Objective:To investigate the risk factors for kidney injury during anti-retroviral therapy (ART) with zidovudine (AZT) or tenofovir disoproxil fumarate (TDF) in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients, and to construct and validate a prediction model for the risk of kidney injury in HIV/AIDS patients based on a nomogram.Methods:A total of 923 HIV/AIDS patients admitted to Liuzhou People′s Hospital between January 1st, 2004 and December 31st, 2020 were included in this study. The modeling set (647 cases) and the validation set (276 cases) were divided in a 7∶3 ratio. Risk factors were screened using the least absolute shrinkage and selection operator (LASSO) regression analysis, and a nomogram prediction model for renal impairment risk in HIV/AIDS patients was constructed based on the selected variables. The model′s predictive performance was assessed by calculating the area under the curve (AUC) using the receiver operating characteristics curve (ROC curve). The performance of this model was evaluated using calibration curves. The clinical utility of the model was assessed using decision curve analysis (DCA).Results:Among 923 HIV/AIDS patients, there were 91 cases with kidney injury, including 67 in the modeling set and 24 in the validation set. AZT was used in 29 cases, and TDF was used in 62 cases. LASSO regression analysis was employed to screen seven non-zero variables, including age, ART regimen, baseline estimated glomerular filtration rate (eGFR), baseline CD4 + T lymphocyte count, baseline human immunodeficiency virus (HIV) RNA, baseline hemoglobin, and baseline aspartate aminotransferase (AST), their LASSO regression coefficient were 1.296, 0.250, 1.443, 0.240, 0.120, 0.395, and 0.002, respectively. Based on these variables, a visual nomogram model was constructed and subsequently validated. Through ROC curve analysis, the AUC for the modeling set was 0.826 (95% confidence interval ( CI) 0.767 to 0.884), with a sensitivity of 0.731 and a specificity of 0.809. For the validation set, the AUC was 0.872 (95% CI 0.807 to 0.956), with a sensitivity of 0.875 and a specificity of 0.778. The calibration curve results for the modeling set showed a mean absolute error (MAE) of 0.012 and a consistency index of 0.826, while the validation set had an MAE of 0.021 and a consistency index of 0.872. These results indicated that the model had a high goodness-of-fit, excellent calibration performance, and was reliable and stable. When the risk threshold for the modeling set ranged from 2% to 73%, the model demonstrated favorable net benefits, indicating its excellent clinical utility. Conclusion:The nomogram-based risk prediction model for kidney injury in HIV/AIDS patients is constructed using seven variables including age, ART regimen, baseline eGFR, baseline CD4 + T lymphocyte count, baseline HIV RNA, baseline hemoglobin, and baseline AST, which provides a valuable tool for early identification of individuals at risk of kidney injury and supports timely clinical interventions.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Objective:This study aimed to investigate the morphological and functional changes of jejunal and ileal epithelium in aged mice using 3D organoid culture, to elucidate the age-related alterations in epithelial function across different regions of the intestine.Methods:The C57BL/6J male mice were divided into two groups: a young group(5 months)and an old group(24 months).Epithelial tissues from the jejunum and ileum were harvested, and the jejunal and ileal epithelial crypt units were separated for 3D organoid culture in vitro.Histological analyses, including H&E and PAS staining, immunofluorescence staining, and quantitative PCR, were employed to assess changes in crypt depth, villi length, goblet cell numbers, inflammation, and mucosal barrier function in the aged mice.Results:With aging, the crypt of jejunum became deeper and the ratio of villi length to crypt depth decreased, while the villi length of ileum became longer and the ratio of villi length to crypt depth increased.The rate of organoid formation in jejunal and ileal crypts and the number of crypto-like regions of organoid formation were significantly decreased in the aged mice, along with a decrease in the expression of the stem cell proliferation marker Ki67.The inflammation of the jejunal and ileal epithelium increased in the aged mice, and the mechanical barrier function of the epithelial mucosa was enhanced.Conclusions:In aged mice, both the jejunal and ileal epithelium exhibited similar changes in stem cell proliferation, inflammation, and mucosal mechanical barrier function, though the changes in villus length and crypt depth ratio were opposite.This study provides a foundation for further investigation of the differences in jejunal and ileal epithelial function and its potential mechanisms during aging.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

Objective:This study aimed to investigate the morphological and functional changes of jejunal and ileal epithelium in aged mice using 3D organoid culture, to elucidate the age-related alterations in epithelial function across different regions of the intestine.Methods:The C57BL/6J male mice were divided into two groups: a young group(5 months)and an old group(24 months).Epithelial tissues from the jejunum and ileum were harvested, and the jejunal and ileal epithelial crypt units were separated for 3D organoid culture in vitro.Histological analyses, including H&E and PAS staining, immunofluorescence staining, and quantitative PCR, were employed to assess changes in crypt depth, villi length, goblet cell numbers, inflammation, and mucosal barrier function in the aged mice.Results:With aging, the crypt of jejunum became deeper and the ratio of villi length to crypt depth decreased, while the villi length of ileum became longer and the ratio of villi length to crypt depth increased.The rate of organoid formation in jejunal and ileal crypts and the number of crypto-like regions of organoid formation were significantly decreased in the aged mice, along with a decrease in the expression of the stem cell proliferation marker Ki67.The inflammation of the jejunal and ileal epithelium increased in the aged mice, and the mechanical barrier function of the epithelial mucosa was enhanced.Conclusions:In aged mice, both the jejunal and ileal epithelium exhibited similar changes in stem cell proliferation, inflammation, and mucosal mechanical barrier function, though the changes in villus length and crypt depth ratio were opposite.This study provides a foundation for further investigation of the differences in jejunal and ileal epithelial function and its potential mechanisms during aging.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Objective:To investigate the risk factors for kidney injury during anti-retroviral therapy (ART) with zidovudine (AZT) or tenofovir disoproxil fumarate (TDF) in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients, and to construct and validate a prediction model for the risk of kidney injury in HIV/AIDS patients based on a nomogram.Methods:A total of 923 HIV/AIDS patients admitted to Liuzhou People′s Hospital between January 1st, 2004 and December 31st, 2020 were included in this study. The modeling set (647 cases) and the validation set (276 cases) were divided in a 7∶3 ratio. Risk factors were screened using the least absolute shrinkage and selection operator (LASSO) regression analysis, and a nomogram prediction model for renal impairment risk in HIV/AIDS patients was constructed based on the selected variables. The model′s predictive performance was assessed by calculating the area under the curve (AUC) using the receiver operating characteristics curve (ROC curve). The performance of this model was evaluated using calibration curves. The clinical utility of the model was assessed using decision curve analysis (DCA).Results:Among 923 HIV/AIDS patients, there were 91 cases with kidney injury, including 67 in the modeling set and 24 in the validation set. AZT was used in 29 cases, and TDF was used in 62 cases. LASSO regression analysis was employed to screen seven non-zero variables, including age, ART regimen, baseline estimated glomerular filtration rate (eGFR), baseline CD4 + T lymphocyte count, baseline human immunodeficiency virus (HIV) RNA, baseline hemoglobin, and baseline aspartate aminotransferase (AST), their LASSO regression coefficient were 1.296, 0.250, 1.443, 0.240, 0.120, 0.395, and 0.002, respectively. Based on these variables, a visual nomogram model was constructed and subsequently validated. Through ROC curve analysis, the AUC for the modeling set was 0.826 (95% confidence interval ( CI) 0.767 to 0.884), with a sensitivity of 0.731 and a specificity of 0.809. For the validation set, the AUC was 0.872 (95% CI 0.807 to 0.956), with a sensitivity of 0.875 and a specificity of 0.778. The calibration curve results for the modeling set showed a mean absolute error (MAE) of 0.012 and a consistency index of 0.826, while the validation set had an MAE of 0.021 and a consistency index of 0.872. These results indicated that the model had a high goodness-of-fit, excellent calibration performance, and was reliable and stable. When the risk threshold for the modeling set ranged from 2% to 73%, the model demonstrated favorable net benefits, indicating its excellent clinical utility. Conclusion:The nomogram-based risk prediction model for kidney injury in HIV/AIDS patients is constructed using seven variables including age, ART regimen, baseline eGFR, baseline CD4 + T lymphocyte count, baseline HIV RNA, baseline hemoglobin, and baseline AST, which provides a valuable tool for early identification of individuals at risk of kidney injury and supports timely clinical interventions.