A Selectable Biomarker in Hair Follicle Cycles - Cathepsins: A Preliminary Study in Murine.

BACKGROUND/OBJECTIVE: Hair cycle is regulated by many biological factors. Cathepsins are involved in various physiological processes in human skin. Here, we investigated the cathepsin expression and distribution changes in follicular growth cycles for better understanding the hair cycles and to explore new intervention measures. METHODS: The 24 mice (C57BL/6, female, 7-week old) were selected and removed the back hair via rosin/paraffin method. At Day 8, Day 20, and Day 25, biopsy on post-plucking area was done. Immunohistochemical staining, Western blot, and Q-PCR were used to test the cathepsin B/D/L/E. RESULTS: In anagen, cathepsins (B, D, L, and E) were distributed in the hair follicle matrix, inner hair root sheath, and hair. In catagen, cathepsins were mainly observed in un-apoptosis inner root sheath and outer root sheath. Expression of cathepsins B-mRNA and L-mRNA was decreased from anagen and catagen to telogen. Cathepsin D-mRNA was increased in catagen and then decreased in telogen. Cathepsin E-mRNA was decreased in catagen and slightly increased in telogen. CONCLUSIONS: The distribution and expression of cathepsins B, D, L, and E in hair follicle changed with hair growth process which indicated that cathepsins might act as selectable biomarkers of hair cycle in different stages.

Dent disease manifesting as nephrotic syndrome.

Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the CLCN5 gene and OCRL gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis or nephrolithiasis, and progressive renal failure. Nephrotic syndrome is a glomerular disorder characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In this study, we report two cases of Dent disease manifesting as nephrotic syndrome. Two patients were initially diagnosed with nephrotic syndrome due to edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and responded to prednisone and tacrolimus therapy. Genetic testing revealed mutations in the OCRL and CLCN5 genes. They were eventually diagnosed with Dent disease. Nephrotic syndrome is a rare and insidious phenotype of Dent disease, and its pathogenesis is not fully understood. Patients with nephrotic syndrome are recommended to routinely undergo urinary protein classification and urinary calcium testing, especially those with frequently recurrent nephrotic syndrome and poor response to steroid and immunosuppressive therapy. To date, there is no effective drug treatment for Dent disease. About 30% to 80% of patients progress to end-stage renal disease at the age of 30-50.

Analysis and Prediction of Cross-Border e-Commerce Scale of China Based on the Machine Learning Model.

In the context of the rapid development of Internet technology, the integration of the world economy has been strengthened, and the continuous innovation of technology and foreign trade business forms has promoted the rapid development of cross-border e-commerce. Due to the lack of relevant data on cross-border logistics empirical research, this paper conducts a prediction study on the scale of China's cross-border e-commerce market based on machine learning models and combines the relevant financial reports of listed companies to determine the proportion of performance costs to turnover. Forecast of the scale of cross-border e-commerce in China. Combined with the total economic volume, industrial structure, domestic and foreign trade, online shopping development, people's life, and express development, the index system is established, and 11 indicators are initially established with reference to the selection principle of indicators. Combined with the research object, multiple regression and gray prediction methods are established. The relevant prediction model is tested, and the established model is tested to ensure the prediction accuracy. The forecast results show that by 2027, the size of China's cross-border e-commerce market will reach 30.8133 trillion yuan.

A retrospective study on the characteristics of renal pathological grades in HSPN children with mild to moderate proteinuria.

Objective: To investigate the characteristics of renal pathological grades in Henoch-Schönlein purpura nephritis (HSPN) children with mild to moderate proteinuria and the correlation between pathological grade and severity of proteinuria among this population. Methods: HSPN children who were presented with mild (150 mg <24 h urinary protein <25 mg/kg) to moderate (25 mg/kg ≤24 h urinary protein <50 mg/kg) proteinuria and performed renal biopsy without steroid ± immunosuppressant treatment in the Second Xiangya Hospital between January 2010 and March 2021 were involved. We retrospectively analyzed the correlation between age, disease course, degree of proteinuria, type of immunoglobulin deposits, C3 deposits in glomeruli and renal pathological grade. Results: (1) 72 HSPN children including 46 boys and 26 girls were included, with a mean age of onset of 9.01 ± 2.65 years old. The majority of these patients (62.5%) had a disease course between 1 week to 1 month. 51 patients presented with mild proteinuria and 21 patients with moderate proteinuria. (2) Renal biopsy results showed that ISKDC Grade IIIa were both predominant in mild proteinuria group (25, 49%) and moderate proteinuria group (11, 52.4%). 32 patients had grade II (44.4%), 2 had grade IIIb (2.8%), 1 had grade IV (1.4%), and 1 had grade VI (1.4%). There was no correlation between age, disease course and renal pathological grade (p > 0.05). (3) In patients with mild proteinuria (n = 51), 27 (52.9%) HSPN children had a pathological grade ≥ grade III. In patients with moderate proteinuria (n = 21), 13 (61.9%) HSPN children had grade ≥ III. There was no significant difference in the proportion of renal pathological grade between the 2 groups (p > 0.05). (4) There was no significant correlation between glomerular C3 deposits or immunoglobulin deposit types and renal pathological grade (p = 0.776 and p = 0.056 respectively). Conclusion: In HSPN children with mild to moderate proteinuria, longer disease course or heavier urinary protein level is not completely parallel with higher renal pathological grade. ISKDC grade IIIa is the most common pathological grade. Clinicians should pay great attention to the renal injury in patients with mild to moderate proteinuria.

Bartter-Like Syndrome as the Initial Presentation of Dent Disease 1: A Case Report.

Dent disease is a rare genetic disease characterized by low-molecular-weight proteinuria. Dent disease with Bartter-like syndrome is rare and can easily be misdiagnosed and mistreated. Herein, we report a case of Dent disease 1 with Bartter-like syndrome as the initial manifestation. The patient was admitted to The Second Xiangya Hospital of Central South University due to polydipsia, polyuria, and weakness of both lower limbs at 2 years of age. Laboratory tests showed that serum sodium, potassium and chlorine levels were low, while serum creatinine levels were normal. The calcium level in the urine was normal. The patient was initially diagnosed with Bartter syndrome, and despite medical interventions, he eventually developed chronic kidney disease stage 4 at 13 years of age. To determine the cause, the patient was recommended to undergo genetic testing, which showed a CLCN5 gene c. 941C > T mutation (p.S314L), and was finally diagnosed as Dent disease 1. The clinical manifestations of Dent disease are complex and diverse. For patients with atypical clinical manifestations or unsatisfactory therapeutic effects, genetic testing is recommended.

Transcriptome comparison of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients.

BACKGROUND: Oral isotretinoin is the first-line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear. AIMS: To compare the transcriptome profiles of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences. PATIENTS/METHODS: Peripheral blood of 43 patients with severe acne was collected before treatment. After 8-week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High-throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis. RESULTS: Ten acne patients (3 male and 7 female, age 31 ± 9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28 ± 7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin-effective and isotretinoin-ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T-cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long-term potentiation pathway, and FoxO signaling pathway. CONCLUSION: Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.

Transcriptome analysis of ultraviolet A-induced photoaging cells with deep sequencing.

Gene expression changes associate with many biological processes. However, the relative consequences of the genetic alterations induced by ultraviolet (UV)-A radiation on skin photoaging are still not clear. Here, we performed deep sequencing of the transcriptome and explored altered genes related to biological changes in repeated UV-A-irradiated human dermal fibroblasts (HDF) to better understand the skin photoaging mechanisms. The repeatedly UV-A-irradiated group (HDF were induced by 10 J/cm2 UV-A twice daily for 7 days) and the control group (HDF without irradiation) were evaluated. Expression genes profile was measured and compared using high-throughput sequencing on an Illumina HiSeq 2500 platform and DEGseq. Functional annotation and metabolic pathway analysis of genes with altered expression were preformed via National Center for Biotechnology Information, Uniprot, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Genes related to skin photoaging were verified by quantitative reverse transcription polymerase chain reaction. Transcriptome comparison revealed that 607 genes exhibited significant changes (P < 0.05), of which 238 genes were upregulated and 369 downregulated in UV-A-irradiated HDF. Functional annotations showed that genes altered by UV-A irradiation took part in a variety of biological process, cellular component synthesis, molecular function and metabolic pathway. Photoaging-related genes encoding elastin, sprout, cathepsin K, cathepsin D, cathepsin B ribose-phosphate diphosphokinase and phosphoglucomutase were identified to be changed. We obtained the comprehensive transcriptome and altered genes in repeated UV-A-irritated HDF and identified that the modulated genes were related to a wide panel of pathways and functions. Our results provide new insights into photoaging molecular mechanisms and suggest some novel targets for interfering in skin photoaging.