[Clinical characteristics and genetic analysis of a Chinese pedigree affected with Alström syndrome].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a Chinese pedigree affected with Alström syndrome. METHODS: A pedigree with 5 members affected with Alström syndrome who had visited the First Affiliated Hospital of Zhengzhou University in February 2021 was selected as the study subject. Clinical data of the pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA. Genetic testing was carried out for the eldest daughter and third son through whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The eldest daughter (14 years old) and the third son (11 years old) both had congenital nystagmus, amblyopia, growth retardation and type 2 diabetes. WES revealed that both had harbored homozygous c.3538A>T (p.Lys1180*) variant of the ALMS1 gene. Sanger sequencing confirmed that the father, mother, and second daughter were all heterozygous carriers. Based on the Guidelines for Genetic Variation and the Technical Standards for Interpretation and Reporting of Primary Copy Number Variations, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The homozygous c.3538A>T (p.Lys1180*) variant of the ALSM1 gene probably underlay the Alström syndrome in this pedigree, which has provided a reference for the clinical treatment.

Case report: a Chinese girl like atypical Rubinstein-Taybi syndrome caused by a novel heterozygous mutation of the EP300 gene.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is an extremely rare autosomal dominant inheritable disorder caused by CREBBP and EP300 mutations, while atypical RSTS harbouring variant from the same genes but not obvious resembling RSTS. There are only a few cases of Menke-Hennekam syndrome (MKHK) with variant of exon 30 or 31 of CREBBP or EP300 gene have been reported that not resembling RSTS recent years. Atypical RSTS cannot be accurately classified as MKHK, nor is it easy to identify the obvious classic characteristics of RSTS. The clinical manifestations and genetic variation of atypical RSTS are not fully understood. CASE PRESENTATION: We present a Chinese core family with a girl had recurrent respiratory tract infection and developmental delay. The patient with language and motor mild development retardation, she has slight abnormal facial features, mild hirsutism and post-axial hexadactylia of left foot. Her cisterna magna is enlarged to connect with the fourth ventricle, and the ventricular system is enlarged. She has a malacia beside the posterior horn of the left lateral ventricle. The patient has primary low immunoglobulin G and A, but her level of immunoglobulin M content in blood is normal. The patient harbors a novel heterozygous frameshift variant of c.2499dupG in exon 14 of EP300 gene, that it is proved to de novo origin. The mutation is judged to be a pathogenic mutation, and it has high-grade pathogenic evidence. CONCLUSION: The clinical and genetic evaluation of this case corroborates that clinical features caused by c.2499dupG in exon 14 of EP300 are less marked than RSTS2 patient although it is difficult to establish an accurate genotype-phenotype correlation. Our additional case also helps to deepen the clinical and genetic spectrum in this disorder. The case provides a novel mutation of EP300 and enriches the phenotypes related with the gene. We have contributed new variation and disease information for guardians and doctors to broaden the knowledge about EP300-RSTS genotype and phenotype, this may contribute to ameliorate the health management of patients and improve the genetic counseling to the families.

[Risk factors for recurrence after intravitreal anti-vascular endothelial growth factor injection for retinopathy of prematurity]. / çŽ»ç’ƒä½“è ”å† æ³¨å°„æŠ—è¡€ç®¡å† çš®ç”Ÿé•¿å› å­æ²»ç–—æ—©äº§å„¿è§†ç½‘è†œç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS: Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.

Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells.

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 µM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.

Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice.

Alismatis rhizoma (AR), which is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae), is an important component of many famous Chinese formulas for hypoglycemic. This study aimed to evaluate the insulin resistance (IR) alleviating effects of AR triterpenes (ART) and ART component compatibility (ARTC, the mixture of 16-oxo-alisol A, 16-oxo-alisol A 23-acetate, 16-oxo-alisol A 24-acetate, alisol C, alisol C 23-acetate, alisol L, alisol A, alisol A 23-acetate, alisol A 24-acetate, alisol L 23-acetate, alisol B, alisol B 23-acetate, 11-deoxy-alisol B and 11-deoxy-alisol B 23-acetate) in high-fat diet-induced IR mice and plamitate-treated IR C2C12 cells, respectively. A dose of 200 mg/kg of ART was orally administered to IR mice, and different doses (25, 50, and 100 µg/ml) of ARTC groups were treated to IR C2C12 cells. IPGTT, IPITT, body weight, Hb1AC, FFA, TNF-α, MCP-1, and IR-associated gene expression (p-AMPK, p-IRS-1, PI3K, p-AKT, p-JNK, and GLUT4) were measured in IR mice. Glucose uptake, TNF-α, MCP-1, and IR-associated gene expression were also measured in IR C2C12 cells. Results showed that ART alleviated high-fat diet-induced IR in the skeletal muscle of mice, and this finding was further validated by ARTC. This study demonstrated that ART presented a notable IR alleviating effect by regulating IR-associated gene expression, and triterpenes were the material basis for the IR alleviating activity of AR.

Anti-osteoporotic effects of alisol C 23-acetate via osteoclastogenesis inhibition.

Alismatis rhizoma (AR) is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae). This traditional Chinese formula is diuretic, hypoglycemic, and hypolipidemic. Alisol C 23-acetate (AC23A) from AR is anti-inflammatory and ameliorates certain metabolic diseases. However, the mechanism by which AC23A mitigates osteoporosis is unknown. The present study investigated the anti-osteoporotic effects of AC23A in vivo and in vitro. In an ovariectomized (OVX) rat model, AC23A ameliorated OVX-induced organ coefficients and trabecular bone loss. In OVX rats, AC23A treatment lowered serum TRAP5b, CTK, ß-CTX, TNF-α, IL-6, and IL-1ß, raised serum E2, and did not significantly change serum OCN or BALP. AC23A inhibited osteoclast formation in a rat co-culture system without affecting osteoblast activity. RANK (receptor activator of nuclear factor kappaB) signaling channels are vital osteoclastogenesis transcription elements. AC23A inhibited RANK ligand (RANKL)-induced TRAP, c-Fos, MMP9, NFATc1, and CTK expression and JNK phosphorylation. Therefore, AC23A is anti-osteoclastogenic in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Moreover, AC23A could help prevent or limit osteoclast-mediated bone diseases by inhibiting osteoclastogenesis.