[UGT1A1 gene mutation spectrum with indirect hyperbilirubinemia in children].

Objective: To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Methods: Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Results: Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G > A accounted for 37.5% (6/16), c.1456T > G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin (t = 5.539, P < 0.05), and indirect bilirubin (t = 5.312, P < 0.05). However, there was no significant difference in direct bilirubin levels (t = 1.223, P > 0.05) and age of onset (t = 0.3611, P > 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T > G homozygous mutations had the highest serum bilirubin levels. Conclusion: The common pathogenic variants of the UGT1A1 gene sequence are c.1456T > G, c.211G > A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

9-Cis-retinoic acid exhibits antifibrotic activity via the induction of cyclooxygenase-2 expression and prostaglandin E2 production in scleroderma fibroblasts.

BACKGROUND: The pathogenesis of scleroderma (SSc) is not fully understood, and there is no effective treatment for this chronic disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit antifibrotic activity and improve the clinical symptoms of patients with SSc. However, the mechanisms by which RA elicits its antifibrotic actions remain to be determined. OBJECTIVE: To elucidate the underlying mechanisms by which retinoids exert beneficial effects on SSc. METHODS: Cultured skin fibroblasts from patients with SSc were treated with retinoids (9-cis-, 13-cis- and all-trans-retinoic acid) and their effect on the expression of cyclooxygenase (COX)-2, connective tissue growth factor (CTGF) and type I and III collagen and on the production of PGE(2) was examined. COX-2 expression was analysed by western immunoblotting, PGE(2) production by enzyme immunoassay and CTGF expression, and type I and III collagen expression by reverse transcriptase PCR and western immunoblotting. RESULTS: In cultured SSc fibroblasts, 9-cis-RA significantly increased COX-2 protein expression and PGE(2) production and inhibited the expression of CTGF and type I and III collagen. We further found that expression of CTGF and of type I and III collagen mRNA was inhibited by exogenous PGE(2) in SSc fibroblasts. CONCLUSION: In vitro, 9-cis-RA induced COX-2 expression and PGE(2) production in SSc fibroblasts and PGE(2) downregulated CTGF expression, leading to the inhibition of type I and III collagen synthesis. Our results indicate that the clinical effects of 9-cis-RA on SSc are, at least in part, attributable to the induction of PGE(2) and the subsequent suppression of CTGF expression that results in the blockade of collagenogenesis.

Newly identified respiratory viruses associated with acute lower respiratory tract infections in children in Lanzou, China, from 2006 to 2009.

Nasopharyngeal aspirates were collected from 813 children ≤ 14 years old with acute lower respiratory tract infections in Lanzhou, China, from December 2006 to November 2009. PCR or RT-PCR was used to screen for the presence of 10 respiratory viruses. Viral agents were identified in 73.92% (601/813) of specimens, including RSV in 40.71%, hMPV in 6.15%, IFVA in 7.13%, IFVB in 0.98%, PIV1-3 in 7.87%, HCoV-HKU1 in 2.21%, HCoV-NL63 in 3.81%, HRV in 19.93%, AdV in 7.50% and HBoV in 11.56%. Two or more viruses were detected in 34.44% (280/813) of cases. The newly identified respiratory viruses, HBoV, hMPV, HCoV-HKU1 and HCoV-NL63, accounted for 22.01% of the detected viral pathogens. RSV and HRV were frequently detected in patients with bronchiolitis, and hMPV was frequently associated with pneumonia. HCoV-NL63 was found to be one of the causative agents of acute respiratory wheezing in young children. No seasonal variation was found in the incidence of detection of HCoV-HKU1, HCoV-NL63 or HBoV. This 3-year study demonstrated that viral pathogens play an important role in children with ALRTIs, and more attention should be paid to these newly identified viral agents.

Childhood psoriasis: a study of 277 patients from China.

OBJECTIVES: Psoriasis is common in childhood. The aim of this study was to present the clinical and epidemiological profile of childhood psoriasis in China. METHODS: A total of 277 childhood psoriasis patients younger than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, spss 10.0 and Falconer's method. RESULTS: The median age was 11 years. The male : female ratio was 1:1.13. The median age of onset was 10 years. Of the patients, 48.7% had previous episodes of psoriasis. Of the 277 children with psoriasis, 68.6% had plaque-type psoriasis, 28.9% had guttate psoriasis, 1.1% presented pustular forms of psoriasis and 1.4% had erythroderma. The extensor surface of the extremities was the most frequently affected site in our patients, followed by the appearance of lesions on the scalp. A positive family history of psoriasis was found in 34.3% patients. The prevalence of psoriasis in first- and second-degree relatives was 7.0% and 1.0%, respectively. The heritability of psoriasis in first- and second-degree relatives was 72.67% and 55.18%, respectively. CONCLUSION: Our epidemiologic studies offer the information about Han Chinese distribution, which provide clues to describe psoriasis in children.

Effect of small interfering RNA on the expression of connective tissue growth factor and type I and III collagen in skin fibroblasts of patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is characterized by an excessive production of extracellular matrix. It is widely accepted that fibrosis is induced by transforming growth factor (TGF)-beta in the early stage and is subsequently maintained by connective tissue growth factor (CTGF). CTGF is a cysteine-rich mitogenic peptide that has been involved in various fibrotic disorders and can be induced in fibroblasts by activation with TGF-beta. OBJECTIVES: To evaluate the effect of small interfering RNA (siRNA) targeting CTGF on the expression of CTGF and type I and type III collagen in SSc. METHODS: Skin fibroblasts from patients with SSc were cultured in vitro and later transfected using four CTGF-specific siRNAs and one nonspecific siRNA. The effect of CTGF-specific siRNAs on the expression of CTGF and type I and type III collagen was examined and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry. RESULTS: Semiquantitative RT-PCR analysis showed that the four CTGF-specific siRNAs significantly reduced CTGF mRNA expression (P < 0.001), of which siRNA742 showed the strongest inhibitory effect with an inhibitory rate of 73%. Three of the four siRNAs could also depress the transcriptional levels of type I and type III collagen mRNA (P < 0.001), of which siRNA742 showed the strongest inhibitory effect with an inhibitory rate of 37% and 29% for type I and type III collagen, respectively. Western blot analysis further demonstrated that three CTGF-specific siRNAs could significantly decrease CTGF protein level (P < 0.001). In addition, immunocytochemical analysis showed that the expression of type I collagen was significantly decreased in fibroblasts after transfection with siRNA742, whereas inhibition of expression of type III collagen was modest. CONCLUSIONS: Our data for the first time showed that CTGF RNA interference could inhibit expression of CTGF and type I and III collagen in SSc fibroblasts and indicated that CTGF might be an upstream factor regulating type I and type III collagen synthesis, particularly type I collagen. Our findings suggest that silencing CTGF expression might facilitate a potential therapeutic approach for SSc.

The effect of mizolastine on expression of vascular endothelial cell growth factor, tumour necrosis factor-alpha and keratinocyte-derived chemokine in murine mast cells, compared with dexamethasone and loratadine.

It has been shown that many antihistamines may have anti-inflammatory activity in addition to being H1 antagonists. Mizolastine (MIZ), a novel antihistamine, might also have anti-angiogenesis properties. In this study, we investigated the influence of MIZ on proangiogenesis factors, vascular endothelial cell growth factor (VEGF), tumour necrosis factor (TNF)-alpha and keratinocyte-derived chemokine (KC) in murine mast cells by using ELISA and RT-PCR, as compared with dexamethasone (DEX) and loratadine (LOR). Our results show that MIZ is effective in the inhibition of KC, VEGF and TNF-alpha release induced by an IgE-dependent mechanism, in a time- and dose-dependent manner. The differences between the inhibitory effects of the three drugs on these proangiogenic factors were rather subtle. Semiquantitative analysis using RT-PCR showed that the three drugs significantly reduced VEGF165, VEGF120, TNF-alpha and KC mRNA expression. Statistical results revealed that the effect of DEX on VEGF165 mRNA was different from that of MIZ or LOR (P < 0.01) and the differences between the three drugs on VEGF120, TNF-alpha and KC mRNA were not statistically significant (P > 0.05). These findings raise the possibility that MIZ can mediate anti-angiogenesis activity and that the effect may depend not only on the inhibition on the levels of cytokine proteins but also at the mRNA level.

Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31.

BACKGROUND: Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13-8q24.21 and 15q22-15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four-generation Chinese family with punctate PPK. METHODS: Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and the haplotype was constructed using Cyrillic version 2.02 software. RESULTS: We failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point LOD score of 5.38 at D15S153 (theta = 0.00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06 cM with the previously reported punctate PPK region. CONCLUSIONS: This study refines a disease gene causing punctate PPK to a 5.06-cM interval at 15q22.2-15q22.31.

[A tentative discussion on the aim of Socialist population production].

PIP: The general goals of a Socialist population policy are first discussed. The author examines possible conflicts between society's needs in China and the wishes of individual families concerning the number of children they would like to have. The need to provide old-age security and to improve the quality of a smaller population through education is stressed.^ieng

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two-point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores < - 2) at Theta = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.

A novel mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. It is caused by mutations of the RNA-specific adenosine deaminase gene. We report the identification of a Chinese family with a three-generation pedigree of DSH, in whom a novel tyrosine substitution mutation in DSRAD was demonstrated: a heterozygous nucleotide A-->G transition at position 2879 in exon 10 of the DSRAD gene was detected.

Refinement of a locus for Marie Unna hereditary hypotrichosis to a 1.1-cM interval at 8p21.3.

BACKGROUND: Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal congenital alopecia with progressive hair loss starting in early childhood and accelerating at puberty. A locus for MUHH has been mapped on chromosome 8p21 but no genes for MUHH have been identified to date. OBJECTIVES: To refine the MUHH locus to a narrow chromosome region to facilitate cloning of the gene. METHODS: We performed genotyping and linkage analysis in a multigeneration Chinese family with MUHH, using 18 high-density microsatellite markers spanning the previously mapped interval at 8p21. RESULTS: Significant evidence for linkage was observed in this region, with a maximum two-point LOD score of 3.01 (theta = 0). Haplotype analysis localized the MUHH locus within the region defined by D8S282 and D8S1839. This region overlaps by 1.1-cM with the previously reported MUHH region and represents a physical distance of about 380 kb. CONCLUSIONS: This study provides a refined map location (1.1 cM) for isolation of the gene causing MUHH. These data also indicate the existence of a common MUHH locus at 8p21.3 between affected caucasian and Chinese families.