OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

OBJECTIVE:Patients with osteoporotic vertebral compression fractures still have residual back pain after vertebral augmentation.The current research is characterized by limited sample size,complex confounding factors,and inconsistent research results.To gain a deeper understanding of this phenomenon,the aim of this study was to identify and evaluate the risk factors for residual back pain after surgery through a systematic review and meta-analysis.METHODS:A comprehensive search was conducted in CNKI,VIP,WanFang,CBMdisc,PubMed,The Cochrane Library,Embase,and Web of Science for case-control studies on residual back pain after vertebral body augmentation for osteoporotic vertebral compression fractures from database inception to July 2024.The search terms were a combination of subject terms and free terms.The basic information,patient characteristics,surgical-related indicators,and risk factors for surgical back pain of the included studies were extracted.After evaluating the bias risk of all included studies,a meta-analysis was conducted using Stata 14.0 software on the relevant indicators.RESULTS:(1)21 case-control studies with a total of 8 043 patients were included.Among them,965 patients developed back pain.The quality score of all 21 studies was ≥7.(2)The meta-analysis results showed that age(WMD=0.98,95％CI:0.40-1.56,P=0.010),bone mineral density(WMD=-0.28,95％CI:-0.34 to-0.21,P=0.000),the number of vertebral fractures(OR=3.50,95％CI:2.65-4.62,P=0.000),thoracolumbar fracture index(OR=3.65,95％CI:2.61-5.11,P=0.000),cement volume(OR=6.89,95％CI:2.62-18.17,P=0.000),and cement distribution(OR=2.38,95％CI:1.93-2.93,P=0.000)were risk factors for the development of back pain after vertebral body augmentation in patients with osteoporotic vertebral compression fractures.CONCLUSION:Current evidence indicates that age,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,bone cement injection volume,and the distribution of bone cement are risk factors for low back pain.Specifically,bone mineral density,the number of vertebral fractures,thoracolumbar fracture index,and non-uniform distribution of bone cement are identified as independent risk factors for low back pain.Patients exhibiting these high-risk factors require vigilant monitoring and prompt intervention to mitigate the occurrence of clinical low back pain,thereby enhancing patient outcomes and quality of life.

Osteoporosis is a systemic disease, and epidemiological projections indicate that by 2050, approximately 23.43% of the Chinese population over 50 years of age will be affected. Given the poor prognosis associated with osteoporosis, the exploration of safe and effective natural products is of considerable significance. Studies investigating the chemical constituents of traditional Chinese medicine in cellular and/or animal models have demonstrated bone-protective effects. Although most of these compounds lack clinical data, they hold considerable potential as lead candidates for drug development. In-depth study of the structure-activity relationship of these natural products not only contributes to elucidating the mechanisms of action but also provides a theoretical basis for the development of novel antiosteoporosis therapies. This review summarizes natural products with potential antiosteoporotic effects reported between 2020 and 2024. Overall, plant-derived natural compounds exhibit antiosteoporotic effects by regulating bone remodeling, inflammation, and oxidative stress, highlighting their promise as multitarget therapeutic candidates.

ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

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.

Objectives:To systematically evaluate the incidence and risk factors of titanium mesh subsidence following anterior cervical corpectomy and fusion(ACCF),and to explore the clinical impact of titanium mesh subsidence.Methods:Databases including CNKI,WangFang,VIP,China Biology Medicine disc(CBM),PubMed,Embase,Cochrane Library,and Web of Science were searched for case-control and cohort studies published from the inception of each database to June 2024 about the risk factors of titanium mesh subsi-dence following ACCF.The Newcastle-Ottawa scale(NOS)was used to assess the quality of the included studies.Basic information(first author,publication year,study type,definition of subsidence,assessment time,sample size,number of subsidence cases,and subsidence incidence),reported risk factors(age,sex,BMI,sur gical segment,number of surgical segments,smoking,hypertension,diabetes,fusion segment height,C2-7 Cobb angle,segment angle,vertebral body quality,titanium mesh tilt angle,titanium plate type,screw-plate angle,and titanium mesh placement),cervical JOA score,JOA score improvement rate,and fusion rate were extracted and analyzed using Stata 18.0 software for meta-analysis.Results:A total of 16 studies were in-cluded,and all were case-control studies with NOS scores ≥7.A total of 1562 patients were included,with 555 cases of titanium mesh subsidence.The meta-analysis showed that the incidence of titanium mesh subsi-dence after ACCF was 37％.Risk factors for titanium mesh subsidence included older age[MD=2.680,95％CI(1.228,4.132),P=0.000],female[OR=0.71,95％CI(0.56,0.90),P=0.004],smoking[OR=1.924,95％CI(1.108,3.342),P=0.020],osteoporosis[MD=-62.997,95％CI(-86.670,-39.323),P=0.000],a big number of surgical seg-ments[OR=0.096,95％CI(0.054,0.172),P=0.000],posterior placement of titanium mesh[MD=0.743,95％CI(0.605,0.968),P=0.026],excessive intervertebral distraction[MD=1.317,95％CI(0.752,1.881),P=0.000],seg-ment angle(titanium mesh expansion angle)[MD=0.887,95％CI(0.117,1.657),P=0.024],and a big titanium mesh tilt angle[MD=4.475,95％CI(1.725,7.225),P=0.001].Titanium mesh subsidence was associated with a decrease in cervical JOA score[MD=-0.542,95％CI(-0.947,-0.137),P=0.009],JOA score improvement rate[MD=-11.003,95％CI(-15.315,-6.691),P=0.000],and cervical fusion rate[OR=3.003,95％CI(1.019,8.854),P=0.046].Conclusions:The current evidence indicates that older age,female,smoking,osteoporosis,a big number of surgical segments,posterior placement of titanium mesh,excessive intervertebral distraction,and big titanium mesh expansion angle(segment angle)and titanium mesh tilt angle are the risk factors for titanium mesh subsidence after ACCF.Cage subsidence after ACCF can impair intervertebral fusion and reduce the overall effectiveness of the surgery,and therefore warrants careful clinical attention.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To analyze the clinical characteristics of anti-melanoma differentiation associated gene 5 (MDA5) antibody-positive juvenile dermatomyositis (JDM) patients.Methods:A retrospective case-control study was conducted. The positive group included 18 children with anti-MDA5 antibody-positive JDM who were admitted to the Department of Rheumatology and Immunology at Capital Center for Children′s Health with Capital Medical University between January 2016 and January 2023. Another 36 children with anti-MDA5 antibody-negative JDM hospitalized during the same period were enrolled as the negative group. Based on the extent of pulmonary involvement and pulmonary CT scores, the MDA5-positive group was further divided into severe pulmonary involvement and non-severe pulmonary involvement subgroups. Chi-square test and Kruskal-Wallis test were used to compare clinical features, laboratory test results between groups.Results:Among the 18 patients in the MDA5-positive group, 7 were male and 11 were female, with an age of onset of 5.0 (2.6, 9.4) years and disease duration of 6.0 (4.0, 9.3) months. The MDA5-negative group included 36 cases (14 male, 22 female), with an age of onset of 4.9 (2.0, 7.0) years and disease duration of 5.0 (1.8, 7.0) months. The MDA5-positive group exhibited significantly higher rates of arthritis, skin ulcers, and interstitial lung disease (ILD), along with elevated serum ferritin (SF) and erythrocyte sedimentation rate levels compared to the MDA5-negative group (9/18 vs. 11% (4/36), 6/18 vs. 3% (1/36), 16/18 vs. 33% (12/36), 327 (141, 518) vs. 131 (68, 257) μg/L, 17.5 (12.5, 26.8) vs. 11.0 (5.0, 13.0) mm/1 h, χ2=7.92, 7.41, 14.84, Z=2.50, 2.87, all P<0.05). Conversely, the MDA5-positive group had lower rates of muscle weakness and lower creatine kinase levels (5/18 vs. 75% (27/36), 58.5 (49.3, 97.5) vs. 225.0 (68.0, 695.5) U/L, χ2=11.08, Z=-2.94, both P<0.05). Severe pulmonary involvement 6 cases and non-severe pulmonary involvement subgroups 12 cases. Among the MDA5-positive patients, those in the severe pulmonary involvement subgroup had an older age at onset and higher rates of muscle weakness as well as hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), SF, and Krebs von den Lungen-6 (KL-6) compared to the non-severe subgroup (all P<0.05). In the MDA5-positive group, 17 patients improved after treatment with glucocorticoids combined with immunosuppressants, while One died due to rapidly progressive ILD. Conclusions:Anti-MDA5 antibody-positive JDM is characterized by typical skin rashes, a high incidence of arthritis and skin ulcers, relatively mild muscle involvement, but is prone to ILD. Among MDA5-positive patients, those with older age at onset, muscle involvement (manifested as muscle weakness and elevated muscle enzymes (LDH, HBDH)), or significantly elevated KL-6 and SF levels are more likely to develop severe pulmonary complications.