Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.

We report compound heterozygous variants in TOE1 in siblings of Chinese origin who presented with dyskinesia and intellectual disabilities. Our report provides further information regarding the etiology and pathogenesis of pontocerebellar hypoplasia type 7 syndrome (PCH7). Clinical manifestations were obtained, and genomic DNA was collected from family members. Whole-exome and Sanger sequencing were performed to identify associated genetic variants. Bioinformatics analysis was conducted to identify and characterize the pathogenicity of the heterozygous variants. Following long-term rehabilitation, both siblings showed minimal improvement, and their condition tended to progress. Whole-exome sequencing revealed two unreported heterozygous variants, NM_025077: c.C553T (p.R185W) and NM_025077: c.G562T (p.V188L), in the TOE1 gene mapped to 1p34.1. Sanger sequencing confirmed that the two variants in the proband and her brother were inherited from their parents. The NM_025077: c.C553T (p.R185W) variant was inherited from the father, and the NM_025077: c.G562T (p.V188L) variant was inherited from the mother. Although the two variants in the TOE1 gene have not been reported previously, they were associated with PCH7 based on integrated analysis. Thus, our report contributes to our knowledge regarding the etiology and phenotype of PCH 7.

Novel Acute Retinal Artery Ischemia and Reperfusion Model in Nonhuman Primates.

BACKGROUND AND PURPOSE: The retina, as an externally located neural tissue, offers unique advantages in investigating the effect of therapeutic intervention on the brain. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates. METHODS: Acute retinal artery ischemia and reperfusion was induced by injecting an autologous clot into the ophthalmic artery of adult rhesus monkeys, and recanalization was achieved by focal thrombolysis with tPA (tissue-type plasminogen activator). Digital subtraction angiography and fluorescein angiography were used to evaluate blood flow in the retina and the choroid. Electroretinogram, optical coherence tomography, and hematoxylin and eosin staining were used to evaluate the structure and function of the retina after ischemia. RESULTS: Digital subtraction angiography and fluorescein angiography images confirmed occlusion of the ophthalmic and central retinal arteries, as well as recanalization after tPA thrombolysis. Electroretinogram indicated retinal functional damage following ischemia, and thrombolysis partially rescued its impairment. Optical coherence tomography and hematoxylin and eosin staining revealed ischemia-induced changes in the retina, and tPA partially mitigated these damages. CONCLUSIONS: This novel acute retinal artery ischemia and reperfusion model in rhesus monkeys may closely simulate retinal ischemia/reperfusion in clinical practice and provide an optimal platform for screening neuroprotective strategies.

Transport of active particles induced by wedge-shaped barriers in straight channels with hard and soft walls.

The transport of active particles in straight channels is numerically investigated. The periodic wedge-shaped barriers can produce the asymmetry of the system and induce the directed transport of the active particles. The direction of the transport is determined by the apex angle of the wedge-shaped barriers. By confining the particles in channels with hard and soft walls, the transport exhibits similar behaviors. The average velocity is a peaked function of the translational diffusion, while it decreases monotonously with the increase of the rotational diffusion. Moreover, the simulation results show that the transport is sensitive to the parameters of the confined structures, such as the pore width, the intensity of potential, and the channel period.

Predicting neurodevelopmental outcomes for at-risk infants: reliability and predictive validity using a Chinese version of the INFANIB at 3, 7 and 10 months.

BACKGROUND: Chinese primary care settings have a heavy patient load, shortage of physicians, limited medical resources and low medical literacy, making it difficult to screen for developmental disorders in infants. The Infant Neurological International Battery (INFANIB) for the assessment of neuromotor developmental disorders in infants aged 0 ~ 18 months is widely applied in community health service centers because of its simplicity, time-saving advantages and short learning curve. We aimed to develop and assess a Chinese version of the INFANIB. METHODS: A Chinese version of the INFANIB was developed. Fifty-five preterm and 49 full-term infants with high risk of neurodevelopmental delays were assessed using the Chinese version of the INFANIB at 3, 7 and 10 months after birth. The Peabody Developmental Motor Scale (PDMS) was simultaneously used to assess the children with abnormalities and diagnose cerebral palsy. The sensitivity, specificity, positive predictive value and negative predictive value of the scale were calculated. RESULTS: At birth, a higher proportion of full-term infants had asphyxia (p < 0.001), brain damage ( p = 0.003) and hyperbilirubinemia ( p = 0.022). The interclass correlation coefficient and intraclass correlation coefficient values for the INFANIB at 3, 7 and 10 months were >0.8, indicating excellent reliability with regard to inter- and intraobserver differences. The specificity, sensitivity, positive predictive value and negative predictive value were high for both high-risk premature infants and full-term infants at the age of 10 months. For premature infants at the age of 7 months or below, INFANIB had low validity for detecting abnormalities. CONCLUSIONS: The Chinese version of the INFANIB can be useful for screening infants with high-risk for neuromotor abnormality in Chinese primary care settings.

A comparative study between traditional head measurement and structured light three-dimensional scanning when measuring infant head shape.

BACKGROUND: This study aimed to evaluate the correlation and consistency between traditional head measurement and structured light three-dimensional (3D) scanning parameters when measuring infant skull shape. METHODS: A total of 76 infants aged 3 months to 2.5 years old were included in the study. Head circumference (HC) was measured with a tape measure. The transverse, anteroposterior, and oblique diameters were measured using a spreading caliper, and the cranial vault asymmetry index (CVAI) and a cranial index (CI) of symmetry were calculated; 76 cases were measured successfully. The above indexes were measured using a structured light 3D scanning system (71 cases were measured with success). Thus, in the end, the valid data of 71 cases were analyzed, and the measurements of the two approaches were compared. RESULTS: The 95% confidence interval of traditional head measurement and structured light 3D scanning was between 0.633 and 0.988. Pearson's correlation coefficient indicated a high correlation between the two methods (r=0.793-0.980). The correlation coefficients of the transverse diameter, anteroposterior diameter, and HC, and the CI of symmetry were higher than 0.9. The lowest correlation coefficient for the CVAI was 0.793. The P values of the above measurement data were all <0.001, which indicated that they were closely related. A Bland-Altman plot indicated reasonable consistency between the two methods. CONCLUSIONS: Both traditional head measurement and structured light 3D scanning are suitable for the measurement of infant head shape. However, while traditional head measurement using a spreading caliper is economical and simple, making it suitable for general screening at a basic level, structured light 3D scanning can deliver additional parameters, which is useful for infants with an abnormal head shape. The latter is also convenient for designing a customized helmet for skull correction when needed.

Long non-coding RNA LINC00460 predicts poor survival and promotes cell viability in pancreatic cancer.

Emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) possess great potential as vital biomarkers and powerful therapeutic targets in various diseases. In the present study, differentially expressed transcripts in pancreatic cancer (PC) were identified, and a competing endogenous RNA (ceRNA) network was constructed using The Cancer Genome Atlas database. An independent cohort consisting of 59 patients with PC was used to validate the clinical value of the identified lncRNA. Cell viability and colony formation assays were used to evaluate the biological functions of the lncRNA in PC cells. The present bioinformatic analysis revealed that LINC00460 was upregulated in PC samples with a prognostic significance. In the ceRNA network, it potentially targeted the microRNA-503/cyclin D1 axis. The results of real-time quantitative PCR confirmed that LINC00460 was significantly upregulated in cancer tissues and was associated with poor survival of patients with PC. The expression levels of LINC00460 were significantly associated with tumor size, but not with age, sex, differentiation, lymph node metastasis, vascular invasion and tumor stage. Through univariate and multivariate analysis, LINC00460 was characterized as an independent prognostic biomarker for PC. Further in vitro experiments demonstrated that suppressing LINC00460 using small interfering RNA inhibited viability and colony formation of PC cells. In summary, LINC00460 may be an independent prognostic biomarker for PC and may serve as an oncogenic lncRNA that promotes PC cell growth. Further in-depth exploration is required to reveal the specific biological mechanism of LINC00460 in PC cells.

Identification of key candidate genes for pancreatic cancer by bioinformatics analysis.

Although pancreatic cancer has the highest mortality rate among all neoplasms worldwide, its exact mechanism remains poorly understood. In the present study, three Gene Expression Omnibus (GEO) datasets were integrated to elucidate the potential genes and pathways that contribute to the development of pancreatic cancer. Initially, a total of 226 differentially expressed genes (DEGs) were identified in the three GEO datasets, containing 179 upregulated and 47 downregulated DEGs. Furthermore, function and pathway enrichment analyses were performed to explore the function and pathway of these genes, and the results indicated that the DEGs participated in extracellular matrix (ECM) processes. In addition, a protein-protein interaction network was constructed and 163 genes of the 229 DEGs were filtered into the network, resulting in a network complex of 163 nodes and 438 edges. Finally, 24 hub genes were identified in the network, and the top 2 most significant modules were selected for function and pathway analysis. The hub genes were involved in several processes, including activation of matrix, degradation of ECM and ECM organization. Taken collectively, the data demonstrated potential key genes and pathways in pancreatic cancer, which may provide novel insights to the mechanism of pancreatic cancer. In addition, these hub genes and pathways may be considered as targets for the treatment of pancreatic cancer.

Anti-tumor effects of engineered mesenchymal stem cells in colon cancer model.

BACKGROUND: Cell-based gene therapy is considered as a promising strategy for the treatment of human malignancy. In many different types of cancer, mesenchymal stem cells (MSCs) are observed as valuable and potential anti-cancer agents. However, the exact mechanisms of MSCs involved in tumor microenvironment are not well understood. AIM: Our aims are to elucidate the MSCs-mediated tumor microenvironment. MATERIALS AND METHODS: In this study, colon cancer model was established by injecting the HT29 cells into the subcutaneous of right axilla of nude mice. We applied the human placenta-derived MSCs (hP-MSCs) armed with a double fusion gene containing the herpes simplex virus truncated thymidine kinase and firefly luciferase for treatment of colon cancer on days 10, 15, and 20 after HT29 cells injection. Molecular imaging methods were used for real-time imaging tumor progression and tracking transplanted hP-MSCs by bioluminescence imaging. Furthermore, proliferation and apoptosis-related proteins levels in colon cancer tissues were examined by immunofluorescence and Western blotting. RESULTS: Our results demonstrated that the administration of engineered hP-MSCs significantly inhibited the tumors and this effect was enhanced by ganciclovir application. Further analysis demonstrated the anti-tumor effect of engineered hP-MSCs in vivo depended on inhibiting tumor proliferation and inducing tumor apoptosis. CONCLUSION: Collectively, this work showed that engineered hP-MSCs could inhibit colon cancer progression and metastasis by inducing tumor cell death and suppressing proliferation.

Low-frequency stimulation of bilateral anterior nucleus of thalamus inhibits amygdale-kindled seizures in rats.

Brain stimulation with low-frequency is emerging as an alternative treatment for refractory epilepsy. The anterior nucleus thalamus (ANT) is thought to be a key structure in the circuits of seizure generation and propagation. The present study aimed to investigate the effects of low frequency stimulation (LFS) targeting ANT on amygdala-kindled seizures in Sprague-Dawley rats. Electrodes were implanted into the right basolateral amygdala and the right or bilateral ANT of Sprague-Dawley rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, LFS (15 min train of 0.1 ms pulses at 1 Hz and 200-500 µA) was applied to the unilateral or bilateral ANT immediately before the kindling stimulation (pre-treatment). Our study showed that LFS of the bilateral ANT significantly decreased the incidence of generalized seizures (GS) and seizure stage, as well as shortened duration of afterdischarge and GS demonstrating an inhibition of the severity of seizures. Moreover, LFS elevated the afterdischarge threshold (ADT) and GS threshold indicating an inhibition of susceptibility to seizures. On the other hand, LFS of the unilateral ANT failed to show any significance in inhibiting seizures. Our study demonstrated that bilateral LFS in ANT could significantly inhibit amygdala-kindled seizures by preventing both afterdischarge generation and propagation. It provided further evidence for clinical use of LFS in ANT.

Isoprene polymerization with aminopyridinato ligand supported rare-earth metal complexes. Switching of the regio- and stereoselectivity.

The highly cis-1,4, trans-1,4 and 3,4-selective polymerizations of isoprene were successfully regulated by simply modifying the auxiliary ligands, metal centres and initiation groups of rare-earth metal complexes and cocatalysts.