BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Objective:To explore the value of Alberta stroke program early CT Score (ASPECTS) regional net water intake (NWU) based on plain CT in evaluating the neurological outcome of patients with acute large vessel occlusive stroke (ALVOS) after mechanical thrombectomy.Methods:The study was a prospective cross-sectional study. The clinical and imaging data of patients with ALVOS who underwent mechanical thrombectomy in the 904 Hospital of the PLA Joint Service Support Force from June 2022 to June 2024 were prospectively collected. Clinical data analysis included age, gender distribution, National Institutes of Health Stroke Scale (NIHSS) score and Glasgow Coma Scale (GCS) score at admission. All patients underwent plain CT and CT angiography (CTA). Automated processing software quantified ischemic brain edema by calculating ASPECTS and measuring the ASPECTS regional NWU rate (CT-ASPECTS-NWU) based on plain CT. Cerebral collateral circulation was assessed using CTA images. According to the modified Rankin Scale score of patients with mechanical thrombectomy 90 days after the telephone follow-up, 0-2 points were defined as good neurological outcome, and 3-6 points were defined as poor neurological outcome. Independent samples t test, Mann-Whitney U test and χ2 test were used to analyze the differences of clinical and imaging indicators between patients with good and poor neurological outcome, indicators with statistically significant differences were included in multivariate logistic regression analysis to screen out the independent influencing factors that predicted the neurological outcome of patients with ALVOS after mechanical thrombectomys. The efficacy of related indicators to predict neurological outcomes after mechanical thrombectomy in patients with ALVOS was evaluated using receiver operating characteristic (ROC) curve analysis, with the area under the curve (AUC) calculated. Results:A total of 122 patients with ALVOS were included, including 101 patients with good neurological outcome and 21 patients with poor neurological outcome after mechanical thrombectomy. There were statistically significant differences in preoperative GCS score, collateral circulation status, NIHSS score at admission, preoperative ASPECTS and CT-ASPECTS-NWU between patients with good neurological outcome and patients with poor neurological outcome ( P<0.05). Multivariate logistic regression analysis showed that the status of collateral circulation ( OR=3.450, 95% CI 1.158-10.277, P=0.026), preoperative ASPECTS ( OR=0.510, 95% CI 0.274-0.952, P=0.034) and CT-ASPECTS-NWU ( OR=2.131, 95% CI 1.301-3.493, P=0.003) were independent predictors of neurological outcome in patients with ALVOS after mechanical thrombectomy. ROC curve analysis showed that CT-ASPECTS-NWU had the highest predictive value, with an AUC of 0.881, a sensitivity of 85.7%, a specificity of 85.1%, and an optimal cutoff value of 7.55. Conclusion:CT-ASPECTS-NWU demonstrates high diagnostic value in evaluating the neurological outcome of patients with ALVOS after mechanical thrombectomy, and can provide an objective imaging biomarker to guide clinical decision-making.

Objective To observe and analyze the clinical efficacy and safety of carvedilol combined with dual-wavelength pulsed dye laser in the treatment of rosacea.Methods A retrospective analysis was per-formed on 50 patients with rosacea mainly characterized by flushing,erythema,and telangiectasia who were treated with dual-wavelength pulsed dye laser in the Department of Dermatology of this hospital from October 2023 to October 2024.They were divided into the observation group and the control group according to differ-ent treatment methods,with 25 cases in each group.The control group received dual-wavelength pulsed dye la-ser treatment,while the observation group received carvedilol combined with dual-wavelength pulsed dye laser treatment.The clinical erythema assessment(CEA)scale and physician global assessment(PGA)were used to evaluate the efficacy of the two groups,and the occurrence of adverse reactions was recorded.Results After treatment,the CEA scores of both groups were lower than those before treatment.The CEA score of the ob-servation group was lower than that of the control group,and the PGA score was higher than that of the con-trol group,with statistically significant differences(P<0.05).No singnifcant adverse reactions occurred in ei-ther group.Conclusion Carvedilol combined with dual-wavelength pulsed dye laser is more effective than sin-gle dual-wavelength pulsed dye laser in the treatment of rosacea,and the treatment method is safe.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.

Objective:To investigate the differential impact of ultra-high-resolution photon-counting detector CT (UHR PCD-CT) and energy-integrating detector CT (EID-CT) on image quality and calcified plaque-induced luminal stenosis in coronary CT angiography (CCTA).Methods:This retrospective analysis was conducted on patients who underwent both EID-CT and UHR PCD-CT CCTA at the Geriatric Hospital of Nanjing Medical University between January 2021 and November 2024. A total of 141 patients were included in the study, within 46 patients having scans within a 12-month interval. Image quality of all coronary artery segments was subjectively evaluated. Patients with paired scans (interval≤12 months) were included for calcified plaque analysis. Subjective visualization of calcified plaques evaluated. The blooming artifact was calculated as an objective evaluation index for assessing the calcified plaques. Additionally, the degree of coronary artery lumen stenosis resulting from calcified plaques was assessed, along with the measurement of plaque volume and the Agatston score. Changes in lumen stenosis between the two scans were also evaluated. The Wilcoxon signed-rank test was used to compare the subjective scores of coronary artery image quality and calcified plaques between the two groups, and paired-sample t-tests were used to compare the blooming artifact and lumen stenosis degree. Results:The PCD-CT image quality score was significantly higher than that of EID-CT [PCD-CT : 5 (4,5), EID-CT: 4 (4,5); Z=-21.38, P<0.001]. Compared to EID-CT, PCD-CT reduced the blooming artifact (PCD-CT: 38.88%±9.09%, EID-CT: 50.11%±11.52%; t=-12.97, P<0.001), significantly improving the subjective score for visualization of calcified plaques [PCD-CT: 5 (4,5), EID-CT: 3 (2,3); Z=-9.68, P<0.001], and the measured lumen stenosis was notably lower in PCD-CT(PCD-CT:34.88%±18.20%, EID-CT:45.31%±23.42%; t=-9.93, P<0.001). Among 129 analyzed calcified plaques, luminal stenosis was reduced on PCD-CT in 110 plaques (85.3%) and increased in 19 (14.7%), including 4 plaques that had unclear boundaries with the adjacent lumen in EID-CT CCTA images, making the stenosis difficult to assess. Conclusion:Compared to EID-CT, UHR PCD-CT for CCTA significantly improves coronary artery image quality, provides clearer visualization of calcified plaques and adjacent lumen details, and it can reduce the overestimation of coronary artery caleified plaque stenosis.

Objective To investigate the correlation between novel bone metabolism markers and the degree of aortic calcification as well as cardiovascular event risk in elderly patients treated by PD.Methods A prospective trial was conducted on 230 elderly patients receiving continuous am-bulatory PD in our department from February 2022 to February 2024.According to the occur-rence of cardiovascular events during dialysis treatment,they were divided into a cardiovascular event group(n=92)and a control group(n=138).Relevant clinical data were collected,aortic calcification was assessed using AAC scores,and serum levels of bone metabolism markers,inclu-ding osteoprotegerin,TRACP,and PINP were measured.Results The serum levels of osteoprote-gerin,TRACP and PINP were significantly higher in the cardiovascular event group than the con-trol group(P＜0.01).The cardiovascular event group had obviously severe calcification and higher AAC score than the control group(P＜0.01).The serum levels of the three bone metabolism markers were notably higher in the patients with severe calcification than those with moderate calcification,followed by mild calcification in turn(P＜0.01).Spearman correlation analysis indi-cated that the levels of the three indicators were positively correlated with the degree of aortic cal-cification in elderly PD patients(r=0.465,P=0.000;r=0.396,P=0.000;r=0.434,P=0.000).Multivariate logistic regression analysis showed that these three indicators were risk factors for cardiovascular events in elderly PD patients(P＜0.01).Conclusion The three bone metabolism markers are significantly correlated with aortic calcification severity and cardiovascular event risk in elderly PD patients.Monitoring these marker levels may be helpful for the assessment and man-agement of cardiovascular risk.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.