Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Hydration status refers to the balance between the intake and discharge of water in the body. When the ingested and discharged water are roughly equal and the body is in water balance, it is the normal hydration status, and when the water intake is too little or too much, it is the "dehydration" or "overhydration status". The hydration status of the body not only affects metabolism, but also affects the functions of the urinary system, cardiovascular system, nervous system, etc. In order to further clarify the relationship between body hydration status and decompression sickness (DCS), this paper reviewed relevant studies and analyzed the interaction between hydration and decompression safety during diving. The primary causes of dehydration in diving are "hyperbaric diuresis", "immersion diuresis", breathing dry gas, heat, and cold. Dehydration not only promotes the occurrence of DCS but also reduces the aerobic work efficiency and athletic performance of divers, as well as affects cognition and mood. A study found that appropriate rehydration before and during diving can reduce the risk of DCS, which possibly associates with the increase of blood volume, plasma surface tension, and vasoconstriction. Fluid therapy is also important for those who already have DCS. This paper analyzed the amount, nature, timing, and effect of rehydration involved in the above links, comprehensively sorted out the relationship between hydration and diving safety, summarized the existing problems, and provided reference for practical application and future research.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

OBJECTIVE:At present,there are many reports on the related factors associated with the incidence of cervical spine instability in patients with rheumatoid arthritis,but there are problems such as small sample size and many confounding factors,and the research results of various studies on the same related factors are also different.This article analyzed the factors related to cervical spine instability in patients with rheumatoid arthritis by means of a systematic review. METHODS:Articles related to cervical spine instability in patients with rheumatoid arthritis were collected by searching both Chinese and English databases until March 2023.The outcome of cervical spine instability in patients with rheumatoid arthritis was used as the grouping criterion to abstract basic information,baseline patient characteristics,laboratory-related tests,medication use,and other relevant risk factors.Meta-analysis was done using Stata 14.0 software. RESULTS:(1)Sixteen relevant studies,all of moderate or above quality,were included,including seven studies with case-control studies and nine with cross-sectional studies.The overall incidence of cervical spine instability in patients with rheumatoid arthritis was 43.08%.(2)Meta-analysis showed:Related risk factors included female(OR=0.60,95%CI:0.44-0.82,P=0.002);age at disease onset(SMD=-0.52,95%CI:-0.86 to-0.18,P=0.003);duration of disease(SMD=0.58,95%CI:0.14-1.02,P=0.01);body mass index(OR=0.74,95%CI:0.63-0.88,P=0.001);rheumatoid factors positive univariate analysis subgroup(OR=1.33,95%CI:1.02 to 1.72,P=0.04),C-reactive protein(SMD=0.26,95%CI:0.16-0.35,P=0.00),erythrocyte sedimentation rate(SMD=0.15,95%CI:0.002-0.29,P=0.047),anti-cyclic-citrullinated peptide antibodies(OR=1.73,95%CI:1.19-2.51,P=0.004),28-joint Disease Activity Score(SMD=0.20,95%CI:0.04-0.37,P=0.02),destruction of peripheral joints(OR=2.48,95%CI:1.60-3.85,P=0.00),and corticosteroids(OR=1.91,95%CI:1.54-2.37,P=0.00)were strongly associated with the development of rheumatoid arthritis-cervical spine instability.Female and corticosteroid use were independently associated with the occurrence of rheumatoid arthritis-cervical spine instability. CONCLUSION:Based on clinical evidence from 16 observational studies,the overall incidence of rheumatoid arthritis-cervical spine instability was 43.08%.However,the incidence of cervical spine instability in rheumatoid arthritis patients varied greatly among different studies.Gender(female)and the use of corticosteroids were confirmed as independent correlation factors for the onset of cervical spine instability in patients with rheumatoid arthritis.The results of this study still provide some guidance for early clinical recognition,diagnosis,and prevention of rheumatoid arthritis-cervical spine instability.

The Major Principles of the Five Elements is a collection of Yin-Yang and Five Elements theories in the middle ancient period of China.The Xiangshu model of Yin-Yang and Five Elements is the basic paradigm to clarify the world and its existence."Constitution"and"Function"are a pair of important categories used in ancient philosophy to describe the relationship be-tween the nature and function of ontology.Based on the two temporal and spatial rhythms of the Heluo Heaven and Earth Five Elements view and the Jiugong Bafeng spatiotemporal view constructed by the Xiangshu model,The Major Principles of the Five Elements explains the connotation and characteristics of traditional medical constitution and function,aiming to elucidate the evolution process of the path-ogenesis of constitution and function,guide the dialectical thinking of constitution and function,and flexibly select and combine drug properties and flavors to harmonize the human constitution and function.This paper provides a unique perspective and method for ex-plaining the concept and connotation of constitution and function in traditional Chinese medicine by glimpsing the gradual changing way of thinking in traditional medicine from the Pre-Qin period to the Tang Dynasty.

Objectives:To observe the clinical efficacy of anterior cervical V-osteotomy Y-decompression and fusion(ACVYF)for treating ossification of posterior longitudinal ligament(OPLL)in cervical spine.Meth-ods:The clinical data of 60 patients with single-segment vertebral level OPLL who underwent surgical treat ment in Luoyang Orthopedic Traumatological Hospital of He'nan Province from June 2018 to October 2022 were retrospectively analyzed.Among them,30 cases were treated with ACVYF operation(ACVYF group),in-cluding 18 men and 12 women,aged 47-65 years(61.0±6.4 years),with a body mass index(BMI)of 16.8-28.1kg/m2(23.67±2.86kg/m2)and a disease duration of 10-80 months(37.5±20.1 months),whose surgical seg-ments fell in C3 in 2 cases,C4 in 5 cases,C5 in 13 cases,C6 in 10 cases.The other 30 cases were treat-ed with anterior cervical corpectomy decompression and fusion(ACCF)operation(ACCF group),including 19 men and 11 women,aged 44-68 years(59.5±6.8 years),with a BMI of 16.6-26.4kg/m2(23.30±2.56kg/m2)and a disease duration of 13-72 months(35.8±18.8 months),whose surgical segments fell in C3 in 3 cases,C4 in 6 cases,C5 in 12 cases,C6 in 9 cases.The two groups were comparable in gender,age,BMI,disease dura-tion,surgical section and other general information with no statistical difference(P＞0.05).The operation time,intraoperative bleeding,and complications of the two groups were compared;The cervical Japanese Or-thopaedic Association(JOA)scores were recorded before operation,at 1 week,and 3,6 and 12 months after operation,and the JOA score improvement rate was calculated at postoperative 12 months;The height of the fusion area and C2-7 Cobb angle were measured on X-ray films at pre-operation,1 week,3 months,6 months and 12 months after operation.The fusion condition of implants were observed and evaluated on X-ray film or CT image at 3 months,6 months and 12 months after operation.Results:The operation was completed smoothly in both groups.The operation time and intraoperative bleeding were 88.2±19.7min and 133.3±24.4mL respectively in the ACVYF group,which were 91.5+24.1min and 137.7±29.4mL in the ACCF group,and there was no statistical difference between the two groups(P＞0.05).Three cases of dysphagia occurred in both groups after surgery,which resolved spontaneously after 1-2 weeks.No complications occurred during the follow-up period,and there was no statistically significant difference in the complication rates between the two groups(P＞0.05).The JOA scores of both groups at all time points after surgery showed significant improvement compared with those before surgery(P＜0.05),and there was no statistically significant difference between the two groups at the same time points(P＞0.05);The height of the fusion zone and C2-7 Cobb angle after operation were statistically different from those before operation(P＜0.05),and no significant difference was found between the two groups at preoperation,postoperative 1 week and 3 months(P＞0.05),while those of ACVYF group were bigger than ACCF group at postoperative 6 and 12 months(P＜0.05).The improvement rate of cervical JOA score at 12-month follow-up was(72.39±10.54)％in the ACVYF group and(75.92±10.39)％in the ACCF group,and there was no statistically significant difference between the two groups(P＞0.05).The rate of implant fusion was better in the ACVYF group at 3-month and 6-month follow-ups(70.0％and 93.3％)than in the ACCF group(40.0％and 73.3％)(P＜0.05),and both groups had osseous fusion at 12 months postoperatively(P＞0.05).Conclusions:ACVYF can effectively relieve the compression of the posterior longitudinal ligament on the spinal cord at the vertebral level and improve the neurological function of the patients;Comparing with ACCF,ACVYF can better maintain the physiological curvature of the cervical vertebrae and speed up the fusion of the implants.

Objective To investigate the role of Taraxasterol(TAR)on ferroptosis in chondrocytes induced by Erastin.Methods The C28/I2 chondrocyte line was treated with Erastin to construct the ferroptosis model of chon-drocytes in vitro and the experiments were divided into Control,Erastin,TAR,and TAR+Erastin groups.Cell via-bility was detected by the CCK-8 assay.Cytotoxicity was detected by the lactate dehydrogenase(LDH)kit and the Calcein/PI cytokinesis kit.Flow cytometry was used to detect lipid reactive oxygen species(ROS).The intracellular glutathione(GSH)content was detected by GSH kit.Mitochondrial membrane potential was detected by JC-1 stai-ning and RH123 staining.ACSL4 and GPX4 protein expression and the key indicators of ferroptosis were detected by Western blot.Results TAR restored the decreased cell viability of C28/I2 chondrocytes induced by Erastin treatment as well as reduced Erastin-induced cytotoxicity(P＜0.01).Compared with the control group,the level of intracellular lipid ROS increased(P＜0.01)and the content of GSH decreased(P＜0.01)after treatment with Erastin,while TAR could reduce the production of lipid ROS(P＜0.01)and increase the content of GSH(P＜0.01).TAR restored mitochondrial membrane potential in C28/I2 chondrocytes ferroptosis,decreased ACSL4 pro-tein expression(P＜0.01)and increased GPX4 protein expression(P＜0.01).In addition,TAR restored the re-duced cell viability caused by IL-1 β treatment.Conclusion TAR can inhibit Erastin induced ferroptosis in C28/I2 chondrocytes,which may be related to the regulation of ACSL4 and GPX4 protein expression.

Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P＜0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P＜0.01)and the level of ROS(F=52.99,P＜0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P＜0.05),p-PKCα(F=24.56,P＜0.05)and HIF-1α proteins(F=6.85,P＜0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.

Lower cervical fracture and dislocation combined with facet interlocking is an acute spinal cord injury caused by flexion-distraction and rotational force. It can result in various degrees of quadriplegia and urinary and defecation disorders, with a high rate of disability, most of which requires surgical treatment. Surgical treatment options for lower cervical fracture and dislocation combined with facet interlocking include anterior approach, posterior approach and combined surgical approach. However, the optimal treatment option remains to be determined. The anterior approach, with the advantages of simple access, smaller trauma, fewer complications, and good sagittal balance, is currently the preferred treatment option for lower cervical fracture and dislocation combined with facet interlocking. Many methods of surgical repositioning and fixation are available in anterior approach, but the choice of surgical repositioning and fixation options in anterior approach is still controversial among scholars. For this purpose, the authors reviewed the progress of researches on anterior surgical approach for lower cervical fracture and dislocation combined with facet interlocking, aiming to provide a reference for its clinical treatment.