Diabetic nephropathy (DN), as one of the most common complications of diabetes, is a primary cause of end-stage renal disease. The pathogenesis of DN encompasses processes such as chronic inflammation, recruitment and activation of immune cells, tubular and glomerular injury, and renal fibrosis. These processes are highly correlated with the activation of the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome and the resulting pyroptosis it mediates. Previous studies have shown that the release of pro-inflammatory cytokines, leakage of damage-associated molecular patterns (DAMPs), recruitment and activation of immune cells can be reduced by regulating the NLRP3 inflammasome and its mediated pyroptosis, thereby slowing the diffusion of inflammatory responses in adjacentcells, fibrosis, and tissue remodeling processes. Ultimately, these process can improve renal injury and dysfunction caused by diabetic nephropathy. This article summarizes the molecular regulatory mechanisms of the NLRP3 inflammasome and its mediated pyroptosis at different pathological stages of DN, proposes potential targets for regulating their activation, aiming to provide a new direction for personalized treatment of DN.

OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Objective: To explore the bidirectional associations among body mass index Z scores (BMI Z scores) and weight stigma with depressive symptoms in adolescents, thereby providing evidence for targeted intervention strategies. Methods: A stratified cluster random sampling method was employed to select 18 301 adolescents aged 12-18 years from all 12 prefectures (103 counties) in the Inner Mongolia Autonomous Region, and two waves of longitudinal surveys were conducted in September 2023 (T1) and September 2024 (T2) among the adolescents. Weight stigma was assessed by using a self developed questionnaire, depressive symptom was measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and BMI Z scores were calculated according to the World Health Organization standards. Pearson correlation analysis was used to examine associations among variables, and cross lagged panel models were constructed to investigate the dynamic bidirectional relationships among the three variables. Results: Adolescents BMI Z scores and weight stigma with depressive symptoms all exhibited autoregressive stability across the two time points (autoregressive paths, all P <0.01). Cross lagged model comparisons indicated that the bidirectional path model achieved the best fit ( χ 2=12.65, RMSEA =0.017, CFI =1.000; △ χ 2=193.39, P <0.01), supporting dynamic bidirectional associations among the three variables. After adjusting for gender, age, subjective social status and only child status, T1 BMI Z scores among adolescents positively predicted T2 weight stigma ( β =0.061), and T1 weight stigma positively predicted T2 depressive symptoms ( β =0.608); in the reverse direction, T1 depressive symptoms predicted T2 weight stigma ( β =0.003), and T1 weight stigma predicted T2 BMI Z scores ( β =0.081) (all P <0.01). Conclusions There is a bidirectional cross lagged relationship among adolescents BMI Z scores and weight stigma with depressive symptoms, suggesting that weight stigma may serve as a key psychological variable linking obesity and depressive symptoms. Greater attention should be paid to the potential threat of weight stigma to adolescents mental health, with intervention strategies expanded from a solely physiological focus to encompass psychosocial dimensions.

The gradient field, one of the core magnetic fields in magnetic resonance imaging (MRI) systems, is generated by gradient coils and plays a critical role in spatial encoding and the generation of echo signals. The uniformity or linearity of the gradient field directly impacts the quality and distortion level of MRI images. However, traditional point measurement methods lack accuracy in assessing the linearity of gradient fields, making it difficult to provide effective parameters for image distortion correction. This paper introduced a spherical measurement-based method that involved measuring the magnetic field distribution on a sphere, followed by detailed magnetic field calculations and linearity analysis. This study, applied to assess the nonlinearity of asymmetric head gradient coils, demonstrated more comprehensive and precise results compared to point measurement methods. This advancement not only strengthens the scientific basis for the design of gradient coils but also provides more reliable parameters and methods for the accurate correction of MRI image distortions.
Magnetic Resonance Imaging/instrumentation* ; Humans ; Image Processing, Computer-Assisted/methods* ; Nonlinear Dynamics ; Magnetic Fields ; Algorithms ; Phantoms, Imaging

Lung cancer is still one of the most common malignant tumors in the world. With the increase of its incidence and the development of medical technology, the overall survival of lung cancer patients has significantly extended compared to before. The incidence of brain and meningeal metastases from lung cancer has also been rising year by year, but patients with brain and meningeal metastases from lung cancer have a poor prognosis and a very high mortality rate, and the diagnosis is mainly based on computed tomography (CT), magnetic resonance imaging (MRI) and other imaging examinations. However, the imaging features are diverse and the specificity is low, which makes it easy to be misdiagnosed and missed. Therefore, accurately identifying brain and meningeal metastases and timely targeted treatment is crucial for improving patient prognosis. This paper analyzed the diagnosis and treatment of a case of lung cancer with no obvious recurrence and metastasis in nearly 7-year long-term follow-up after radical lung cancer surgery, but the patient with abnormal behavior, impaired consciousness and epilepsy in the past 5 months, and multiple punctate calcifications in the brain found by head CT and MRI. This paper consider that the patient's mental and behavioral symptoms were caused by brain and meningeal metastasis of lung cancer after excluding infectious disease and ineffective treatment of autoimmune encephalitis, and further pathological biopsy and genetic detection confirmed the diagnosis of metastatic lung adenocarcinoma with epidermal growth factor receptor (EGFR) L858R gene mutation, and the patient's symptoms were significantly improved after targeted therapy by Osimertinib. This paper also searched the relevant literatures of brain calcifications in databases such as China National Knowledge Infrastructure (CNKI), Wanfang, UpToDate, PubMed, etc., and found that intracerebral calcifications exist in a variety of diseases, including infectious, genetic and neurodegenerative diseases, vascular diseases, metabolic diseases and tumors. However, brain calcification in brain and meningeal metastases are often underestimated, and the consequent risk is misdiagnosis and delayed treatment. Therefore, brain and meningeal metastases manifested as brain calcification should not be ignored in patients with a history of previous tumors.
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Humans ; Lung Neoplasms/pathology* ; Brain Neoplasms/diagnostic imaging* ; Meningeal Neoplasms/diagnostic imaging* ; Calcinosis/diagnostic imaging* ; Male ; Middle Aged ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Objective:To investigate the application value of antegrade splenic superior region dissection first in laparoscopic total gastrectomy of obesity gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 obesity patients with gastric cancer who underwent laparoscopic total gastrectomy in Renji Hospital of Shanghai Jiaotong University School of Medicine from July 2018 to October 2023 were collected. There were 16 males and 5 females, aged (58±13)years. All 21 patients underwent laparoscopic total gastrec-tomy with antegrade splenic superior region dissection first. Observation indicators: operation time, volume of intraoperative blood loss, laparotomy conversion, intraoperative splenic hemorrhage or gastric hemorrhage, lymph node dissection, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay, postoperative complication. Measure-ment data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:All 21 patients underwent laparoscopic total gastrectomy success-fully, with the operation time of (283±47)minutes, time for splenogastric ligament and vascular manage-ment of (34±12)minutes, volume of intraoperative blood loss of (143±86)mL, and no laparotomy conversion. There was no intraoperative splenic hemorrhage or gastric haemorrhage. The total number of lymph node dissected in 21 patients was 375, with the number of lymph node dissected as (21±9)per case. Time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay in 21 patients were (3.1±0.7)days, (4.0±0.8)days and (10.1±3.0)days, respectively. There were 2 patients with postoperative complications, including 1 case of incision infection and 1 case of lung infection. The 2 patients with postoperative com-plications were recovered and discharged after conservative treatment. There was no death during the postoperative 30 days.Conclusion:The application of antegrade splenic superior region dissec-tion first in laparoscopic total gastrectomy is safe and feasible, which can reduce surgical difficulty.

Objective:To explore the effect of multidisciplinary management combined with 60-second high-risk diabetic foot screening in diabetic foot.Methods:From January to December 2022, 138 patients with diabetic foot were selected from Xinxiang Central Hospital by convenience sampling. The patients were randomly divided into a control group and an observation group, with 69 cases in each group. Control group implemented routine follow-up management of diabetic foot, and observation group carried out multidisciplinary management combined with 60-second high-risk diabetic foot screening on the basis of control group, and the intervention lasted for six months. The progress of Wagner grading of diabetic foot and foot self-care were compared between the two groups.Results:After intervention, the number of Wagner grading progression patients in observation group and control group was four cases (5.80%) and 10 cases (14.49%), respectively. The number of progression patients in observation group was less than that in control group, and the difference was statistically significant (χ 2=4.161, P=0.041). The total score and dimension scores of diabetic foot self-management in the two groups after the intervention were higher than those before the intervention, but only the scores of observation group before and after the intervention were statistically significant ( P<0.05). After intervention, the total score and dimension scores of diabetic foot self-management in observation group were higher than those in control group, with a statistically significant difference ( P<0.05) . Conclusions:Multidisciplinary management combined with 60-second high-risk diabetic foot screening can effectively delay the progress of diabetic foot and improve patients' foot self-care.

Through the effective application of Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices(EP),to continuously improve the corresponding management tools to ensure the safety and effectiveness of medical device in the quality management system,risk management system,evaluation of safety and effectiveness for the supervision departments and manufacturers.The current status of the application of EP and the application issues are analyzed in the study.Take artificial joint products for example,the idea of using EP in quality management system,risk management system and evaluation of safety and effectiveness is investigated,and several thoughts are proposed.Supervision departments should strengthen the unified understanding of EP,develop requirements according to the classification of medical device,and refine specific execution requirements.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.