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*

OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group， model group， quercetin high-dose， medium-dose and low-dose groups （40， 20， 10 μmol/L）， and positive control group （cyclosporine A， 1 μmol/L）. Reactive oxygen species （ROS）， mitochondrial membrane potential （MMP）， openness of mitochondrial permeability transition pore （MPTP）， adenosine triphosphate （ATP）， malondialdehyde （MDA）， lactate dehydrogenase （LDH） and creatine kinase （CK） were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group， model group， quercetin high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg）， and positive control group （trimetazidine， 6.3 mg/kg）， with 8 rats in each group. They were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last medication， myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH， MDA， creatine kinase isoenzyme-MB （CK-MB）， superoxide dismutase （SOD）， complex Ⅰ， complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group， ROS fluorescence intensity， openness of MPTP， the contents of CK， LDH and MDA were significantly decreased in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of MMP and ATP were all increased significantly （P＜0.01）； the contents of CK-MB， LDH and MDA in serum were all decreased significantly in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of SOD， complex Ⅰ， complex Ⅳ and ATP （except for positive control group） were increased significantly （P＜ 0.05 or P＜0.01）. CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury， promote endogenous energy production and improve mitochondrial function after myocardial ischemia.

Objective To optimize the spray drying process of Banlangen(Isatidis Radix)formula granules based on quality by design(QbD)concept.Methods Using powder yield and the contents of uridine,adenosine,guanosine,and(R,S)-goitron as the critical quality attributes(CQAs),Plackett-Burman design was used to screen out critical process parameters(CPPs)for inlet temperature,spray pressure,liquid temperature,pump speed,and liquid relative density.The central-composite design(CCD)test was used to optimize the CPPs,which were screened.Based on the quadratic polynomial regression model,the design space of spray drying process of Banlangen(Isatidis Radix)formula granules was established,and further validated by experiments.Results Plackett-burman test results show that liquid relative density and inlet velocity are the key parameters for the study.The variance analysis results of CCD test showed that the constructed model in a good prediction ability,since the P-values of model was less than 0.01 and P-values of items lack of fit was more than 0.05.The optimized design space of CPPs was the liquid relative density 1.05-1.08,and pump speed 30%-40%.Conclusion Based on the QbD concept,the design space for the spray drying process of Banlangen(Isatidis Radix)formula granules can improve the stability of its process and help ensure the consistency of product quality.

Objective:To explore the predictive value of a regression model based on diffusion kurtosis imaging (DKI) parameters for prediction of the recurrence risk in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER-2)-negative early invasive breast cancer.Methods:A retrospective cross-sectional study was designed. The clinicopathological (age, histological grade, Ki-67 level, etc.) and imaging data of 50 patients (50 lesions) with ER-positive, HER-2 negative early invasive breast cancer who underwent treatment at Wuxi People′s Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients were female, aged 29 to 81 years, and underwent pre-operation conventional MRI and DKI examinations. The volume of breast fibroglandular tissue (FGT), background parenchymal enhancement (BPE), and internal enhancement features were recorded; the peak enhancement (PH), peak enhancement rate, time to peak, mean kurtosis (MK), and mean diffusivity (MD) were calculated. Based on the 21-gene recurrence risk scores, patients were divided into low recurrence risk group and medium-high recurrence risk group. Independent sample t test, Mann-Whitney U test, χ2 test were used to compare the differences of various indicators between the two groups. Two logistic models were constructed with age, PH, MD, and MK as independent variables (Pre1), and with Ki-67, age, PH, MD, and MK as independent variables (Pre2), respectively. The efficacy of the models in predicting low recurrence risk in patients was assessed using receiver operating characteristic curve and area under the curve (AUC). Results:There were 25 cases in the low recurrence risk group and 25 cases in the medium-high recurrence risk group. The differences in age, FGT, PH, MD, MK, and Ki-67 between the low recurrence risk group and the medium-high recurrence risk group were statistically significant (all P<0.05), while other indexes showed no statistically significant differences (all P>0.05). The AUC of Pre1 in predicting low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.87, with a sensitivity of 0.76 and specificity of 0.88. The AUC of Pre2 for predicting the low recurrence risk of ER-positive, HER-2 negative early invasive breast cancer was 0.92, with a sensitivity of 0.84, and specificity of 0.92. Conclusions:A multi-parameter model based on DKI can effectively predict the recurrence risk of ER-positive and HER-2 negative breast cancer. The model with combination of Ki-67 can further improve the predictive efficacy, and help effectively identify patients at low recurrence risk.

Objective To investigate the expression and prognostic value of spindle and kinetochore-associated complex subunit 2(SKA2)in cervical cancer tissues,as well as its impact on the proliferation,migration and invasion of cervical cancer cells.Methods The expression of SKA2 in cervical cancer tissues was analyzed by bioinformatics database and immunohistochemical SP method,and the relationship between SKA2 expression level and clinicopathological features of cervical cancer patients and its prognostic value was analyzed.The mRNA expression of SKA2 in human normal cervical cells(HcerEpic)and cervical cancer cells(HeLa,SiHa,CaSki,C-33A)was detected by RT-qPCR.Cervical cancer cells SiHa with higher SKA2 expression level was selected for further study.SiHa cell model with down-regulated SKA2 expression was constructed,and its knockdown effect was verified.Cell proliferation capacity was detected by CCK-8 method,cell migration capacity was detected by cell scratch wound healing assay,and cell migration and invasion capacity was detected by Transwell assay.Results Compared with normal cervical tissues and cells,the expression levels of SKA2 mRNA and protein were higher in cervical cancer tissues and cells,and the differences were statistically significant(P<0.05).High SKA2 expression was associated with FIGO staging in patients with cervical cancer.Furthermore,SKA2 knockdown could inhibit the proliferation,migration and invasion of SiHa cells in cervical cancer(P<0.05).Conclusion SKA2 is up-regulated in cervical cancer tissues and cells,and can promote the proliferation,migration and invasion of cervical cancer cells.The expression level of SKA2 is associated with the progression of cervical cancer,and the prognosis of cervical cancer patients with high SKA2 expression is worse.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:To explore expression of VSIG4 in clear cell renal cell carcinoma(ccRCC)and its correlation with immune cells infiltration and prognosis.Methods:RNA-seq data of ccRCC and corresponding clinical data of patients were downloaded from The Cancer Genome Atlas(TCGA)database.Wilcoxon rank-sum test was used to analyze VSIG4 mRNA expression in ccRCC and normal renal tissues.Correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier method was used to analyze the correlation between VSIG4 expression and progno-sis of patients.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.Correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line 293T,and human renal carcinoma cell line ACHN,A498,786-O and OS-RC-2.Results:Expression level of VSIG4 in ccRCC was significantly higher than that in normal tissues(P<0.05).VSIG4 expression was significantly correlated with the stages of distant metastasis and lymph node metastasis(P<0.05).Overall survival rate of patients with high VSIG4 expression was significantly lower than that of patients with low expression(P<0.05).GSEA enrichment analysis showed that VSIG4 was mainly enriched in apoptosis,chemokine signaling pathway,cell adhesion molecules and other signaling path-ways.VSIG4 expression was negatively correlated with M1 macrophages(r<0,P<0.05),while positively correlated with M2 macro-phages(r>0,P<0.05).Western blotting results showed that expression of VSIG4 in renal cell carcinoma cells was higher than that in normal renal cells.Conclusion:VSIG4 is highly expressed in ccRCC,and is negatively associated with prognosis,which may become a prognostic biomarker for ccRCC patients.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Objective:The purpose of this study is to test and assess the model of modeling data of TaiChi accelerator in the Raystation Treatment Planning System(RayStation system)according to the test method and item of TG119 report of American Association Physicians Medicine(AAPM).Methods:The intensity-modulated radiation therapy(IMRT)and volumetric-modulated arc therapy(VMAT)plans of the test cases of different clinical situations,which included the simulated multi target region,prostate target region,head and neck target region,easy type C-shape target region plan and difficult type C-shape target region plan,were designed according to the AAPM TG119 report in the treatment planning system.The deviations of the doses of point and area of the two kinds of plans were measured,and the measured results were compared and analyzed with the recommended standards of AAPM TG119 report.The IBA CC13 ionization chamber and the ArcCHECK matrix ionization chamber were used respectively to verify the point dose and area dose,and the assessment standard was γ passing rate under 3%3mm.The confidence interval was adopted to judge the consistency between the measured dose and the calculated dose.Results:The accuracies of plan dose target,point dose deviation and area dose distribution of tested cases could meet the requirement of the TGl19 report.The deviations of mean doses for the high-dose points of IMRT plan and VMAT plan of tested cases were respectively(0.39±1.02)%and(1.27±0.64)%,and the confidence intervals of them were respectively 2.39%and 2.52%.The average dose deviations of low doses of organ at risk(OAR)of IMRT plan and VMAT plan were respectively(0.53±1.73)%and(0.88±1.11)%,and the confidence intervals were respectively 3.92%and 3.06%.The average γ passing rate under 3%/3mm of IMRT plan and VMAT plan were respectively(99.52±0.366)%and(99.86±0.136)%,and the confidence intervals of them were respectively 1.196%and 0.406%.Conclusion:The TaiChi accelerator performance and the accuracy of Raystation system 6MV FFF model fitting can meet the standard of TG119 report,and the subsequent standards of the quality control of equipment and patients were established according to these tested results,which would provide reference for the improvement of the performance of subsequent accelerator.

Objective To analyze the prevalence,disease burden,and trends of diabetes in China from 1999 to 2019,providing reference for diabetes prevention and control as well as health resource allocation to alleviate the disease burden.Methods Data on the disease burden of diabetes in China from 1999 to 2019 were collected from the Global Burden of Disease(GBD)2019 database.Indicators such as incidence rate,prevalence rate,mortality rate,disability-adjusted life years(DALYs),years of life lost due to premature mortality(YLLs)and years lived with disability(YLDs)were used to analyze the diabetes burden in China by gender,age and year.The estimated annual percentage change(EAPC)was used to measure the temporal trend of standardized rates over a specified period,and the rank sum test was used to assess the gender differences in disease burden.Results In 2019,3.78×106 cases of diabetes and 1.73×105 deaths were reported in China.Compared with 1999,the standardized rates of incidence and prevalence increased by 5.80%and 17.12%,respectively,while the standardized mortality rate decreased by 2.82%.Compared with 1999,the standardized rates of DALYs and YLDs increased by 2.86%and 16.06%,respectively,while the standardized YLL rate decreased by 14.39%.The EAPC for diabetes incidence,prevalence,YLDs,and DALYs in the 20-40 age group all exceed 0,indicating an annually upward trend in disease burden of diabetes.Additionally,the disease burden in males was significantly higher than that in females(P＜0.05),and the gap is continuously widening.Conclusions The disease burden of diabetes in China is severe,particularly in term of life loss due to disability.The population with diabetes onset is becoming increasingly younger.Males constitute a high-risk population for diabetes-related morbidity and mortality.Diabetes prevention and control efforts should continue to enhance behavioral interventions,appropriately tilt health resource allocation towards high-risk population,and focus on improving the rehabilitation capabilities and promoting rehabilitation technology at grass-roots unit.