Novel TP53RK variants cause varied clinical features of Galloway-Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients.

Objectives: Galloway-Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by TP53RK gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterious variants in TP53RK) have been reported. This study aimed to examine the clinical and genetic characteristics of three unrelated GAMOS4 patients with TP53RK gene compound heterozygous mutations. Methods: Whole-exome sequencing (WES) was used to identify four novel TP53RK variants in three unrelated Chinese children. Clinical characteristics such as biochemical parameters and image findings of patients were also evaluated. Furthermore, four studies of GAMOS4 patients with TP53RK variants were reviewed. In addition, clinical and genetic features were described after a retrospective analysis of clinical symptoms, laboratory data, and genetic test results. Results: The three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. Furthermore, patient 1 had slight proteinuria, while patient 2 had epilepsy. However, none of the individuals had nephrotic syndrome, and all were alive for more than 3 years of age. This is the first study to assess four variants in the TP53RK gene (NM_033550.4: c.15_16dup/p.A6Efs*29, c.745A > G/p.R249G, c.185G > A/p.R62H, and c.335A > G/p.Y112C). Conclusion: The clinical characteristics of the three children with TP53RK mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. This study provides insights into the pathogenic TP53RK gene mutation spectrum and clinical phenotypes of GAMOS4.

Bioaugmentation combined with biochar to enhance thermophilic hydrogen production from sugarcane bagasse.

In this study, Thermoanaerobacterium thermosaccharolyticum MJ2 and biochar were used to enhance thermophilic hydrogen production from sugarcane bagasse. MJ2 bioaugmentation notably increased the hydrogen production by 95.31%, which was further significantly improved by 158.10% by adding biochar. The addition of biochar promoted the degradation of substrate, improved the activities of hydrogenase and electron transfer system, and stimulated microbial growth and metabolism. Microbial community analysis showed that the relative abundance of Thermoanaerobacterium was significantly increased by bioaugmentation and further enriched by biochar. PICRUSt analysis showed that MJ2 combined with biochar promoted metabolic pathways related to substrate degradation and microbial metabolism. This study provides a novel enhancement method for hydrogen production of the cellulolytic microbial consortium by exogenous hydrogen-producing microorganism combined with biochar and deepens the understanding of its functional mechanism.

Three-year clinical observation of the outcomes of transepithelial and epithelial-off accelerated corneal collagen crosslinking treatment for different types of progressive keratoconus.

In the present study, the clinical and long-term effects of accelerated transepithelial corneal collagen crosslinking (ATE-CXL) and accelerated epithelial-off corneal collagen crosslinking (A-CXL) for the treatment of different types of progressive keratoconus were compared. A total of 70 patients, including 96 eyes with advanced keratoconus, were enrolled in the study. ATE-CXL or A-CXL was performed on one or two eyes of each subject according to corneal thickness, keratoconus type and surgical approach. Patients were divided into the following four groups: Group A, ATE-CXL for central keratoconus; group B, A-CXL for central keratoconus; group C, ATE-CXL for peripheral keratoconus; and group D, A-CXL for peripheral keratoconus. Uncorrected distant visual acuity (UDVA), best-corrected distant (BD)VA and corneal astigmatism (CA) were evaluated in all patients by routine ophthalmology pre-operatively and 3 years post-operatively. Topographical features, including maximum corneal curvature (Kmax), thinnest corneal thickness (TCT), anterior corneal elevation (ACE) and corneal endothelial cell density (ECD) were also compared across groups. The results suggested that pre- and post-operative UDVA, BDVA, Kmax, CA and ACE values differed in all four groups (P<0.05), whereas no differences were observed between pre- and post-operative TCT and ECD (P>0.05). Concordant results were obtained between groups A and C and groups B and D. ATE-CXL achieved better control of central keratoconus UDVA, Kmax and CA as compared with A-CXL. The difference between pre- and post-operative UDVA, Kmax and CA as compared with A-CXL was highly correlated with the change in intraocular pressure and treatment effectiveness. There was a statistically significant improvement in BDVA with ATE-CXL for treatment of central keratoconus compared with that after A-CXL treatment (P=0.032). There were statistically significant improvements in BDVA (P=0.047), CA (P=0.045) and ACE (P=0.012) with A-CXL treatment of peripheral keratoconus when compared with ATE-CXL treatment. Central, and to a lesser extent, peripheral, keratoconus may be effectively controlled by either approach, with disease stabilization 3 years later. ATE-CXL is suggested to be the most suitable treatment for keratoconus of <400 µm with a corneal thickness of >400 µm; however, A-CXL yields superior long-term outcomes.

[Effect of Biofeedback Combined with Task-oriented Training on Hand Function, Gesell Scale Score and Balance Ability in Children with Spastic Cerebral Palsy].

OBJECTIVE: To analyze the effects of biofeedback combined with task-oriented training on hand function, Gesell's infant development scale score (Gesell) and balance ability in children with spastic cerebral palsy (SCP). METHODS: 66 children with SCP admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group. The control group ( n=33) received conventional rehabilitation treatment, and the observation group ( n=33) received biofeedback combined with task-oriented training based on the treatment of control group. After 6-month treatment, Modified Ashworth scale (MAS) score, Berg balance scale (BBS) score, standing and walking function score in gross motor function scale (GMFM), assisting hand assessment scales (AHA) score, Gesell scale score and satisfaction of the children's parents were compared between the two groups. RESULTS: The MAS score after treatment was lower than that before treatment in both two groups ( P<0.05), and the BBS score after treatment was higher than that before treatment in both two groups ( P<0.05). After treatment, the MAS score in the observation group was lower than the control group, and the BBS score in the observation group was higher than the control group ( P<0.05). The scores of standing and walking function after treatment were higher than that before treatment in both two groups ( P<0.05). After treatment, the scores of standing and walking function in the observation group were higher than the control group ( P<0.05). The AHA score and Gesell developmental quotient (DQ) score after treatment were higher than that before treatment in both two groups ( P<0.05). After the treatment, the AHA score and Gesell DQ score in the observation group were higher than the control group ( P<0.05). The satisfaction rate of rehabilitation treatment in the observation group was higher than the control group (90.91% vs. 60.61%, P<0.05). CONCLUSION: Biofeedback combined with task-oriented training can improve balance ability, spasm relieve, hand function, development level, standing and walking function in the children with spastic cerebral palsy and increase the treatment satisfaction degree of children's guardians.