Xing-Xing Zhang

Vissers‐Bodmer Syndrome (VIBOS) is an autosomal dominant disorder caused by variants in the CNOT1 gene. It is characterized by systemic developmental and language‐motor delay, intellectual disabilities, growth and behavioral abnormalities, hypotonia, and distal skeletal defects, such as deformities of the hands and feet. This syndrome becomes evident during infancy and can display a highly variable phenotype. Thirty‐nine individuals with heterozygous de novo CNOT1 variants were first reported in 2019. Herein, we report a child with VIBOS who exhibited delayed motor development for over 4 years, along with hypotonia and atypical facial features. Notably, the patient developed short stature as the primary characteristic without any intellectual disability or organic nervous system lesions. Genetic testing revealed a de novo base duplication variant in exon 5 of the CNOT1 gene, NM_016284.5( CNOT1 ):c.316_317dup(p.Pro107Serfs*10). Importantly, the pathogenicity of this specific variant has not been reported in relevant literature. This study reports a new variant, thereby enriching the variant spectrum of CNOT1 associated with VIBOS, and contributes to the genetic counseling of affected families.

Background: To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes.Methods: A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated via meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model.Results: Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by −0.21% (95% CI, −0.33 to −0.10), weight by −4.04 kg (−4.8 to −3.27), systolic pressure by −2.57 mmHg (−4.11 to −1.03), and diastolic blood pressure by −1.02 mmHg (−1.99 to −0.06). In addition, there was a decrease in prandial insulin dose (WMD, −4.23 IU; 95% CI, −5.26 to −3.20), basal insulin dose (−2.40 IU; −3.93 to −0.87), and total insulin dose (−5.73 IU; −10.61 to −0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33–3.77).Conclusion: Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events.Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

探讨儿童腺病毒肺炎并发噬血细胞综合征(HLH)的临床特征。 回顾性分析2019年3~9月7例腺病毒肺炎并发HLH患儿的临床资料。 患儿年龄11个月至5岁，其中2岁以下5例，男性5例，均无基础疾病。患儿均以持续高热伴咳嗽住院，热峰在39~41℃之间。随着疾病进展，出现肝大7例，脾大6例。血常规两系或三系减少，伴血清铁蛋白(SF)、C反应蛋白(CRP)、降钙素原(PCT)、乳酸脱氢酶(LDH)升高。吞噬血细胞现象6例。肺部影像学提示肺炎改变。7例均经病原学宏基因检测鉴定为人腺病毒7型感染，同时HLH基因检测无异常，确诊为继发性HLH。7例均采用人免疫球蛋白治疗，地塞米松+依托泊苷化疗4例，单用地塞米松3例，血浆置换4例。死亡2例，好转出院5例。与5例存活患儿相比，2例死亡病例血常规中三系降低更明显，CRP、PCT、SF、LDH升高更明显。 腺病毒肺炎并发HLH的主要临床特征为持续高热，外周血出现进行性两系或三系降低及肝脾肿大等其他器官系统受累。CRP、PCT、SF、LDH显著升高可能提示预后不良。

该文报道一例Ⅰ级POU结构域转录因子1（POU1F1）基因变异导致的联合垂体激素缺乏症Ⅰ型（CPHD1）的临床及遗传学特征。患儿女，2岁3个月，主要表现为身材矮小、前额突出、眼球内陷、下颌短小、皮肤松弛、中枢性甲状腺功能减退、完全性生长激素缺乏、垂体前叶发育不良。经基因分析发现POU1F1基因存在新杂合变异c.889C > T（p.R297W），父母该位点为野生型，根据美国医学遗传学与基因组学学会指南分析该变异为可能致病性变异，既往未见文献报道，符合常染色体显性遗传。该患儿确诊为CPHD1。经生长激素及左甲状腺素钠片联合治疗1年后，身高增长19.8 cm，呈追赶性生长趋势。该研究丰富了POU1F1基因的突变谱，对联合垂体激素缺乏的诊断与分型有重要意义。

Background: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by CYP19A1 overexpression. Clinical manifestations of AEXS include pre- or peri-pubertal gynecomastia, advanced bone age and compromised adult height. Case presentation: Here we report an 8-year-old boy diagnosed with AEXS by chromosomal array that revealed a 1.1 Mb novel de novo duplication at 15q21.2, with a predicted final height of 157.4 cm. We prescribed letrozole and growth hormone (GH) to maximize his linear growth. Without further bone age advancement, his height increased from 137.7 cm to 144 cm after an 8-month treatment period. Conclusions: We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.