Inadequate linear catch-up growth in children born small for gestational age: Influencing factors and underlying mechanisms.

A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.

FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

The Spliceosome Factor EFTUD2 Promotes IFN Anti-HBV Effect through mRNA Splicing.

Methods: Using a CRISPR/Cas9 gene-editing system, EFTUD2 single allele knockout HepG2.2.15 cells were constructed. Subsequently, the HBV biomarkers in EFTUD2+/- HepG2.2.15 cells and wild-type (WT) cells with or without IFN-α treatment were detected. And the EFTUD2-regulated genes were then identified using mRNA sequence. Selected gene mRNA variants and their proteins were examined by qRT-PCR and Western blotting. To confirm the effects of EFTUD2 on HBV replication and IFN-stimulated gene (ISG) expression, a rescue experiment in EFTUD2+/- HepG2.2.15 cells was performed by EFTUD2 overexpression. Results: IFN-induced anti-HBV activity was found to be restricted in EFTUD2+/- HepG2.2.15 cells. The mRNA sequence showed that EFTUD2 could regulate classical IFN and virus response genes. Mechanistically, EFTUD2 single allele knockout decreased the expression of ISG-encoded proteins, comprising Mx1, OAS1, and PKR (EIF2AK2), through mediated gene splicing. However, EFTUD2 did not affect the expression of Jak-STAT pathway genes. Furthermore, EFTUD2 overexpression could restore the attenuation of IFN anti-HBV activity and the reduction of ISG resulting from EFTUD2 single allele knockout. Conclusion: EFTUD2, the spliceosome factor, is not IFN-inducible but is an IFN effector gene. EFTUD2 mediates IFN anti-HBV effect through regulation of gene splicing for certain ISGs, including Mx1, OAS1, and PKR. EFTUD2 does not affect IFN receptors or canonical signal transduction components. Therefore, it can be concluded that EFTUD2 regulates ISGs using a novel, nonclassical mechanism.

Association of Elongation Factor Tu GTP-binding Domain-containing 2 Gene (EFTUD2) Polymorphism with the Risk of Hepatitis B Virus Infection.

BACKGROUND: The elongation factor Tu GTP-binding domain-containing 2 gene (EFTUD2) participates in antiviral immune responses. However, the association between genetic polymorphisms of EFTUD2 and hepatitis B virus (HBV) infection susceptibility has not been well-studied. We analyzed the relationship between single nucleotide polymorphisms (SNPs) of EFTUD2 and HBV infection susceptibility and clarified the potential function. METHODS: In total, 448 control subjects and 379 patients with chronic HBV infection from Zhangjiagang First People's Hospital (Jiangsu, China) were enrolled. Sequenom iPLEX assay was used to detect genotypes of four SNPs (rs1071682, rs2277617, rs2289674, and rs3809756). Dual-luciferase reporter vectors with wild-type A and mutant-type C alleles of EFTUD2 rs3809756 were transfected into HepG2 cells to explore effects on transcription activity. RESULTS: Only rs3809756 was significantly associated with HBV infection susceptibility (P < .05). The risk of HBV infection was higher in individuals carrying the rs3809756-CC genotype than in those carrying the rs3809756-AA genotype (odds ratio [OR] = 1.945, 95% confidence interval [CI] = 1.129-3.351, P = .017). Subgroup analysis based on the dominant model revealed that rs3809756-AC and rs3809756-CC carriers had a significantly higher risk of HBV infection than rs3809756-AA carriers among patients who were male (OR = 1.732, 95% CI = 1.218-2.464, P = .002), were aged ≥47 years (OR = 1.502, 95% CI = 1.050-2.148, P = .026), or without liver cirrhosis (OR = 1.407, 95% CI = 1.077-1.838, P = .012). In the dual-luciferase reporter assay, the relative luciferase activity of rs3809756-C was significantly lower than that of rs3809756-A (P < .05). CONCLUSION: EFTUD2 rs3809756A>C was associated with HBV infection susceptibility and might be involved in the downregulation of promoter activity.

Advances in HBV infection and replication systems in vitro.

BACKGROUND: Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently closed circular DNA (cccDNA) in host cells after HBV infection, current antiviral drugs cannot eradicate HBV. Therefore, the development of an active cell culture system supporting HBV infection has become the key to studying HBV and developing effective therapeutic drugs. MAIN BODY: This review summarizes the significant research achievements in HBV cell culture systems in vitro, including embryonic hepatocytes and primary hepatocytes, which support the virus infection process most similar to that in the body and various liver tumor cells. The discovery of the bile-acid pump sodium-taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has advanced our understanding of HBV biology. Subsequently, various liver cancer cells overexpressing NTCP that support HBV infection have been established, opening a new door for studying HBV infection. The fact that induced pluripotent stem cells that differentiate into hepatocyte-like cells support HBV infection provides a novel idea for the establishment of an HBV cell culture system. CONCLUSION: Because of the host and tissue specificity of HBV, a suitable in vitro HBV infection system is critical for the study of HBV pathogenesis. Nevertheless, recent advances regarding HBV infection in vitro offer hope for better studying the biological characteristics of HBV, the pathogenesis of hepatitis B, the screening of anti-HBV drugs and the mechanism of carcinogenesis.

Analysis of dynamic disturbance in blood coagulation function of patients with Coronavirus Disease 2019: A retrospective observational study.

Coronavirus Disease 2019 (COVID-19) has became a major problem affecting global health security.To assess the differences and dynamic changes of blood coagulation function in COVID-19 patients with different severity.A total of 261 COVID-19 patients from January 24 to March 25, 2020 in Huangshi, Hubei Province were enrolled.We designed a retrospective observational study. Clinical information, including age, blood routine and blood coagulation function, were collected. According to the Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China, patients were divided into 3 subgroups: 186 ordinary, 45 severe and 30 critical ones. We compared the differences in blood coagulation factors among groups.Average age in critical group (71.47 ±â€Š11.48 years) was the oldest of 3 subgroups. At admission, statistically differences could be observed among ordinary, severe and critical patients in D-dimer (0.18 ±â€Š0.33, 0.63 ±â€Š1.13 and 1.16 ±â€Š1.58 mg/L), fibrinogen/fibrin degradation products (FDP) (3.11 ±â€Š5.30, 9.82 ±â€Š23.91 and 21.94 ±â€Š40.98 µg/ml), platelet [(169 ±â€Š62.85), (188 ±â€Š71.56) and (117 ±â€Š38.31) × 10/L)] and lymphocyte count [(1.18 ±â€Š0.46), (0.82 ±â€Š0.35) and (0.75 ±â€Š0.39) × 10/L)], respectively (P < .05). During hospitalization, the peak values of coagulation and valley values of blood routine were monitored. There were significant differences among ordinary, severe and critical patients in D-dimer (0.26 ±â€Š0.46, 1.39 ±â€Š1.51 and 2.89 ±â€Š1.68 mg/L), FDP (3.29 ±â€Š5.52, 23.68 ±â€Š39.07 and 56.11 ±â€Š49.94 µg/ml), platelet [(164 ±â€Š55.53), (171 ±â€Š69.96) and (84 ±â€Š57.80) × 10/L)] and lymphocyte count [(1.10 ±â€Š0.46), (0.65 ±â€Š0.35) and (0.55 ±â€Š0.31) × 10/L)], respectively (P < .001). D-dimer and FDP in the course of disease in severe/critical groups showed a first upward and then downward trend.We concluded that coagulation function indexes such as D-dimer and FDP could be served as markers to estimate COVID-19 patients condition. Close monitoring of coagulation function may be helpful for early diagnosis of severe patients and guidance of treatments.

Comparison of Liver Biomarkers in 288 COVID-19 Patients: A Mono-Centric Study in the Early Phase of Pandemic.

Background and Aims: Recent reports have indicated that hepatic dysfunction occurred in a proportion of patients with coronavirus disease 2019 (COVID-19). We aimed to compare and describe the liver biomarkers in different subtypes of COVID-19 patients. Methods: This study enrolled 288 COVID-19 patients in Huangshi Hospital of Traditional Chinese Medicine. All patients were divided into ordinary, severe, and critical groups according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Demographic, clinical characteristics and liver biomarkers were compared among the three groups. Results: During hospitalization, AST, TBiL, and ALP levels in ordinary and severe patients fluctuated within the normal range with a rising trend in critical patients except AST. ALT and GGT levels fluctuated within the normal range showing an upward trend, while LDH levels in the critical group exceeded the normal range. Prealbumin showed an upward trend, especially in the severe group. At discharge, AST and LDH levels in ordinary and severe groups were lower than their baselines but increased in the critical group. In contrast to albumin, TBiL levels were increased in ordinary and critical groups while decreased in the severe group. The stratified analysis revealed factors affecting liver function in critical cases included highest temperature ≥38.0°C, age ≥60 and symptom of hypoxemia. Conclusions: COVID-19 can cause severe hepatic dysfunction in critical patients, requiring early monitoring and intervention. LDH, ALP, GGT, TBiL, prealbumin, and albumin may be helpful for evaluating and predicting disease prognosis due to their correlation with disease severity in COVID-19.