OBJECTIVES: To investigate the regulatory effect of LINC00837/miR-671-5p/SERPINE2 functional axis on pathological processes of fibroblast-like synovial cells (FLS) in rheumatoid arthritis (RA). METHODS: RA-FLS were transfected with a LINC00837 overexpression plasmid (pcDNA3.1-LINC00837), a LINC00837 interference plasmid (siRNA-LINC00837), or their respective negative control plasmids (pcDNA3.1-NC and siRNA-NC). Dual luciferase was used to verify the targeting relationship between LINC00837 and miR-671-5p and between miR-671-5p and SERPINE2. RT-qPCR was used to detect the expression levels of LINC00837, miR-671-5p and SERPINE2 in normal FLS or the transfected cells, whose proliferation and migration abilities were assessed using Edu assay and scratch healing assay and by detecting the expression levels of Ki-67, PCNA, E-cadherin and N-cadherin with Western blotting. The changes in cellular secretion of the inflammatory cytokines (TNF‑α, IL-17, IL-4 and IL-10) were examined using ELISA. RESULTS: Dual luciferase reporter gene assay showed that LINC00837 was capable of binding to the 3'-UTR of miR-671-5p, and the latter bound to the 3-UTR of SERPINE2 at specific binding sites between them. Compared with normal FLS, RA-FLS showed significantly increased expressions of LINC00837 and SERPINE2, lowered miR-671-5p expression and enhanced proliferation and migration abilities with increased expressions of pro-inflammatory cytokines and reduced expressions of anti-inflammatory cytokines. Transfection of RA-FLS with pcDNA-LINC00837 further enhanced cell proliferation and migration and the changes in the inflammatory cytokines, while transfection with si-LINC00837 produced the opposite changes. CONCLUSIONS RA-FLS have a LINC00837/miR-671-5p/SERPINE2 functional axis, which regulates cell proliferation, migration and secretion of inflammatory factors, and interventions targeting LINC00837 may provide a potential strategy to regulate the pathological processes in RA-FLS.
Arthritis, Rheumatoid/metabolism* ; MicroRNAs/metabolism* ; Humans ; Cell Proliferation ; Cell Movement ; Synovial Membrane/pathology* ; RNA, Long Noncoding/genetics* ; Fibroblasts/metabolism* ; Synoviocytes/metabolism* ; Cells, Cultured ; Transfection

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 explore the pathogenesis,clinical features,treatment strategies,and prognosis of pediatric lymphoepithelioma-like carcinoma(LELC).Methods:A retrospective analysis was conducted on the clinical data of patients with LELC aged<18 years,treated at Sun Yat-sen University Cancer Center from March 2008 to June 2023.Results:A total of 19 children and adolescents were included in the analys-is,comprising 10 males(52.6%)and 9 females(47.4%),with a median age of 12.9(4.3-17.0)years.Fourteen patients(73.7%)lived in Guangdong province,with the remainder scattered across other regions.Primary LELC sites were the mediastinum(11 cases,57.9%),parot-id glands(4 cases,21%),neck(1 case,5.3%),lungs(1 case,5.3%),salivary glands(1 case,5.3%),and submandibular glands(1 case,5.3%).Among these,15 patients(78.9%)had at least one distant metastasis at initial diagnosis,with common metastasis sites being cervical lymph nodes.Multivariate Cox regression analysis identified tumor volume≥801 cm3 as an independent adverse prognostic factor of poor overall survival(OS)(P<0.01).The 2-year OS and progression-free survival(PFS)rates were 84.2%and 57.9%,respectively.The 2-year OS for pa-tients who underwent surgery,chemotherapy,and radiotherapy was 100%,compared with 25%for those who received only partial treat-ment(P=0.007).The 2-year PFS rate was significantly higher in patients receiving first-line combination therapy with programmed death-1(PD-1)antibodies(100%)compared with those not treated with PD-1 antibodies(38.5%)(P=0.020).For patients with tumor volume≥801 cm3,the 2-year OS was 40.0%,whereas for those with a tumor volume<801 cm3,the 2-year OS was 100%(P<0.001).The 2-year OS for pa-tients who underwent radiotherapy was 100%,while it was 0 for those who did not receive radiotherapy(P<0.001).Conclusions:Pediatric LELC exhibits a relatively favorable prognosis with multidisciplinary treatment,including surgery,chemotherapy,and radiotherapy.The com-bined use of PD-1 antibodies at the time of initial diagnosis could offer potential benefits and warrants further exploration.

Objective:To compare the differences of three-dimensional computed tomography(3DCT),four-dimensional computed tomography(4DCT),and multi-parametric magnetic resonance(MR)sequences of the radiotherapy for liver cancer in delineation for target area,and analyze which MR sequence was more accurate in assisting CT image to delineate the target area,and design respectively reverse intensity modulated radiotherapy plan,and compare the dosimetric parameters of the target areas of receiving radiotherapy and normal liver tissue.Methods:This retrospective study was conducted to analyze radiotherapy data from case data of 18 patients with hepatocellular carcinoma(HCC)who admitted to the First Affiliated Hospital of Bengbu Medical University between August 2023 and June 2024.These data included 10 respiratory phases in 3DCT and 4DCT,and free-breathing sequence(MR-FB),diaphragm navigation sequence(MR-NAVI),and breath-hold(MR-BH)sequence of multi-parametric MRI,and the gross tumor volumes(GTVs)of them were delineated,which were respectively 5 modal images and liver contours included GTV3D,GTV4D,GTVMR-FB,GTVMR-NAVI,and GTVMR-BH.Pinnacle3 9.8 treatment plan system(TPS)was applied to conduct registration and fusion for image by using mutual information method.The 3DCT(GTV3D)was used as reference image to compare the volume of target area,and the displacement of mass center with other 4 kinds of images.The volume difference(VD),overlap ratio(OR),Dice similarity coefficient(DSC),and Jaccard index(JAC)were used to assess the differences among different target area.The indicators of plan evaluation included conformity index(CI),homogeneity index(HI),GTV doses(D2%,D98%,Dmean),and the exposure dose of normal tissue of liver.Results:In images of five modalities,the GTV median volumes were respectively 28.83,33.10,26.75,25.05,and 22.65 cm3.In images of five modalities,the median volume of liver were respectively 1293.46,1483.09,1213.81,1195.69,and 1141.02 cm3.Compared with other 3 target areas,the displacement of GTVMR-BH was the smallest on head-foot direction,with statistically significant differences among them(Z=-2.305,-2.307,-2.134,P<0.05).The OR,DSC,and JAC values of GTV4D were significantly better than these of GTVMR-FB,GTVMR-NAVI,and GTVMR-BH(ZOR=-2.911,-3.006,-3.195,ZDSC=-2.726,-2.215,-2.556,ZJAC=-2.556,-2.704,-2.953,P<0.05).The VD value of GTVMR-FB was better than that of GTV4D,GTVMR-NAVI,and GTVMR-BH,with statistically significant(Z=-2.675,-2.817,-2.580,P<0.05).Additionally,the OR,DSC,and JAC values of GTVMR-FB and GTVMR-NAVI were better than those of GTVMR-BH,with statistically significant(ZOR=-2.859,-2.817,ZDSC=-2.184,-2.783,ZJAC=-2.385,-2.783,P<0.05).All five plans met clinical dose requirements.Friedman test showed there was no statistically significant differences in dosimetric parameters of target area among different plans(P>0.05).However,compared to the PTV3D plan,the PTVMR-FB,PTVMR-NAVI,and PTVMR-BH plans resulted in lower levels in mean dose(Dmean)of liver and volume parameters(V5,V10,V20,V30)of various doses,with statistically significant differences(Dmean:Z=-2.433,-2.307,-2.807,ZV5=-2.512,-2.433,-2.652,ZV10=-2.433,-2.536,-2.968,ZV20=-2.536,-2.652,-2.807,ZV30=-2.611,-2.652,-2.968,P<0.05).Conclusion:In actually clinical application,MR-NAVI and 4DCT also can be adopted to assist 3DCT to delineate target area besides MR-FB sequence that is conventionally used in MR location,thus can enhance precision of delineation,and optimize radiotherapy plan,and decrease exposure dose of normal liver tissue.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for low-dose chest CT images of infants with congenital heart disease.Methods Totally 262 infants with congenital heart disease who would undergo chest CT scanning were prospectively enrolled and randomly divided into low-dose group(n=142)and conventional dose group(n=120).Chest CT scanning with tube voltage of 80 kVp and tube current of 10 mAs was performed in low-dose group,and hybrid iterative reconstruction(HIR,group A)and AIIR(group B)were used to reconstruct images,respectively.In conventional dose group,chest CT scanning with tube voltage of 80 kVp and tube current of 100 mAs was performed,and HIR was used to reconstruct images(group C).Then subjective and objective evaluation on image quality were performed,the results were compared among 3 groups,and the value of AIIR was analyzed.Results Significant differences of image quality and clarity of displaying structures were found among 3 groups(all P＜0.001).Among them,except for the clarity of interlobar fissure,no significant difference of subjective scores was found between low-dose AIIR images and conventional dose HIR images(all corrected P＞0.05),while subjective scores of low-dose HIR images were all lower than those of low-dose AIIR images and conventional dose HIR images(all corrected P＜0.05).Significant differences of standard deviation(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were found among 3 groups(all P＜0.001)and between each 2 groups(all corrected P＜0.05).The effective dose of low-dose group and conventional dose group was 0.09(0.08,0.10)and 0.85(0.75,1.03)mSv,respectively,and the former was lower than the latter(Z=-13.942,P＜0.001).Conclusion Using AIIR could obtain low-dose chest CT images of infants with quality comparable to conventional chest CT images.

Objective:To explore the clinical efficacy of targeted epidural space block combined with acupotomy in the treatment for lumbar disc herniation(LDH)under the monitor of X-ray image,and to analyze the safety of its operation.Methods:A total of 60 LDH patients who admitted to Department of Pain,Jiangyin Affiliated Hospital of Nanjing University of Chinese Medicine from January 2022 to September 2023 were selected,and they were randomly divided into observation group and control group as random number table,with 30 cases in each group.The observation group adopted targeted epidural space block combined with acupotomy under monitor with X-ray for anterior epidural space,while the control group adopted conventionally epidural block,all of which were treated only once.The Visual Analogue Scale(VAS)scores and Oswestry Disability Index(ODI)scores of two groups before treatment and at the 3rd day,7th day and 30th day after treatment were compared.At the 30th day after treatment,the curative effects of two groups were evaluated according to ODI scores,at the same time,the safe distance between puncture and acupotomy in patients of observation group was analyzed.Results:The effective rates of the treatment of observation group and control group were respectively 96.67%and 70%,and the difference of that between the two groups was statistically significant(x2=7.680,P<0.05).The VAS scores of the two groups at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the observation group(2.30±0.87),(1.53±0.86)and(1.47±0.81)were lower than the control group(4.43±0.89),(2.23±0.89)and(4.27±0.82),the difference was statistically significant(t=9.374,3.098,13.306,P<0.05).The ODI scores of the two groups were at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the differences of them between two groups were statistically significant(t=7.112,10.690,10.151,P<0.05).In 30 patients of observation group,the gap between the dural sac and the inner edge of facet joint on the affected side was larger than 4.0mm in 25 cases,and all of them can safely conduct puncture with targeting.Conclusion:The targeted epidural space block combined with acupotomy by adopting monitor with X-ray image can effectively improve the symptom of pain,and activities of daily life of LDH patients,which treatment is safe and effective.

Objective:To evaluate the diagnostic value of targeted next-generation sequencing (tNGS) of throat swab samples for detecting community-acquired respiratory viruses (CARV) in patients with hematological diseases.Methods:Clinical and laboratory data from 64 episodes involving patients with hematological diseases and suspected infections—who underwent both pharyngeal swab tNGS and CARV polymerase chain reaction (PCR) testing concurrently—were retrospectively analyzed. The cases were drawn from the Department of Hematology, Peking University People’s Hospital, between September 2023 and April 2024. Concordance between tNGS and CARV PCR results, as well as the diagnostic performance of tNGS in detecting CARV, were evaluated.Results:Among the 64 episodes, 29 were clinically diagnosed with respiratory tract infections, including one case of cytomegalovirus pneumonia and 28 CARV-positive cases. The remaining 35 episodes involved patients with fever or respiratory symptoms attributed to other causes, including 14 with extrapulmonary infections and 21 with noninfectious etiologies. The median follow-up duration was 215.5 days (range: 7-271 days). PCR detected 24 strains of seven CARV types, whereas tNGS detected 25 strains of eight CARV types. Using PCR results as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of tNGS were 85.0%, 88.6%, 77.3%, 92.9%, and 87.5%, respectively. The two methods showed good concordance (Kappa=0.717, P<0.001) . Conclusion:Pharyngeal swab tNGS may serve as a viable alternative to PCR for diagnosing CARV infections in patients with hematological diseases.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

Tumor immunotherapy has attracted worldwide attention in cancer treatment because of its obvious advantages such as strong specificity and long curative effect.It is found that activation of STING signaling pathway in cells is one of directions to effec-tively realize tumor immunotherapy.However,due to low response rate of related drugs,difficult degradation,certain toxic and side effects,its clinical application has been seriously hindered.Nano-drug delivery system can achieve targeted drug delivery,improve drug stability,delivery rate,osmotic effect and long-term retention effect,reduce drug side effects,and show significant advantages in tumor immunotherapy.In this paper,research progress of nano-drug delivery system activating STING pathway in tumor immunother-apy in recent years is reviewed,and many nano-drug delivery systems that can activate STING signal pathway and their application ex-amples after loading drugs are listed,including nucleotide-based drug delivery system,non-nucleotide-based drug delivery system and metal-based drug delivery system,providing reference for application of nano-drugs in tumor immunotherapy.

Objective:To investigate the application effects of electroacupuncture at Chang'an acupoint combined with stimulation of Huatuo Jiaji acupoint on non-specific low back pain. Methods:A retrospective analysis was conducted on the clinical data of 200 patients with non-specific low back pain admitted to the Hanzhong Hospital of Traditional Chinese Medicine from October 2021 to October 2022. The patients were divided into two groups based on different treatment methods: a control group and an observation group, with 100 patients in each group. The control group received conventional electroacupuncture treatment, while the observation group received electroacupuncture at the Chang'an acupoint and stimulation of Huatuo Jiaji acupoint. Both groups were treated for three treatment courses. Clinical efficacy was compared between the two groups. Results:The total response rate in the observation group was 97% (97/100), which was significantly higher than the 84% (84/100) in the control group ( χ2 = 9.83, P = 0.002). After treatment, both groups showed an increase in the Japanese Orthopaedic Association score for low back pain (both P<0.05) compared with before treatment. The Japanese Orthopaedic Association score in the observation group was significantly higher than that in the control group [(23.54 ± 1.81) vs. (20.75 ± 1.57), t = 11.64, P<0.001]. Conclusions:Electroacupuncture at the Chang'an acupoint combined with stimulation of the Huatuo Jiaji acupoints is effective in relieving pain, improving lumbar function, and enhancing clinical outcomes in patients with non-specific low back pain.