First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate.

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Circular RNA circ_0008934 promotes hepatocellular carcinoma growth and metastasis through modulating miR-1305/TMTC3 axis.

Circular RNAs (circRNAs) play important roles in the progression of hepatocellular carcinoma (HCC). However, the exact function of circ_0008934 in HCC is unknown. Our study aimed to investigate the expression characteristics of circ_0008934 in HCC and its effects on the proliferation and metastasis of HCC, and to explore the potential mechanism. In this study, circ_0008934 expression was found to be significantly upregulated in HCC tissues and cell lines by qRT-PCR. High level of circ_0008934 is closely associated with higher serum AFP (P < 0.001), larger tumor diameter (P = 0.012), microvascular invasion (P = 0.008) and poorer prognosis (P = 0.007) of HCC patients. Functionally, knockdown of circ_0008934 inhibited HCC cell proliferation, invasion and migration in vitro and vivo. Mechanically, circ_0008934 was a sponge of miR-1305 to facilitate the TMTC3 expression, and the TMTC3 expression in HCC tissues was negatively associated with the survival of HCC patients. Furthermore, rescued assays revealed that the circ_0008934 facilitated HCC proliferation, invasion and migration by regulating miR-1305/ TMTC3 signaling pathways. Overall, these results demonstrate that downregulation of circ_0008934 repress HCC growth and metastasis by upregulating miR-1305 to inhibit TMTC3, suggesting circ_0008934/ miR-1305/ TMTC3 regulatory axis may be a possible novel therapeutic target for HCC.

[Differential expression in ACE2, Ang(1-7) and Mas receptor during progression of liver fibrosis in a rat model].

OBJECTIVE: To investigate the changes in expression of the ACE2/Ang(1-7)/Mas receptor axis' components that occur during progression of liver fibrosis using a rat model system. METHODS: Thirty-six adult male Wistar rats, were randomly assigned to groups of normal control (n = 6; no manipulation) and liver fibrosis (n = 30; given a subcutaneous injection of 40% chronic carbon tetrachloride (CCl4)). At post-injection days 15, 30, 45, 60 and 75, 1 control rat and 6 modeled rats were sacrificed for analysis. Histopathological analysis of liver tissue was performed with hematoxylin-eosin and rapid Masson staining. Protein expression level of Ang(1-7) was determined by enzyme-linked immunosorbent assay, and of ACE2 and Mas receptor was evaluated by immunohistochemistry. Real-time PCR was used to measure the mRNA expression levels of ACE2 and Mas receptor. RESULTS: The expression levels of ACE2, Ang(1-7) and Mas receptor showed a statistically significant upward trend that followed the progression of fibrosis up to post-injection day 60 (P less than 0.01), but the significant increase was not seen from day 60 to day 75. CONCLUSION: Each component of the ACE2/Ang(1-7)/Mas receptor axis shows differential expression during the development of liver fibrosis and may contribute to disease progression.

[Studies on the chemical constituents from aerial parts of Gynura divaricata].

OBJECTIVE: To study the chemical constituents from aerial parts of Gynura divaricata. METHODS: The constituents were isolated on silica gel column chromatography, preparative TLC and Sephadex LH-20 column chromatography, identified by physicochemical properties and the structures were elucidated by spectral analysis. RESULTS: 10 compounds were isolated and identified as 2-(1', 2', 3', 4'-tetrahydroxybutyl)-6-(2", 3", 4"-trihydroxybutyl)-pyrazine (1), 2-(1', 2', 3', 4'-tetrahydroxybutyl)-5-(2", 3", 4"-trihydroxybutyl) -pyrazine (2), nicotinic acid (3), 5-hydroxy-picolinic acid(4), methyl-5-hydroxy-2- pyridinecarboxylate (5), adenosine (6), uridine (7), stigmasterol-5-O- beta-D-glucoside (8), dibutyl terephthalate (9), methyl chlorogenate (10). CONCLUSION: Compounds 1, 2, 5, 9, 10 are obtained from this genus for the first time, Compounds 3, 4 are obtained from this plant for the first time.

[Protecting effect of Chaenomeles speciosa broth on immunosuppressive mice induced by cyclophosphamide].

OBJECTIVE: To investigate the effects of Chaenomeles speciosa broth on immunoregulation for anti-tumor chemotherapy. METHODS: Immunosuppressive model was induced by cyclophosphamide (CTX) in mice. The mice were treated with the broth for 15 days. The serum hemolysin was observed in mouse sera. Spleen lymphocyte transformation and gene transcription related to the immunoregulation in spleen lymphocytes were detected. RESULTS: After administrated the broth, the serum hemolysin and lymphocyte transformation rates significantly increased and the mRNA expression of foxp3, TGF-beta, PD1, Fas, Bax were downregulated compared with CTX-group. CONCLUSION: Chaenomeles speciosa broth has protective effects on the immunosuppressive mouse induce by CTX.

A new cerebroside from Gynura divaricata.

A new cerebroside (1) was isolated from the aerial parts of Gynura divaricata DC., along with five known compounds: kaempferol (2), kaempferol 3-O-glucoside (3), kaempferol 3-O-rhamnosyl(1 --> 6)glucoside (4), beta-sitosteryl glucoside-6'-O-heptadecoicate (5) and 2-(1', 2', 3', 4'-tetrahydroxybutyl)-6-(2'', 3'', 4''-trihydroxybutyl)-pyrazine (6), which are isolated for the first time from this species. The structure of 1 was determined to be 1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 10Z)-2-[(2'R)-2'-hydroxylignocenoyl-amino]-10-octadecene-1,3,4-triol on the basis of chemical and spectroscopic evidence.

[Influence of interventional radiotherapy for severe postpartum hemorrhage on postpartum menorrhea].

OBJECTIVE: To discuss the influence of interventional radiotherapy for treating severe postpartum hemorrhage on postpartum menorrhea. METHODS: From Mar. 1995 to Feb. 2002, 18 cases of severe postpartum hemorrhage treated with arterial embolization served as the interventional group. Twenty parturients without postpartum complication were recruited as control group. The continuance of lochia, recovery of menorrhea between the two groups were compared. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)) of the non-lactating women in the two groups were assayed during the 3rd-5th days of the first menstrual cycle. RESULTS: Continuance times of lochia were (33.9 +/- 2.0) days, and (36.2 +/- 3.1) days in interventional group and control group, respectively. Recovery times of menorrhea were (75 +/- 17) days, and (95 +/- 16) days in interventional group and control group. The quantity of the postpartum menorrhea was 1.3 +/- 0.1 times of that before delivery in interventional group, 1.3 +/- 0.2 times of that in control group. The number of menstrual cycle before recovery to normal menorrhea was 2 cycles in interventional group, 1.9 cycles in control group. Postpartum menstrual cycle was (33.9 +/- 2.2) days in interventional group, (33.2 +/- 1.6) days in control group. Serum FSH, LH, E(2) of the non-lactating women during the 3rd approximately 5th days of the first menstrual cycle were (5.2 +/- 1.1) U/L, (7.5 +/- 1.6) U/L, (262 +/- 14) pmol/L in interventional group, (4.3 +/- 2.1) U/L, (6.3 +/- 1.3) U/L, (280 +/- 12) pmol/L in control group. There was no significant difference between the two groups (P > 0.05). CONCLUSIONS: No obvious influence of interventional radiotherapy for postpartum hemorrhage on postpartum menorrhea was observed.