Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective:To explore clinical and genetic features of persistent asymptomatic microscopic hematuria in children.Methods:A retrospective case analysis of 135 individuals admitted to Xi ′an Children′s Hospital with persistent asymptomatic microscopic haematuria between January 2016 to December 2023 was conducted. The demographic characteristics, kidney pathology and gene results of 135 individuals were analyzed. One hundred and thirty-five individuals were divided into 2 groups (positive group and negative group) according to family history of glomerulogenic hematuria in first-degree relatives. The differences of hematuria remission, proteinuria and gene variation were compared between the 2 groups. Two independent sample t test, Wilcoxon rank sum test, Pearson Chi-square, Yates′ corrected Chi-squared test or Fisher exact test were used for comparison between groups. Results:All 135 children, with 48 males and 87 females, were 8.5 (6.5, 9.5) years old at first presentation. Kidney biopsy was performed in 73 cases (54.1%). Kidney pathology showed mild lesions in 41 cases (56.2%), thin basement membrane disease (TBMD) in 24 cases (32.9%), typical pathological features of Alport syndrome in 5 cases (6.8%), and other manifestations in 3 cases (4.1%). The positive group comprised 52 individuals, whereas the negative group consisted of 83 individuals. The positive group demonstrated a higher susceptibility in proteinuria and gene variation, while the negative group exhibited a greater rate of hematuria remission ( χ2=5.00, 5.27, 8.52, all P<0.05). Whole exome sequencing was performed in 80 individuals and 18 individuals (22.5%) had a pathogenic or likely pathogenic variant in COL4A3-5. COL4A5 was the most common gene afected, accounting for 11 cases. The 135 individuals were followed up for 4.2 (2.9, 5.1) years, of which 31 cases (22.9%) had complete hematuria remission at 2.1 (1.4, 2.7) years. Up to March 2024, there were also 7 individuals (5.2%) with varying degrees of proteinuria, and 3 individuals (2.2%) with proteinuria progressed to chronic kidney insufficiency. Conclusions:The most common kidney pathological types in children with persistent asymptomatic microscopic hematuria are minor lesions and TBMD. Children with microscopic hematuria whose first-degree relatives have a family history of hematuria are more likely to have proteinuria and gene variants. COL4A3-5 genetic screening could be considered a priority in these children.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Objective:To explore clinical and genetic features of persistent asymptomatic microscopic hematuria in children.Methods:A retrospective case analysis of 135 individuals admitted to Xi ′an Children′s Hospital with persistent asymptomatic microscopic haematuria between January 2016 to December 2023 was conducted. The demographic characteristics, kidney pathology and gene results of 135 individuals were analyzed. One hundred and thirty-five individuals were divided into 2 groups (positive group and negative group) according to family history of glomerulogenic hematuria in first-degree relatives. The differences of hematuria remission, proteinuria and gene variation were compared between the 2 groups. Two independent sample t test, Wilcoxon rank sum test, Pearson Chi-square, Yates′ corrected Chi-squared test or Fisher exact test were used for comparison between groups. Results:All 135 children, with 48 males and 87 females, were 8.5 (6.5, 9.5) years old at first presentation. Kidney biopsy was performed in 73 cases (54.1%). Kidney pathology showed mild lesions in 41 cases (56.2%), thin basement membrane disease (TBMD) in 24 cases (32.9%), typical pathological features of Alport syndrome in 5 cases (6.8%), and other manifestations in 3 cases (4.1%). The positive group comprised 52 individuals, whereas the negative group consisted of 83 individuals. The positive group demonstrated a higher susceptibility in proteinuria and gene variation, while the negative group exhibited a greater rate of hematuria remission ( χ2=5.00, 5.27, 8.52, all P<0.05). Whole exome sequencing was performed in 80 individuals and 18 individuals (22.5%) had a pathogenic or likely pathogenic variant in COL4A3-5. COL4A5 was the most common gene afected, accounting for 11 cases. The 135 individuals were followed up for 4.2 (2.9, 5.1) years, of which 31 cases (22.9%) had complete hematuria remission at 2.1 (1.4, 2.7) years. Up to March 2024, there were also 7 individuals (5.2%) with varying degrees of proteinuria, and 3 individuals (2.2%) with proteinuria progressed to chronic kidney insufficiency. Conclusions:The most common kidney pathological types in children with persistent asymptomatic microscopic hematuria are minor lesions and TBMD. Children with microscopic hematuria whose first-degree relatives have a family history of hematuria are more likely to have proteinuria and gene variants. COL4A3-5 genetic screening could be considered a priority in these children.

Objectives:To identify the two-dimensional speckle tracking imaging (2D-STI)-derived longitudinal strain indices that reflect the myocardial functional characteristics of patients with apical hypertrophic cardiomyopathy (AHCM). Methods:This retrospective study included 30 patients with typical AHCM diagnosed at the First Affiliated Hospital of Fujian Medical University from January 2015 to May 2019 (AHCM group),35 patients with essential hypertensive left ventricular hypertrophy (HTLVH group),and 45 healthy volunteers (normal control group) were also included.Two-dimensional echocardiography was used to measure the cardiac chamber size and wall thickness,and 2D-STI was used to analyze the longitudinal strain during the left ventricular systolic phase,the global longitudinal strain (GLS) and the longitudinal strain of the apical,mid,and basal segments (LSA,LSM,LSB) were assessed.The ratios of the apical to the overall and other segmental longitudinal strains were used as the apical relative longitudinal strain indices,including the apical to basal longitudinal strain ratio (ABLR,LSA/LSB),the apical to global longitudinal strain ratio (AGLR,LSA/GLS),and the apical to basal-mid segment longitudinal strain ratio (ABMLR,LSA/[LSB+LSM]). Results:GLS was significantly lower in the AHCM group and HTLVH group than in the normal control group (both P<0.05),and was similar between the AHCM group and HTLVH group (P>0.05).The LSA,LSM,and LSB were also significantly lower in the AHCM group and HTLVH group than in the normal control group,LSA decrease was more significant in the AHCM group as compared to the HTLVH group,while the HTLVH group was mainly characterized by a decrease in LSB,which was significantly lower as compared to the AHCM group (all P<0.05).Compared with the normal control group,the ABLR,AGLR,and ABMLR were significantly reduced in the AHCM group,while significantly increased in the HTLVH group (all P<0.05).The ROC curve showed that the AUC of ABLR,AGLR,ABMLR,and LSA was 0.873 to 0.916,using<1.28 as the cutoff value of ABLR,the sensitivity was 90.0％ and specificity was 88.7％ for diagnosing AHCM. Conclusions:The apical relative longitudinal strain indices can reflect the myocardial functional characteristics of AHCM patients,which are better than single apical longitudinal strain value.As the most representative indice,ABLR may be useful in distinguishing AHCM from left ventricular hypertrophy caused by other diseases,and can be used as a parameter for the evaluation of myocardial function damage in AHCM.