OBJECTIVES: To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting. RESULTS: The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC. CONCLUSIONS DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
Animals ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Diabetic Nephropathies/drug therapy* ; Receptor, Notch1/metabolism* ; Kidney/blood supply* ; Diabetes Mellitus, Experimental ; Down-Regulation ; Endothelium, Vascular/metabolism* ; Nuclear Proteins/metabolism*

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

Objective:To investigate the rate-limiting steps of hand-assisted laparoscopic donor nephrectomy, analyze the relevant factors affecting surgical difficulty, and subsequently construct a mathematical model to predict the difficulty of the procedure preoperatively.Methods:A retrospective study was conducted on 100 kidney donors who underwent hand-assisted laparoscopic donor nephrectomy performed by the same surgeon at Beijing Friendship Hospital, Capital Medical University from January 2021 to January 2024. Preoperative demographic data, imaging findings, general condition, donor kidney size, and postoperative complications were collected and analyzed. The surgeon′s subjective rating (1-3 points) was used as a quantitative measure of surgical difficulty. ANOVA and Chi-square tests were employed to explore the differences in postoperative complications, recovery, operative time, and intraoperative blood loss among groups with varying levels of difficulty. The main procedure was divided into four steps (excluding abdominal closure): Trocar placement, renal hilar dissection, perinephric dissection, and kidney retrieval. The time for each step and the total operative time were recorded. Pearson correlation test was used to analyze the relationship between each step and the total operative time, and ANOVA test was used to assess the time differences between steps and to determine if the time for the same step varied across different difficulty subgroups, thereby identifying the rate-limiting step of hand-assisted laparoscopic donor nephrectomy. In terms of the risk factors influencing the difficulty of surgery, Pearson and Spearman correlation tests were used to investigate the relationship between preoperative donor data and surgical difficulty scores, and a predictive model was constructed using multiple linear regression. Finally, the model was internally and externally validated to confirm its accuracy and effectiveness.Results:As the surgical difficulty increased (groups 1, 2, and 3), the postoperative drainage tube duration was correspondingly prolonged [(5.92±1.48) d, (8.00±1.75) d, and (11.88±4.45) d, respectively, P<0.05], and the severity of postoperative complications also significantly increased (the incidence of Clavien-Dindo grade ≥2 was 5.66%, 31.82% and 64.00%, respectively, P<0.01). In the analysis of rate-limiting steps, the time taken for all steps, except for Trocar placement, showed significant differences among the difficulty subgroups ( P<0.001). However, the average time for renal hilar dissection was (19.82±5.65) min, which was significantly longer than the other steps ( P<0.001). Therefore, renal hilar dissection was identified as the rate-limiting step of hand-assisted laparoscopic donor nephrectomy. In terms of the influencing factors of surgical difficulty, donor obesity, kidney width, abdominal anteroposterior sagittal diameter, number of renal arteries, distance from renal artery bifurcation to the abdominal aorta, degree of renal artery calcification, and mayo adhesive probability (MAP) score were all correlated with the surgical difficulty score ( P<0.05). However, multiple linear regression analysis revealed that only the number of renal arteries and the MAP score were the independent risk factors for higher surgical difficulty of hand-assisted laparoscopic donor nephrectomy. The predictive equation was: surgical difficulty=0.649×number of renal arteries+ 0.770×MAP score. Both internal and external validation confirmed the model's good accuracy. Conclusions:This study established a reliable and objective predictive model for the difficulty of hand-assisted laparoscopic donor nephrectomy based on the number of renal arteries and the MAP score. Renal hilar dissection was identified as the rate-limiting step of the procedure. This provides a reference for selecting an appropriate surgeon based on the predicted surgical difficulty.

Objective: To understand the level of nutritional literacy and its influencing factors among schoolage children in grades 4-9 in Guizhou Province, and to explore the relationship between nutritional literacy and physical health, so as to provide reference for improving nutritional literacy and physical health of schoolage children. Methods: Using multistage stratified cluster sampling method, 1 155 schoolage children in grades 4-6 in elementary school and grades 7-9 in secondary schools in three prefectural and municipal cities of Guizhou Province (Zunyi, Tongren, and Bijie) were sampled from February to July 2023, and were surveyed for nutritional literacy by using the "Food and Nutritional Literacy Questionnaire for Chinese Schoolage Children", and their physical health data (data on body measurement indicators, such as height, weight, lung capacity, and vertical jump) were obtained from the physical health surveillance platform. Pearson correlation analysis and binary Logistic regression modeling were used to explore the association between nutritional literacy and physical health. Results: The nutritional literacy score of the study population was (63.50±8.63), and the scores of each level of nutritional literacy in descending order were interactivity (66.09±13.99), functionality (63.84±8.80), and criticism (61.15±14.65); and the scores of cognitive domain of nutritional literacy, and skill domain were (64.71±10.77) (62.97±9.21); food selection, food preparation, and food intake dimension scores were (64.68±13.52) (56.39±12.17) (63.63±10.04), respectively. Differences in the total nutritional literacy scores of schoolaged children who were only children or not, by gender, ethnicity, grade level, primary caregiver, primary caregivers education, and family economic situation were statistically significant (t/F=2.88, -3.28, 5.02, 18.32, 4.67, 32.47, 32.53, P<0.05); the physical health pass rate was 85.8%, and the mean scores of the total physical health score, physical form, physical function, and physical fitness dimensions were (71.86±10.52) (93.29±12.06) (72.12±14.42) (67.26±13.13), respectively; after controlling for confounders, the nutritional literacy scores were positively correlated with physical health (OR=1.03, 95%CI=1.01-1.05, P<0.05). Conclusion Nutritional literacy scores of schoolage children in grades 4-9 in Guizhou Province are low, and there is a positive correlation between nutritional literacy and physical health in this school age children.

Objective To identify the influencing factors of operation time of hand-assisted laparoscopic living donor nephrectomy, and to analyze the relationship between influencing factors and the severity of postoperative complications. Methods Clinical data of 91 donors who underwent hand-assisted laparoscopic nephrectomy were retrospectively analyzed. The correlation between preoperative baseline data of donors and operation time was analyzed. The relationship between operation time and postoperative complications was assessed and the threshold of operation time was determined. Results Multiple donor renal arteries, thick perirenal and posterior renal fat, metabolic syndrome, high Mayo adhesive probability (MAP) score and Clavien-Dindo score prolonged the operation time. By analyzing the receiver operating characteristic (ROC) curve, we found that when the operation time was ≥138 min, the incidence of postoperative complications of donors was significantly increased (P<0.05). Conclusions For donors with multiple renal arteries, thick perirenal and posterior renal fat, metabolic syndrome and high MAP score and Clavien-Dindo score, experienced surgeons should be selected to make adequate preoperative preparation and pay close attention after surgery, so as to timely detect postoperative complications and reduce the severity of complications, enhance clinical prognosis of the donors.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

Objective:To investigate the clinicopathological characteristics of dedifferentiated endometrial carcinoma/undifferentiated endometrial carcinoma (DDEC/UDEC) with loss of expression of SMARCA4.Methods:A total of 10 cases with loss of expression of SMARCA4 were diagnosed at Fujian Cancer Hospital between January 2019 and December 2023. A retrospective analysis was conducted on the clinical characteristics, morphology, immunophenotype, molecular classification, and prognosis.Results:(1) Clinical characteristics: among 10 cases of DDEC/UDEC with loss of expression of SMARCA4, the patients′ age ranged from 48 to 65 years, with a median age of 56 years.Five cases were classified as International Federation of Gynecology and Obstetrics (FIGO) stages Ⅰ-Ⅱ, while the remaining five were categorized as stages Ⅲ-Ⅳ. (2) Pathological features: tumor cells exhibited poor cell adhesion, with common intravascular tumor emboli (8/10), occasional vacuolated nuclei (6/10), rhabdoid cells (4/10), and starry sky phenomenon formed by tissue cell phagocytosis apoptosis bodies or fragments (4/10). Six cases (6/10) showed loss of mismatch repair (MMR) protein expression, two cases (2/10) exhibited p53 mutant expression, and five cases (5/10) tested positive for programmed cell death ligand 1 (PD-L1). (3) Molecular subtyping: molecular subtyping revealed POLEmut in 1 case (1/10), mismatch repair deficient (MMR-d) in 5 cases (5/10), p53 abn in 1 case (1/10), and no specific molecular profile (NSMP) in 3 cases (3/10). (4) Prognosis: the follow-up period ranged from 7 to 42 months, with a median of 20 months. Five patients succumbed to the tumor, whereas the remaining five exhibited no recurrence during subsequent postoperative evaluations. The 2-year progression-free survival rates and overall survival rates were 58.3% and 52.5%, respectively.Conclusions:Loss of expression of SMARCA4 occurs in approximately 1/5 of DDEC/UDEC, which presents with an aggressive clinical course and a poor prognosis. About half of them show MMR protein loss expression and PD-L1 positive expression, suggesting that there might be benefit from treatment with immune checkpoint inhibitors.

Objective To investigate the correlation between amide proton transfer-weighted(APTw)value derived from APTw imaging and Ki-67 expression in hepatocellular carcinoma.Methods Sixty patients with hepatic occupations underwent preoperative upper abdominal MRI scanning,including APTw and diffusion weighted imaging(DWI)sequences.Thirty-two patients with hepatocellular carcinoma proved by pathological results were enrolled in the prospective study.The APTw and apparent diffusion coefficient(ADC)values of the lesions were measured from the corresponding APTw and ADC images,respectively.Mann-Whitney U test or independent sample t test was used to analyze the differences in APTw and ADC values between the high and low Ki-67 expression groups.Pearson correlation analysis was used to evaluate the correlation between APTw value,ADC value and Ki-67 expression level of hepatocellular carcinoma.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of amide proton transfer(APT)parameter in differentiating high and low Ki-67 expression groups.Results The APTw values of high Ki-67 expression group(n=24)was higher than that of low Ki-67 expression group(n=8)[(1.33±0.77)％vs(0.64±0.58)％,P=0.026].There was no significant difference in ADC values between the two groups(0.82×10-3 mm2/s vs 0.86×10-3 mm2/s,P=0.679).The APTw values were positively correlated with Ki-67 expression(r=0.377,P=0.035),and the area under the curve(AUC)of APTw value＞1.24％for the diagnosis of high Ki-67 expression was 0.794,with a sensitivity of 67％and a specificity of 88％.Conclusion The APTw value of hepatocellular carcinoma is positively correlated with Ki-67 expression,which has certain diagnostic value for predicting the expression status of Ki-67.