Objective To investigate the effects of ROCK-siRNA transfection on endothelial cell senescence and endothelial microparticles (EMPs) induced by angiotensin II (Ang II). Methods Human umbilical vein endothelial cells (HUVECs) were treated with Ang II (1.0 μmo/L) to induce cellular senescence models, followed by transfection with ROCK-siRNA. The cells were divided into four groups: control group, model group, negative transfection control group (Ang II combined with NC-siRNA), and ROCK-siRNA transfection group (Ang II combined with ROCK-siRNA). Cellular senescence was assessed by SA-β-Gal staining. EMP levels in cell supernatants and intracellular reactive oxygen species (ROS) levels were assessed using flow cytometry. The expression levels of silenced information regulator 1(SIRT1) and p53 protein in each group were analyzed by Western blotting. Results Following ROCK-siRNA transfection, the number of senescent cells induced by Ang II was significantly reduced, accompanied by decreased CD31⁺ EMP levels and suppressed intracellular ROS levels. Meanwhile, the expression levels of SIRT1 were up-regulated, while the expression levels of p53 were down-regulated. Conclusion Silencing ROCK expression suppresses EMP release, reduces ROS generation, regulates the expression of SIRT1 and p53, and ultimately attenuates Ang II-induced endothelial cell senescence.
Humans ; Angiotensin II/pharmacology* ; Cellular Senescence/genetics* ; Human Umbilical Vein Endothelial Cells/cytology* ; RNA, Small Interfering/metabolism* ; Reactive Oxygen Species/metabolism* ; Sirtuin 1/genetics* ; Transfection ; Tumor Suppressor Protein p53/genetics* ; Cell-Derived Microparticles/drug effects* ; rho-Associated Kinases/metabolism* ; Endothelial Cells/metabolism* ; Cells, Cultured

Organ damage from cancer treatment remarkably effects patients’ prognosis and quality of life. In recent years, preventive organ protection strategies, such as interdisciplinary collaboration, early prevention, precision interventions, psychological support, and the integrated application of traditional Chinese medicine, have demonstrated substantial clinical value and achieved notable progress. However, these approaches still encounter multiple challenges. Establishing multidisciplinary teams, optimizing therapeutic balance, and strengthening evidence-based research are essential for addressing the challenges related to treatment balance optimization, multidisciplinary coordination, and clinical translation of novel technologies. This review systematically summarizes recent advancements in preventive organ protection, analyzes existing challenges and potential solutions, and offers forward-looking recommendations. It aims to provide valuable insights for optimizing comprehensive cancer treatment strategies and improving long-term patient outcomes.

[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.

Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.

Objective:To analyze the clinical characteristics of familial hypercholesterolemia (FH) in children and provide a basis for clinical diagnosis and individualized treatment.Methods:Case series study. Clinical data of 24 children with FH, who were admitted to the Department of Endocrinology in Capital Center for Children′s Health, Capital Medical University, from January 2018 to January 2025, were analyzed. Follow-ups were performed every 3-6 months and ended in January 2025. According to the results of genetic testing, the children were divided into homozygous familial hypercholesterolemia (HoFH) group and heterozygous familial hypercholesterolemia (HeFH) group. The blood lipid levels of different subtypes, the efficacy of different treatments, and clinical outcomes were compared by Mann-Whitney U test. Results:The 24 children were from 17 families, including 14 males and 10 females, with a diagnostic age of 5.0 (3.0, 9.5) years. Genetic testing results showed that 22 cases (92%) had LDLR gene variants and 2 cases (8%) had APOB gene variants, all of which were inherited from parents. There were 5 cases (21%) of HoFH and 19 cases (79%) of HeFH, and 4 previously unreported new loci were identified. There were 6 children (25%) presented with xanthomas, including 5 cases of HoFH and 1 case of HeFH. The level of low-density lipoprotein cholesterol (LDL-C) in the HoFH group was significantly higher than that in the HeFH group ( P<0.05). Regarding treatment, 11 children received dietary control without taking medicine, 6 were treated with statins, 3 with ezetimibe, and 3 with statins combined with ezetimibe, and 1 underwent liver transplantation. None of the children receiving only dietary control achieved the target LDL-C level (<3.49 mmol/L or a reduction of >50%), and there was no statistically significant difference in LDL-C before and after dietary control ( P=0.158). After treatment with statins and (or) ezetimibe, LDL-C decreased in 12 children ( P<0.05); among them, 6 cases (all HeFH) reached the target LDL-C level. There was no statistically difference in LDL-C levels before and after treatment with atorvastatin and ezetimibe in 5 HoFH children( P>0.05). One HoFH child had LDL-C reduced to the normal range after liver transplantation. No serious adverse reactions were observed in all children during drug treatment. In the detection of vascular-related complications among 12 HeFH children, only 1 child had a slight thickening of the bilateral carotid intima-media, while no abnormalities were found in the others. Conclusions:Xanthoma is a characteristic manifestation of FH, but its incidence is relatively low in HeFH children. Family history and genetic testing are key evidences for the diagnosis of FH. Dietary control has limited efficacy in children with FH, and drug treatment should be initiated as early as possible. LDL-C levels in HoFH children are more difficult to control, if drug treatment shows poor efficacy, liver transplantation may be a better option.

Objective:To investigate the expression characteristics of plasma proteins in patients with acute diquat poisoning by proteomic technology, and to screen the targets and biomarkers related to the diagnosis, treatment and prognosis of acute diquat poisoning.Methods:This study was a retrospective case-control study. Patients with diquat poisoning admitted to Nanjing University Affiliated Drum Tower Hospital from August 2022 to December 2023 were enrolled. Healthy volunteers matched for age and gender during the same period were selected as the control group. The general clinical data and plasma samples were collected, and qualitative and quantitative analyses of plasma proteins were performed by proteomic technology based on nanoliter liquid chromatography tandem quadrupole time-of-flight mass spectrometry. Mann-Whitney U test was used to compare differences of plasma protein expression between the two groups. Results:A total of 8 diquat poisoning patients and 7 healthy individuals were included in this study, and 491 plasma proteins were identified. Compared with control group, 76 differentially expressed proteins were obtained from the poisoned group, including 35 up-regulated proteins and 41 down-regulated proteins. GO analysis showed that the differentially expressed proteins were mainly associated with oxygen transporter activity, receptor binding, and hyaluronic acid-binding endopeptidase inhibitor activity. KEGG pathway enrichment analysis revealed that differentially expressed proteins were associated with complement and coagulation cascades, neutrophil extracellular trap formation, and platelet activation. In addition, the expression of adiponectin (ADIPOQ) was not only increased in poisoned patients, but also significantly higher in non-survivors than in survivors ( P<0.01). Conclusions:Multiple plasma proteins with abnormal expression may be involved in the pathological process of acute diquat poisoning. ADIPOQ may have potential application value in the diagnosis, treatment, and prognosis of acute diquat poisoning.

Objective To establish orthotopic and ectopic pancreatic cancer models in C57BL/6N mice with normal immune function using in vivo imaging technology for visual characterization.Methods Orthotopic and ectopic pancreatic cancer models were established in Kunming mice by injecting a small volume of cell suspension containing firefly luciferase-expressing Panc02-luciferase pancreatic cancer cells into the head of the pancreas or the right axillary region.In vivo imaging technology was used to optimize the modeling method and timing in Kunming mice.Subsequently,the same method was applied to C57BL/6N mice using wild-type Panc02 pancreatic cancer cells to establish orthotopic and ectopic pancreatic cancer models with intact immune function.Key parameters,including body weight,inoculation positive rate,tumor growth time,tumor volume,and pathological characteristics across different organs,were compared be-tween the orthotopic and ectopic models in C57BL/6N mice to evaluate the applicability of these models.Results Both the small animal in vivo imaging experiments in Kunming mice and the tumor growth observation in C57BL/6N mice demonstrated that the construction periods for orthotopic and ectopic pancreatic cancer models were 20 days,with survival rates exceeding 90%.The inoculation positive rates in C57BL/6N mice were 92.3%for the orthotopic model and 78.6%for the ectopic model.On day 20 post-inoculation,the tumor volumes were(117.04±109.56)mm3 for the orthotopic model and(155.68±168.73)mm3 for the ectopic model,indicating high model success rates and consistent tumor growth.HE staining revealed pathological mitotic figures and poorly differentiated tumor tissues in both models of C57BL/6N mice,with no evidence of metastasis to other organs.Conclusions Orthotopic and ectopic pancreatic cancer models in immu-nocompetent mice were successfully developed in this study,mimicking early-stage pancreatic cancer characteristics.These models pro-vide a reliable platform for screening early diagnostic biomarkers and evaluating therapeutic interventions for pancreatic cancer.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Objective To investigate the differences of condylar position in patients with temporomandibular disorders(TMD),and to further explore the effects of condylar position displacement and malocclusion factors on TMD.Methods According to the inclusion criteria,normal occlusion subjects without TMD(group A,n=10),normal occlusion subjects with TMD(group B,n=8),malocclu-sion subjects without TMD(group C,n=9)and malocclusion subjects with TMD(group D,n=20)were collected.Condylar position measurement(CPM)and Cadiax Ⅳ were used to locate the position of condyle in RP and ICP,and the displacement and direction of condyle in three-dimensional direction from RP to ICP were measured by vernier caliper.All the data were averaged three times and an-alyzed by SPSS26.0 statistical software.Results In the sagittal direction,the condylar displacement of group A and group B,group C and group D,and group A and group D had statistical differences(P＜0.01).The displacement of the right condyle in the vertical direc-tion of group D was greater than that of group A,and the difference was statistically significant(P＜0.05).The difference among other groups was not statistically significant.There was no significant difference in the lateral displacement of condyle between the four groups.In group A and group D,the largest proportion of condyle deviation was anterior up,while in group B and group C,the largest proportion of condyle deviation was posterior up.Conclusion RP-ICP condylar sagittal displacement is common in people with TMD.The condyle displacement of RP-ICP in malocclusion patients without TMD is not significantly different from that in normal occlusion patients without TMD.Patients with TMD malocclusion are more likely to have condylar displacement in sagittal direction and vertical direction than normal occlusion without TMD.

Lung cancer is one of the most prevalent malignant tumors,which incidence and mortality rates increasing annually.Development of drug resistance is a primary factor contributing to treatment failure.Tumor-associated macrophages(TAMs),as key immune cells within tumor microenvironment(TME),play a significant role in the emergence and progression of drug resistance in tu-mors.TAMs can polarize into two distinct subtypes,M1 and M2,in response to diverse signaling stimuli.Research indicates that M2 TAMs are closely associated with poor prognoses in lung cancer,facilitating drug resistance through mechanisms such as promoting angiogenesis,enabling immune evasion,inducing stem cell-like characteristics in tumors,modulating relevant signaling pathways,and secreting cytokines.Traditional Chinese medicine(TCM)is characterized by its multi-target approach and minimal toxic side effects,it has been shown to enhance tumor sensitivity to drugs,slow malignant progression,and extend patient survival.This paper reviews the relationship between TAMs and lung cancer drug resistance while summarizing current research on TCM and their active components that regulate TAM activity to mitigate drug resistance in lung cancer,aiming to provide new insights for targeting TAMs in this context.