Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

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.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective: To investigate the expression and potential role of heterogeneous nuclear ribonucleo-protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma. Methods: The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A-IP-qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells. Results: The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment. Conclusions HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up-regulated at transcriptional level but obviously down-regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin-proteasome pathway may account for the down-regulation of HNRNPA2B1 at protein level.

Objective To investigate the expression and potential role of heterogeneous nuclear ribonucleo?protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma. Methods The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A?IP?qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells. Results The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment. Conclusions HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up?regulated at transcriptional level but obviously down?regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin?proteasome pathway may account for the down?regulation of HNRNPA2B1 at protein level.

Objective To investigate the clinical characteristics of children with medulloblastoma (MB). Methods The correlations amongst MB histopathological subtype,age at diagnosis,gender,primary tumor locations, relapsed tumor and relapsed tumor locations were analyzed retrospectively in 83 children who were diagnosed as MB by histopathology subtypes from February 2012 to April 2015 in Beijing Shijitan Hospital Affiliated to Capital Medical Uni-versity.The data was conducted by using SPSS 22.0 statistical software.Results Among the 83 cases (53 boys and 30 girls),there were 14 patients younger than 3 years old (9 boys and 5 girls)and 69 patients (44 boys and 25 girls)ol-der than 3 years old,including 28 relapsed (19 boys and 9 girls)and 55 non -relapsed cases (34 boys and 21 girls). The median age was 80.2 (13.1 -184.7)months at diagnosis.Of these 83 cases,48.2% (40 /83 cases)was classic medulloblastoma (CMB)(2 cases less than 3 years old),24.1 % (20 /83 cases)was desmoplastic /nodular medullo-blastoma (DMB)(6 cases less than 3 years old),12.1 % (10 /83 cases)was large cell/anaplastic medulloblastoma (LC /AMB)(1 case less than 3 years old),3.6% (3 /83 cases)was extensive nodular medulloblastoma (MBEN)(1 case less than 3 years old),and 12.1 % (10 /83 cases)(3 cases less than 3 years old)was mixed subtype.The rela-tionships between age at diagnosis and histopathological subtype,gender and primary tumor location were all statistically significant (χ2 =0.014,0.013,all P <0.05).Conclusions The incidence of boys with MB is higher than girls.CMB is the main histopathologic subtype in children over 3 years old.The primary tumor location involving the cerebellar vermis or cerebellar vermis and the fourth ventricle is higher in girls with MB.The primary tumor location involving the fourth ventricle,the fourth ventricle and other parts of the central nervous system,Cerebellar vermis and other parts of the central nervous system or other parts of the central nervous system is higher in boys with MB.

Objective To explore the clinical prognostic value of rapid detection for plasma NT-proBNP levels on admission in patients with acute myocardial infarction.Methods 56 patients with AMI were measured plasma NT-proBNP imediately in hospital,and then they were divided into A,B and C group according to NT-proBNP levels (A group:＜ 500ng/L,B group:500-2 000ng/L,C group:＞ 2 000ng/L).The incidence of major adverse cardiac events (MACE including congestive heart failure,malignant arrhythmia,cardiogenic shock and sudden cardiac death) in subjects were observed respectively during hospitalisation and 30 days.Results The three group subjects with different NT-proBNP levels presented different incidence of MACE(A group:1,0;B group:3,1;C group:8,6) at duration of hospital stay,30days (x2 =6.705,P =0.035 ; x2 =7.957,P =0.008).With the NT-proBNP levels rising in AMI paitents,the inciedence of MACE increased.The incidence of MACE in A,B and C group were 6.6％,18.18％ and 73.69％ respectively.Conclusion In AMI patients,plasma NT-proBNP levels could predict early MACE incidence,which has an important value to evaluate the early clinical prognosis.

Objective To investigate the relationship between elderly male patients with coronary heart diseases (CHD) and endogenous androgen level and other related factors.Methods 28 male patients with acute coronary syndrome (ACS) were chosen as research group,28 male patients with stable angina pectoris (SAP) were chosen as observation group,and 28 healthy male people were selected as control group.All of three groups were checked by carotid artery Doppler ultrasonography and the peripheral blood concentration of testosterone (T),TC,LDL-C,Glu,CRP were measured,BMI was calculated in all three groups.Results Peripheral blood concentration of T,TC,LDL-C,Glu in ACS group and SAP group were significantly higher than those of the control group(P ＜0.05).IMT and number,quality of plaque in patients with ACS and SAP were significantly different compared with the control group (P ＜ 0.05).T,Tc,LDL-C,CRP,BMI,IMT,unstable plaque were significantly different between ACS group and SAP group(P ＜ 0.05).Glu had no statistical difference between ACS group and SAP group (P ＞ 0.05).Conclusion Peripheral blood concentration of T was negatively correlated with arterosclerosis,unstable plaque,Tc,LDL-C,BMI in old male CHD patients

Objective To investigate the clinical characteristics and current condition of treatment for systemic lupus erythematosus (SLE) associated pulmonary arterial hypertension (PAH).Methods 10-year inpatients cases were reviewed and followed up.Cases were divided into 2 groups:group A:patients with baseline pulmonary arterial systolic pressure (PASP) lower than 70 mmHg； group B:patients with baseline PASP higher than 70 mm Hg.Pearson's correlation analysis,Chi-square test,Logistic regression,Cox-Mantel and Wilcoxon test were used for statistical analysis.Results There were totally 155 cases with 184 records of admission which accounted for 4.16％ among total lupus cases.The main clinical characteristics included Raynaud's phenomenon (47.3％),pericardial effusion (41.9％) and high titer of anti-RNP antibody (55.4％).There were 132 cases enrolled for prognostic statistical analysis.There were 47 cases of death (35.6％) in total,among which 9 cases (19.1％) were in group A and 38 cases (80.9％) were in group B.In group A,there was a positive correlation between PASP and lupus disease activity index score.Single therapy analysis by Chi-square test showed that cyclophosphamide (CTX) (P＜0.05) and PAH targeted drugs (P＜0.01) were significantly associated with favorable outcome but logistic regressive analysis only confirmed the efficacy of target drugs (P＜0.01).PAH target drugs significantly improved the one year survival rate of the severe cases.Conclusion The main clinical characteristics of SLE associated PAH include Raynand's phenomenon,pericardial effusion and positive anti-RNP antibody.The severity of PAH may not be related to lupus disease activity.PAH targeted drugs are effective in SLE-PAH.CTX may be effective in some cases.For severe cases,the combination therapy of CTX and PAH targeted drugs could significantly improve the prognosis.

Objective To explore the clinical value of plasma NT-proBNP in evaluation of major adverse cardiac event in chronic heart failure patients.Methods 120 chronic heart failure patients who measured plasma NT-proBNP were divided into two groups according to median plasma NT-proBNP level (A group:≤ median,B group:＞ median).The incidence of major adverse cardiac events,MACE(including malignant ventricular arrhythmia and sudden cardiac death) were observed during hospitalization.Results The left ventricular end-diastolic diameters (LVEDDs) in B group was longer than that in A group [(58.80 ± 6.90) mm vs (54.32 ± 8.00) mm,P =0.035)],and the left ventricular ejection fraction(LYEF) in B group was lower than that in A group[(29.16 ± 8.31) ％ vs (33.80 ± 6.90)％,P =0.037].The incidence rate of major adverse cardiac events in A group was higher than that in B group (11.63％ vs 1.67 ％,P ＜ 0.05).The multivariate Logistic regression analysis showed that the NT-proBNP level in chronic heart failure inpatients was independently associated with major adverse cardiac event during hospitalization(OR =5.28,95％ confidence intervals 3.54 ～9.26,P＜0.05).Conclusion In chronic heart failure patients,plasma NT-proBNP level could predict the MACE incidence during hospitalization,and have important value to evaluate the prognosis of chronic heart failure.