Objective To explore the change pattern of quantitative parameters in contrast-enhanced computed tomography (CECT) scans during the cortical and nephrographic phases in patients with clear cell renal cell carcinoma (ccRCC), evaluate the diagnostic efficiency of these quantitative parameters in predicting the pathological grade of ccRCC preoperatively, and provide imaging reference for clinically evaluating preoperative disease severity and formulating individualized therapeutic regimens. Methods A retrospective analysis was performed on the clinical data of 84 patients with ccRCC treated in our hospital between September 2022 and September 2024. According to the World Health Organization/International Society of Urological Pathology (WHO/ISUP) pathological grading system, patients were divided into a high-grade group (n = 32) and a low-grade group (n = 52). CECT features and quantitative parameters were compared between the two groups. The relationships between CECT quantitative parameters and pathological grading in ccRCC patients were analyzed using Spearman correlation. The diagnostic value of these parameters for preoperative pathological grading was evaluated using receiver operating characteristic curves. Results The maximum tumor diameter and the proportion of tumors with blurred margins were higher in the high-grade group than in the low-grade group (P<0.05). The CT values, net enhancement values, and enhancement rates during both the cortical and nephrographic phases were lower in the high-grade group than in the low-grade group (P<0.05). Spearman correlation analysis showed that the CT values, net enhancement values, and enhancement rates during both the cortical and nephrographic phases were negatively correlated with preoperative pathological grades in ccRCC patients (P<0.05). Receiver operating characteristic curve analysis revealed that the area under the curve for preoperative pathological grading using the combination of cortical phase CT value, cortical phase net enhancement value, cortical phase enhancement rate, nephrographic phase CT value, nephrographic phase net enhancement value, and nephrographic phase enhancement rate was 0.912, which was higher than the areas for any individual parameter used alone (0.770, 0.748, 0.763, 0.751, 0.739, and 0.718, respectively; P<0.05). The sensitivity, specificity, and 95% confidence interval for the parameters used in combination were 96.88%, 69.23%, and 0.853-0.970, respectively. Conclusion CECT quantitative parameters were negatively correlated with pathological grades in patients with single ccRCC and demonstrated high diagnostic efficiency for pathological grading, providing a reference for clinical treatment planning.

ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

Objective To explore the clinical efficacy of plasma exchange (PE) and double-filtration plasmapheresis (DFPP) pretreatment regimens for high-titer ABO-incompatible kidney transplantation (ABOi-KT). Methods A retrospective analysis was conducted on 31 cases of ABOi-KT with a follow-up period ≥1 year admitted to Zhongshan Hospital Affiliated to Fudan University from April 2016 to August 2025. The efficacy differences between the PE combined with rituximab (RTX) + oral triple immunosuppressive regimen and the DFPP combined with RTX + oral triple immunosuppressive regimen were compared and analyzed. The titers of blood group antibodies and serum creatinine levels before and after the operation were monitored. The survival curves and cumulative risk occurrence curves were plotted using the Kaplan-Meier method. The survival rates of recipients and transplanted kidneys and the occurrence of complications were analyzed. Results Both the PE regimen and the DFPP regimen may effectively reduce the preoperative blood group antibody titer of the recipients to ≤1∶16. The one-year survival rate of the recipients and the transplanted kidneys both reached 100% after the operation. The postoperative serum creatinine levels of recipients who received the DFPP regimen were lower and more stable. There was no statistically significant difference in the incidence of complications between the two regimens during the same follow-up period. Conclusions Both the PE and DFPP regimens are effective pretreatment regimens for ABOi-KT. The DFPP regimen has more advantages in reducing treatment operations, lowering drug dosage and maintaining the stability of postoperative renal function. For recipients with a high initial antibody titer (≥ 1∶32), individualized determination of the number and frequency of plasma processing for pretreatment may achieve ideal therapeutic effects.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

This study investigated the therapeutic effects and mechanisms of Modified Yiyi Fuzi Baijiang Powder on ulcerative colitis(UC) in rats from the perspective of dampness. SD rats were randomly allocated into six groups(n=10): control, model, mesalazine, and Modified Yiyi Fuzi Baijiang Powder at low(3.96 g·kg~(-1)·d~(-1)), medium(7.92 g·kg~(-1)·d~(-1)), and high(15.84 g·kg~(-1)·d~(-1)) doses. UC was induced in all groups except the control by administration with 3% dextran sulfate sodium(DSS) solution for 7 days. The disease activity index(DAI) was recorded, and the colon tissue was collected for analysis. Histopathological changes were assessed by hematoxylin-eosin staining. Serum levels of D-lactic acid(D-LA) and diamine oxidase(DAO) were measured by ELISA. Immunohistochemistry and PCR were employed to evaluate the expression of aquaporins(AQP3, AQP4) and tight junction proteins [zonula occludens-1(ZO-1) and occludin] at both protein and mRNA levels. Compared with the control group, the model group showed an increased DAI scores(P<0.05), intestinal mucosal damage, elevated serum levels of DAO and D-LA(P<0.05), and decreased expression of AQP3, AQP4, ZO-1, and occludin(P<0.05). Treatment with Modified Yiyi Fuzi Baijiang Powder reduced the DAI scores(P<0.05), lowered the serum levels of D-LA and DAO(P<0.05), and upregulated the expression of AQP3, AQP4, ZO-1, and occludin at both protein and mRNA levels compared with the model group. These findings suggest that Modified Yiyi Fuzi Baijiang Powder exerts therapeutic effects on UC by reducing the intestinal mucosal permeability, promoting colonic mucosal repair, and regulating abnormal intestinal water metabolism, which may involve the upregulation of AQP3 and AQP4 expression.
Animals ; Colitis, Ulcerative/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Rats ; Intestinal Mucosa/metabolism* ; Male ; Aquaporin 3/metabolism* ; Aquaporin 4/metabolism* ; Permeability/drug effects* ; Humans ; Powders ; Intestinal Barrier Function

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population aging. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.
Humans ; Male ; Female ; Incidence ; Fractures, Bone/epidemiology* ; Middle Aged ; Adult ; Global Health ; Aged ; Global Burden of Disease ; Adolescent ; Child ; Young Adult ; Foot Injuries/epidemiology* ; Cost of Illness ; Child, Preschool ; Aged, 80 and over ; Infant

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.
Male ; Humans ; Autophagy/physiology* ; Apoptosis/physiology* ; Erectile Dysfunction/physiopathology* ; Fibrosis ; Penis/pathology* ; Animals ; Endothelial Cells/pathology* ; Myocytes, Smooth Muscle/pathology*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To investigate the clinical and immunological features of children with primary immune thrombocytopenia (pITP) or connective tissue disease (CTD) with thrombocytopenia as the initial manifestation at initial diagnosis, and to provide a basis for early differentiation. METHODS: A retrospective study was performed on 236 children with pITP (pITP group) or CTD with thrombocytopenia as the initial manifestation (CTD-TP group) who were admitted from January 2019 to August 2024. Clinical and immunological indicators were compared between the two groups to identify potential influencing factors for early differentiation and their discriminative validity. RESULTS: Compared with the pITP group, the CTD-TP group had a significantly older age of onset and significantly lower leukocyte count, eosinophil count, lymphocyte count, and complement C4 level (P<0.05), as well as significantly higher levels of C-reactive protein, IgE, and IgM (P<0.05). The logistic regression analysis showed that age, IgE, IgM, total B cells, and complement C4 were predictive factors for early differentiation between pITP and CTD-TP (P<0.05). The receiver operating characteristic curve analysis showed that a combination of these five factors had a good discriminative validity, with an area under the curve of 0.944. The correlation analysis showed a negative correlation between IgG and platelet count in the pITP group (r_s=-0.363, P<0.05) and a positive correlation between NK cells and platelet count in the CTD-TP group (r_s=0.713, P<0.05). CONCLUSIONS There is heterogeneity in the clinical and immunological indicators between children with pITP and CTD-TP at initial diagnosis, and these research findings can help with the early differentiation between the two diseases.
Purpura, Thrombocytopenic, Idiopathic/immunology* ; Diagnosis, Differential ; Connective Tissue Diseases/immunology* ; Retrospective Studies ; Early Diagnosis ; Age of Onset ; Leukocyte Count ; Complement C4/immunology* ; C-Reactive Protein/immunology* ; Immunoglobulin E/immunology* ; Immunoglobulin M/immunology* ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; Biomarkers/blood*