Association between hypertensive disorders of pregnancy and gestational diabetes and risk of atopic dermatitis in childhood: A systematic review and meta-analysis.

The purpose of this review was to examine if maternal hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) result in an increased risk of atopic dermatitis or eczema (AD-E) in childhood. We searched the databases of PubMed, Embase, CENTRAL, Web of Science, and Scopus for cohort or case-control studies up to 25th June 2023. Random-effects meta-analysis was done to generate the odds ratio (OR) of the association between HDP/GDM and AD-E. Eight studies were included. Meta-analysis of five studies showed that GDM in the mother was associated with an increased risk of AD-E in the offspring (OR: 1.35 95% CI: 1.13, 1.61 I2 = 61%). Pooled analysis of four studies demonstrated no association between HDP and risk of AD-E in the offspring (OR: 1.03 95% CI: 0.99, 1.08 I2 = 0%). The results did not change on sensitivity analysis and subgroup analysis based on study type, method of AD-E diagnosis, and sample size. This meta-analysis suggests that GDM may significantly increase the risk of AD-E in childhood, however, HDP does not seem to impact the risk of AD-E. Evidence is limited by the small number of studies and high interstudy heterogeneity. Further studies are needed to improve the quality of evidence.

Detection of invasive Candida albicans infection using a specific (99m)Tc-labeled monoclonal antibody for the C. albicans germ tube.

Accurate diagnosis is critical for effective treatment of the invasive infection by Candida albicans. Here, we investigated whether a (99m) technetium (Tc)-labeled Fab' fragment of the monoclonal antibody specific for the C. albicans germ tube could specifically identify an invasive C. albicans infection. The germ tube of C. albicans was used as an immunogen to obtain monoclonal antibodies and the Fab' fragment of MAb03.2 C1-C2 with highest affinity and specificity was labeled with (99m)Tc. In vitro binding assays showed that the labeled Fab' preferentially bound to the germ tubes of C. albicans (4.23 ± 0.17 × 10(2) Bq per 1 × 10(7) cells). These values were significantly higher than those for blastospores of C. albicans, blastospores of heat-killed C. albicans, Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli (P < 0.05). By using in vivo biodistribution and planar imaging with single photon emission computed tomography, we demonstrated a significant specific accumulation of radioactivity in C. albicans-infected tissues. In summary, (99m)Tc-MAb03.2 C1-C2 Fab' is able to specifically accumulate in C. albicans-infected tissues, but not in tissue infected with A. fumigatus or bacteria or in a sterile inflammation. This study provides a new and specific radiopharmaceutical for the diagnosis of invasive C. albicans infections.

An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.

Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs - rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis.

Interrupted time series analysis for the impact of integrated medical insurance on direct hospitalization expense of catastrophic illness.

In 2016, China initiated the merge of the urban resident basic medical insurance scheme and new rural cooperative medical scheme into one unified health insurance scheme: the urban and rural resident basic medical insurance. This study investigates the impact of integrated insurance on the direct hospitalization cost of inpatients with catastrophic illnesses. An interrupted time series analysis was conducted based on a sample of 6174 inpatients with catastrophic illness from January 2014 to December 2018. The factors surveyed included per capita total inpatient expense, out-of-pocket expense, and reimbursement ratio. Univariate analysis indicated that after the implementation of the unified urban and rural medical insurance, the reimbursed expense increased from 9398 to 13,842 Yuan (P < 0.001), average reimbursement ratio increased from 0.57 to 0.59 (P < 0.05). Expenses on both western and traditional medicines increased, although the proportion of medicine expense decreased after the integration. Interrupted time series analysis showed that per capita total inpatient expense and per capita out-of-pocket expense increased but showed a gradually decreasing trend after the integration. After the integration of urban and rural medical insurance, the average reimbursement ratio increased slightly, which had limited effect on the alleviation of patients' financial burden. Furthermore, the integration effect on inpatient expense is offset by increased out-of-pocket medical expense due to suspected supplier-induced demand.

Study of the biological function and penetration pathways of the mouse epidermal growth factor ethosomal delivery system.

Biological agents are becoming increasingly popular for therapeutic applications in epidermal diseases. Ethosomes facilitate the transdermal/topical delivery of biological macromolecules. The mouse epidermal growth factor (mEGF) was selected as the model biological agent. The aim of this experiment was to determine the penetration pathways and biological functions of the mEGF ethosomal delivery system after its topical application. The mEGF ethosomal delivery system was topically applied on the dorsal skin of C57BL/6 mice at different time points. Freshly excised skin samples were obtained by skin biopsies and shock-frozen, and immunofluorescence was performed. The results showed that penetration of mEGF ethosomes was mainly through the pilosebaceous unit and partly through the intercellular domain. Biological agents encapsulated in the ethosomal delivery system could reach each site of the pilosebaceous unit. We also found that mEGF ethosomes had caused successful transition of the hair follicles from the telogen to the anagen phase of the hair cycle.

The association of genetic variants in chemokine genes with the risk of psoriasis vulgaris in Chinese population: A case-control study.

This study aimed to investigate the influence of polymorphisms in chemokine genes, including MCP1, CCR2, and CCR5 with psoriasis vulgaris (PV) risk in a Chinese population.The genotyping of studied polymorphisms through polymerase chain reaction (PCR) and sequencing was conducted in 142 PV patients and 147 healthy controls. The genotype distribution of the polymorphisms in the control group was checked to determine whether it conformed to Hardy-Weinberg equilibrium (HWE). The genotype and allele frequencies were compared between PV patients and the healthy controls using Chi-square test. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the relative risk of PV related to genetic variants.CCR2 rs1799864 polymorphism was associated with significantly elevated risk of PV (AA+AG vs GG: OR = 1.62, 95% CI = 1.02-2.59; A vs G: OR = 1.48, 95% CI = 1.02-2.16). In the meanwhile, CCR5 rs1800024 polymorphism also exhibited significant differences in genotype and allele distribution (P < .05), demonstrating its promoting effect on the risk of PV under heterozygous model (OR = 1.73, 95% CI = 1.06-2.82), dominance model (OR = 1.83, 95% CI = 1.14-2.94), and allele model (OR = 1.68, 95% CI = 1.13-2.48).CCR2 rs1799864 and CCR5 rs1800024 polymorphisms may function as independent risk factors for PV in Chinese population.

Low-expression of miR-7 promotes cell proliferation and exhibits prognostic value in osteosarcoma patients.

AIM: MicroRNAs (miRNAs) play important roles in occurrence and development of osteosarcoma. Previous studies had verified the role of microRNA-7 (miR-7) in various diseases, especially in cancers. Our purpose in this study was to investigate the values of miR-7 in development and prognosis of osteosarcoma. METHODS: QRT-PCR was used to measure the expression of miR-7 in osteosarcoma tissues, adjacent tissues and healthy tissues as well as in osteosarcoma cell lines MG63, U2OS and normal osteoblastic cell line hFOB1.19. CCK-8 and siRNA assays were performed to estimate the effect of miR-7 in the process of cell proliferation. The Kaplan-Meier and Cox regression analysis were performed to detect the prognostic values of the miR-7 in osteosarcoma patients. RESULTS: The results demonstrated that miR-7 expression decreased in osteosarcoma tissues and cell lines compared with the controls. Proliferation assay declared that the cell proliferation was accelerated by down-regulation of miR-7. Kaplan-Meier exhibited that the overall survival time of low-miR-7 expression was shorter than those with high-miR-7 expression (P=0.001). Cox regression analysis revealed that Enneking, distant metastasis and recurrence were all prognostic factors just like low-miR-7. CONCLUSION: The expression of miR-7 was lower in osteosarcoma tissues and cell lines and miR-7 acted as a tumor suppressor. The low-expression of miR-7 was associated with clinicopathologic characteristics (age, tumor site, Enneking, therapies). Moreover, miR-7 might be an independent prognostic marker and promote cell proliferation in osteosarcoma.

Bidirectional immunoregulation of calcineurin inhibitor tacrolimus on FOXP3 transcription?

The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.

[Prepare and study on the characterization of a new monoclonal antibody to germ tube Candida albicans].

AIM: To prepare and identify the monoclonal antibody(mAb) specific for the germ tube of Candida albicans. METHODS: mAb were prepared via hybridoma technique. Indirect immunofluorescence (IIF) was used to analyze the activity and specificity of the mAb. The protection of the mAb was analyzed via the inhibition of the mAb to the germ tube formation and the adhesion of C.albicans to the epithelial and endothelial cells. The frozen hybridoma cells were cultured to analyze the ability of the secretion of the mAb. RESULTS: mAb03.2C1-C2 belongs to IgG1 subclass. Relative molecular mass (M(r)) of antigens recognized by the mAb was 156, 48, 22 and 12. The target antigen could be detected 30 minutes after the germ tube formation. The epitope might lie in the N-carbohydrate chain. mAb03.2C1-C2 was shown by IIF test to be specific to the surface of the germ tube or mycelium phase of C.albicans. In the protective mAb screening experiment, it was found that mAb3.2C1-C2 could inhibit C.albicans germ tube formation and the adhension of C.albicans to the epithelial and endothelial cells. CONCLUSION: In vitro, mAb03.2C1-C2 could inhibit the formation of germ tube of C.albicans, which could depress the invasiveness of C.albicans. This anti-C.albicans cell wall surface-specific mAb may be a good candidate for use in tests for the rapid differentiation of the two closely related species C.albicans and C.dubliniensis.