHODS Doxorubicin-loaded chitosan nanoparticles （DOX-CS-NPs） were prepared by ion cross-linking method. FA and amino polyethylene glycol phospholithin （NH2- PEG2000-DSPE）were covalently linked to modify the red blood cell membrane to construct FA-RBC-DOX-CS-NPS. FA-RBC- DOX-CS-NPs were characterized and investigated on in vitro drug release characteristics ，antitumor activity and endocytosis ability （investigation with human breast cancer MCF- 7 cells）. RESULTS Average particle size of FA-RBC-DOX-CS-NPs was （254.200± 2.651）nm，and polydispersity index was 0.199±0.031；Zeta potential was （－10.100±0.213）mV. FA-RBC-DOX-CS-NPs released fast in the tumor microenvironment （pH6.5）. Cellular experiments showed that ，the nanoparticles could inhibit the activity of MCF- 7 cell proliferation and improve the efficiency of endocytosis. CONCLUSIONS FA-RBC-DOX-CS-NPs are prepared successfully. The nanoparticles have good tumor cell targeting and endocytosis ability ，and can realize the enrichment of drugs in tumor cells.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

Objective:To investigate the risk factors related to the hemodynamic instability occurring after carotid artery stenting(CAS) in elderly patients with carotid artery stenosis.Methods:The clinical data of 80 patients with carotid artery stenosis, who were treated with CAS at Xuanwu Hospital, Capital Medical University during the period from January 2018 to Decmber 2018, were retrospectively analyzed. Record demographic characteristics (age, gender, height, weight), history of underlying diseases (hypertension, diabetes, kidney disease, heart failure, etc.), history of medications, etc. Observe the clinical parameters such as creatinine, blood urea nitrogen (BUN), urine volume, input and output, albumin, hemoglobin, location of stenosis, and degree of stenosis. Measurement data conforming to the normal distribution were expressed as the mean ± standard deviation ( Mean± SD), and the t-test was used for comparison between groups; the measurement data that does not conform to the normal distribution were expressed as the median (interquartile range) [ M( P25, P75)] indicates that the rank sum test was used for comparison between groups; the Chi-square test was used for comparison of count data between groups. Relevant variables were subjected to single factor analysis, and statistically significant indicators were selected according to the results of single factor analysis to be included in the multivariate Logistic regression analysis. Results:After CAS, a total of 37 patients among the 80 patients developed hemodynamic instability, the incidence rate was 46.25%. Univariate analysis indicated that the factors associated with the occurrence of postoperative hemodynamic instability included height , platelet count, ulceration plaque and the fluid intake in the first 24 hours after surgery; Multivariate regression analysis revealed that the presence of ulceration plaque ( OR=11.559, 95% CI: 1.232-108.495) and the fluid intake in the first 24 hours after surgery( OR=1.001, 95% CI: 1.000-1.001) were the independent risk factors related to the hemodynamic instability after CAS. Conclusion:Elderly patients with the presence of ulceration plaque before surgery are more likely to develop hemodynamic instability after CAS, and within 24 hours after surgery is a high-risk time period for hemodynamic instability.

Chinese herbal medicines( CHMs) are a class of preparations made from natural plants that pose health beneficial properties as well as illness prevention functions. Thanks to a panel of salutary features,such as comprehensive immunological enhancement and inhibition of pathogenic bacteria,negligible side-effects,inappreciable drug-resistance,CHMs have been taken as one of the costeffective candidates for antibiotics substitutions. Through probiotics fermentation,the enzymatic hydrolysis of matrixes of CHMs enables easier release of the active ingredient as well as endows less toxicity of the preparations derived. During fermentation,the macromolecule or polymers forms of the active ingredient can be cut down to smaller molecule,which favors the transmembrane transport and improve adsorption of the active ingredients by the tissues. Other than the enzymatic benefits,probiotics can produce metabolites that inhibit pathogenic bacteria propagation,which may function synergically with the inhibitory effects of the CHMs preparations to fight the target pathogens. In addition,the oligosaccharide like components of CHMs can promote the growth of probiotics in intestinal environment which may largely facilitate the gut health. To summarize,the fermentation of CHMs using probiotics brings about the biochemical reactions and elevates the health beneficial effects by synergy of the microbial and herbal activities. It has been proved to be one of promising approaches as to antibiotic substitutions,particularly in livestock and poultry breeding industries. This review covered the recent progress of CHMs fermentation on the aspects of microbial strains,patterns of fermentation and active substances from fermentation of CHMs and their potency,respectively.
Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; Fermentation ; Humans ; Research