ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

Uveal melanoma(UM)is the most common primary intraocular malignancy in adults and arises predominantly from the choroid. Mitochondria, as essential organelles, not only fuel energy metabolism, but also orchestrate signal transduction and apoptosis. Recent studies have progressively uncovered the multifaceted roles of mitochondria in UM, including mitochondrial DNA copy-number alterations, reprogramming of mitochondria-related metabolic genes, and mitochondria-dependent autophagy. Moreover, mitochondria modulate UM progression partly through the PI3K/AKT axis. Natural compounds and small-molecule drugs that impair mitochondrial function have also shown promising activity in inducing UM cell dysfunction. These findings provide new insights into UM pathogenesis and highlight mitochondria as potential therapeutic targets.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

ObjectiveTo explore the effects of Renshentang on atherosclerosis （AS） in mice based on the role of transient receptor potential vanilloid1 （TRPV1） in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group， and 60 ApoE^-/- mice were randomized into model， positive drug （simvastatin， 0.02 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.77， 3.54， 7.08 g·kg^-1·d^-1， respectively） Renshentang groups （n=12） according to body weight. The normal group was fed with a normal diet， and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h， the aorta was collected. Plaque conditions， pathological changes， levels of total cholesterol （TC）， triglcerides （TG）， low-density lipoprotein-cholesterol （LDL-C）， and high-density lipoprotein-cholesterol （HDL-C）， and the expression of TRPV1， liver X receptor （LXR）， inducible degrader of the low-density lipoprotein receptor （IDOL）， and low-density lipoprotein receptor （LDLR） in the aortic tissue were observed and detected by gross oil red O staining， HE staining， Western blot， immunohistochemistry， and real-time PCR. ResultsCompared with the normal group， the model group presented obvious plaque deposition in the aorta， raised levels of TC， TG， and LDL-C in the serum （P<0.01）， up-regulated expression level of LDLR in the aorta （P<0.01）， lowered level of HDL-C in the serum， and down-regulated expression levels of TRPV1， LXR， and IDOL in the aorta （P<0.05， P<0.01）. Compared with the model group， the positive drug and Renshentang at different doses alleviated AS， elevated the levels of HDL-C， TRPV1， LXR， and IDOL （P<0.05， P<0.01）， while lowering the levels of TC， TG， LDL-C， and LDLR （P<0.05， P<0.01）. ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition， lipid levels， and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

Objective To explore the time-varying pattern of potential symptoms in breast cancer patient before and after chemotherapy,and further analyze its influencing factors,aims to provide reference for clinical nursing practice.Methods 233 cases of breast cancer in a tertiary A hospital in Ningxia from June to October,2023 were selected as the research subjects.By the general information questionnaire and the Chinese version of Anderson Symptom Assessment Scale,the potential change of symptoms of breast cancer patients undergoing chemotherapy 1-3 days before the first chemotherapy(T1,233 cases)and 7-14 days after the third or fourth chemotherapy(T2,225 cases)was analyzed.Results 225 cases of breast cancer patients completed 2 surveys,and their symptom characteristics before and after chemotherapy can be divided into 2 categories:a high symptom troubled group and a low symptom troubled group.The high-symptom troubled group has strong stability,and the probability of maintaining the original group is 85.20％,while the low-symptom troubled group is more inclined to change to the high-symptom troubled group,and the transition probability is 26.60％.Logistic regression analysis showed that the mass was located on the left side,and the patients who obtained disease knowledge mainly through the Internet were more likely to change from the high symptom troubled group to the low symptom troubled group,while the patients who were employed,with unsatisfactory sleep at night,and never exercised were more likely to change from the low symptom troubled group to the high symptom troubled group.Conclusion The symptoms of breast cancer patients before and after chemotherapy are heterogeneous.Patients who are on the job,have unsatisfied sleep at night and never exercise are more likely to change from the low-symptom troubled group to the high-symptom troubled group,which suggests that medical staff should identify potential high-risk groups at an early stage,and make full use of the predictive function of symptom characteristics to carry out individualized management based on the dynamic monitoring of symptoms according to different types of population characteristics,so as to reduce the burden of symptoms and improve their quality of life.

Objective:To explore the correlation between serum nidogen-2 (NID-2) and thoracic aortic calcification in patients with chronic kidney disease (CKD), and construct a risk prediction model based on NID-2 to evaluate its value in predicting the risk of the severe thoracic aortic calcification and cardiovascular and cerebrovascular events in CKD patients.Methods:It was a prospective cohort study. Patients with CKD at stage 3 to 5D in the Zhongda Hospital Affiliated to Southeast University from January 2022 to January 2023 were enrolled. Syngo.via software was used to evaluate the volume of thoracic aortic calcification, and enzyme-linked immunosorbent assay was employed to determine the level of serum NID-2. According to the volume of thoracic aortic calcification, the patients were divided into three groups: no calcification group, mild calcification group and severe calcification group. The top 25% of the patients were defined as no or mild calcification group, and the latter 75% were defined as severe calcification group. The follow-up period was one year. During the follow-up period, cardiovascular and cerebrovascular events, as well as all-cause death among the enrolled patients were recorded. Logistic regression analysis was used to screen the influencing factors of thoracic aortic calcification. Based on the results of logistic regression analysis, a nomogram prediction model was constructed. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve were employed to evaluate the discrimination, calibration and clinical practicality of the nomogram model.Results:A total of 132 patients were included, with 91 males (68.94%) and age of (56.51±16.37) years. There were 60 CKD 3-5 stage patients (non-dialysis, 45.45%) and 72 CKD 5D patients (dialysis, 54.55%). Serum ND-2 levels differed significantly among healthy individuals, dialysis patients and non-dialysis patients ( H=70.651, P<0.001). There was no statistically significant difference in serum NID-2 level between the no or mild calcification group and the severe calcification group in dialysis patients ( Z=350.00, P=0.426). The serum NID-2 level in the severe calcification group was significantly higher than that in the no or mild calcification group in non-dialysis patients ( Z=242.00, P=0.019). In non-dialysis patients, there was a statistically significant correlation between serum NID-2 level and volume of thoracic aortic calcification ( r=0.40, P<0.001). In dialysis patients, there was no statistically significant correlation between serum NID-2 level and volume of each segment of thoracic aortic calcification (all P>0.05). The univariate logistic regression analysis showed that, age, hemoglobin, serum albumin, estimated glomerular filtration rate, NID-2, hypertension, type 2 diabetes mellitus and cerebral infarction were correlated factors of thoracic aortic calcification in non-dialysis patients (all P<0.05). Multivariate logistic regression analysis showed that age ( OR=1.22, 95% CI 1.08-1.50, P=0.010) was an independent correlated factor of thoracic aortic calcification in non-dialysis patients. The above related variables of univariate logistic regression analysis were incorporated into a nomogram to construct a predictive model for severe vascular calcification in non-dialysis patients, yielding an AUC of 0.94 (95% CI 0.89-0.99) in ROC curve, with a sensitivity of 83% and a specificity of 95%. A nomogram model based on above variables for predicting cardiovascular and cerebrovascular events in non-dialysis patients demonstrated an AUC of 0.95 (95% CI 0.90-1.00) in ROC curve, with a sensitivity of 95% and a specificity of 87%. Conclusions:In non-dialysis patients, serum NID-2 level in the severe calcification group is significantly higher than that in the no or mild calcification group. The serum NID-2 is a related factor of thoracic aortic calcification and cardiovascular and cerebrovascular events in non-dialysis patients. The nomogram prediction model constructed by combining NID-2 with age, hemoglobin, serum albumin, estimated glomerular filtration rate, hypertension, type 2 diabetes mellitus and cerebral infarction has a high predictive value for the risk of thoracic aortic calcification as well as cardiovascular and cerebrovascular events in non-dialysis patients.

Objective:To evaluate the clinical outcomes of applying an enhanced workflow in robotic-assisted total hip revision arthroplasty.Methods:A retrospective study was conducted to analyze the 25 consecutive patients who had undergone robotic-assisted total hip revision arthroplasty in which an enhanced workflow was applied at Department of Orthopaedic Surgery, Beijing Jishuitan Hospital from September 2021 to October 2024. The cohort consisted of 8 males and 17 females with an age of (64.0±12.8) years. The left side was affected in 18 cases and the right side in 7 cases. The time from initial total hip arthroplasty to revision was (159.6±86.7) months. In all patients, no significant difference was found in the preoperative femoral cortical thickness between the healthy and the affected sides. The enhanced workflow included preoperative CT modeling and planning, intraoperative registration, prosthetic removal and reconstruction, and verification of prosthesis position. A total of 18 patients underwent total hip revision involving both the acetabular and the femoral sides; 6 patients underwent simple acetabular reconstruction with retention of the original femoral stem and replacement of the femoral head; 1 patient underwent femoral revision with retention of the acetabular cup and replacement of the acetabular liner. The operative time, intraoperative blood loss, modified Harris Hip Score (mHHS) and visual analogue scale (VAS) for hip pain at the final follow-up, and follow-up complications were recorded.Results:All patients successfully completed robotic registration during surgery, with no case of intraoperative robotic termination. For the 25 patients, the operative time was (152.2±43.8) minutes, the intraoperative blood loss 600 (400, 1,000) mL, and the follow-up time 12.0 (6.0, 31.5) months. At the final follow-up, their mHHS improved from 66.0 (26.4, 75.6) points preoperatively to 93.5 (80.3, 98.9) points, and their VAS pain score decreased from 5.0 (3.0, 7.0) points preoperatively to 0.0 (0.0, 2.0) point ( P<0.05). Follow-ups revealed no case of reoperation, prosthetic loosening, joint dislocation, periprosthetic infection, or periprosthetic fracture. Conclusion:The enhanced workflow can achieve satisfactory outcomes in robotic-assisted total hip revision for patients with adequate proximal femoral bone stock.

Objective:To report the 5-year survival outcomes and recurrence patterns of robotic total gastrectomy (RTG) for locally advanced proximal gastric cancer in order to provide more valuable long-term follow-up results for clinical practice.Methods:This was a prospective, single-arm, open-label clinical trial (FUGES-014; Clinical-Trials.gov, NCT03524287). Patients with locally advanced proximal gastric cancer who underwent RTG at Fujian Medical University Union Hospital from March 5, 2018, to February 10, 2020, were included in the analysis. To evaluate the long-term efficacy of RTG in the most objective manner possible, we performed a propensity score-matched (1∶2) comparative analysis with historical control patients who had undergone laparoscopic total gastrectomy (LTG) from the FUGES-002 study (ClinicalTrials.gov, NCT02333721) in which the 5-year disease-free survival (DFS), 5-year overall survival (OS), and recurrence patterns were compared between the two groups.Results:Prior to matching, there were 48 cases in the RTG group and 263 cases in the LTG group; patients in the LTG group had more advanced cT and pT stages ( P=0.044 and 0.006, respectively) compared to the RTG group. After matching, there were 48 cases in the RTG group and 96 cases in the LTG group; however, no statistically significant differences were observed in the baseline clinical characteristics between the two groups (all P>0.05). Both groups had a median follow-up of 72 months. The 5-year DFS rates were 75.0% (95%CI: 63.7%- 88.3%) in the RTG group and 61.4% (95%CI: 52.5%-72.0%) in the LTG group ( P=0.116). Similarly, the 5-year OS rates were 79.2% (95%CI: 68.5%-91.5%) and 64.6% (95%CI: 55.7%-74.9%) in the RTG and LTG groups, respectively ( P=0.100). Within 5 years after surgery, tumor recurrence occurred in 10 patients (20.8%) in the RTG group and 33 patients (34.4%) in the LTG group ( P=0.124), and peritoneal recurrence was the predominant pattern in both groups (8.3%[4/48] vs. 10.4%[10/96]; risk difference: -0.02, P=0.554). Gastric cancer-related death was the predominant cause of death in both groups (16.7% [8/48] vs. 31.2% [30/96]; risk difference: -0.15, P=0.064). Among patients stratified by different pathological stages, no statistically significant differences were found in DFS, OS, or recurrence rates between the RTG and LTG groups (all P>0.05). Conclusions:We find the long-term oncological outcomes of RTG for locally advanced proximal gastric cancer to be noninferior to those of LTG. RTG should therefore be considered as a valid option for standardized minimally invasive surgery for locally advanced proximal gastric cancer.

Objective To explore the correlation between nap frequency and sleep duration and the risk of carotid atherosclerosis(CAS)in the middle-aged and elderly people in Guangzhou.Methods A retrospective study was conducted to select 1170middle-aged and elderly patients over 50 years who were enrolled in"Guangzhou Biobank Cohort-Cardiovascular Disease Subcohort"from Sep-tember 2006 to March 2008.The general data of the subjects were collected,and the intima-media thickness of common carotid artery,CCA-IMT was measured by color Doppler ultrasound.Logistic regression analysis was used to evaluate the correlation between nap fre-quency and sleep duration and the risk of CAS.Results After adjusting for potential confounding factors such as gender,age,body mass index(BMI),waist-to-hip ratio(WHR),physical activity level,smoking,alcohol consumption,and diabetes,the study found that compared with those who never nappers,Daily nappers had a higher risk of CAS[adjusted Exp(β)=2.095,95％CI:1.823-2.407,P＜0.001].In addition,this study observed a"U-shaped"association between sleep duration and CAS prevalence.Further studies found that compared with those who slept for 6h per day,those who slept for ≤5h,8h and≥10h had a significantly increased risk of CAS(adjusted OR=1.420,95％CI:1.117-1.805,P＜0.001;OR=1.356,95％CI:1.142-1.610,P＜0.001;OR=1.537,95％CI:1.156-2.044,P＜0.01).Conclusion Daily napping and short or long sleep duration may increase the risk of CAS.It is recommen-ded to reduce the nap frequency and maintain the appropriate sleep duration in order to reduce the incidence of CAS.