OBJECTIVE: To explore the clinical phenotype and genetic characteristics in two children with Knobloch syndrome (KNO) due to variants of COL18A1 gene. METHODS: Two children presented at the Genetic Eye Disease Clinic of the Eye Hospital of Wenzhou Medical University in October 2023 for ocular lesions were selected as the study subjects. Relevant clinical data and peripheral venous blood samples were collected from the children and their parents. Following genomic DNA extraction, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of the family members. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-212-K-185). RESULTS: Both children exhibited characteristic ocular features of KNO including nystagmus, high myopia, and leopard spot fundus. Additionally, child 1 also presented with congenital occipital bone dysplasia and occipital encephalocele, while child 2 was diagnosed with vitreoretinochoroidopathy and bilateral high myopia. WES has identified compound heterozygous variants of the COL18A1 gene in both children, including a c.3013+3A>C splice-site variant and a c.2743C>T (p.Arg915Ter) nonsense variant in child 1, and a novel c.1702-1G>A splice-site variant and a c.3836C>T (p.Ser1279Leu) missense variant in child 2. A comprehensive literature review has identified 63 domestic and international articles involving 167 patients with KNO whom can be classified into three subtypes, with KNO type I being the most common and caused by pathogenic variants in the COL18A1 gene. Both probands in this study were children with KNO type I. Analysis of the genotype-phenotype correlations and population distribution characteristics revealed that the KNO patients exhibited significant clinical and genetic heterogeneity, along with a broad geographic distribution, with a relatively greater number of cases reported in Brazil and China. and a broad geographic distribution, with the highest numbers reported in Brazil and China. While no significant difference in genotype distribution was observed between Chinese and non-Chinese patients, phenotypic disparities were noted, with the non-Chinese cohort showing significantly higher rates of retinal detachment and developmental delay (P < 0.05), whereas Chinese patients exhibited a greater proportion of macular hypoplasia (P < 0.05). CONCLUSION The main clinical manifestations of KNO include high myopia, vitreoretinal dystrophy, and occipital encephalocele. The novel c.1702-1G>A splice-site variant identified in the COL18A1 gene has expanded the mutational spectrum of KNO type I and provided valuable insights for genetic diagnosis, counseling, and clinical management of the disease.
Humans ; Retinal Detachment/congenital* ; Male ; Female ; Child ; Encephalocele/genetics* ; Exome Sequencing ; Collagen Type XVIII/genetics* ; Phenotype ; Retinal Degeneration/genetics* ; Mutation ; Child, Preschool

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.

Objective:To overcome the disadvantages of bismuth removal by bismuth sulfide precipitation method recommended by existing analytical standards and improve the quality of analytical result.Methods:Based on 201×7 anion exchange resin, the experimental process of bismuth removal was designed, and verified by using spiked samples and IAEA test samples.Results:Bismuth was removed by anion exchange resin. In the removal experiments of strontium, yttrium and bismuth, the chemical recovery rate of strontium and yttrium could reach (98.6 ± 0.8)% and (98.5 ± 0.7)%, respectively, with no Bi 2S 3 precipitation found. The relative standard deviation between analytical result and theoretical values was -2.97% to 5.94%, better than 3.96%-17.8% by the standard bismuth removal method. Through validation using IAEA test samples, the relative standard deviation between the reported value and the target value for 90Sr was between 3.40%-7.09%, and all the results were acceptable. Conclusions:Bismuth could be quantitatively removed using anion exchange resin without adsorption of strontium and yttrium. In addition, the bismuth removal solution system of anion exchange resin was the same as the elution system in 90Sr analysis, and the purpose of rapid bismuth removal could be achieved without conversion system. Compared with the current standard analytical method, it was feasible and better to quantitatively remove bismuth based on anion exchange resin, which could meet the needs of routine analysis of 90Sr.

Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-β promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-β activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-β signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.
Cells, Cultured ; Gene Library ; Humans ; Interferon Type I ; metabolism ; Interferon-beta ; genetics ; metabolism ; Proto-Oncogene Proteins c-pim-1 ; genetics ; Up-Regulation

Objective To investigate the protective function of edaravone in the compressed spinal cord.Methods There were 150 rabbits enrolled in each group in the experiment.Rabbits in both operation group and edaravone (EDA) treating group received mild spinal cord compressionby setting a flap head screw between C6 C7 after the neck.The spinal cord decompression was conducted seven days later.After 6 hours,rabbits in the EDA treating group were injected with a large amount of EDA through ear border veins,while the rabbits in the operation group only received 0.9％ sodium chloride injection.The transmission electron microscope was used to observe the apoptotic bodies at 1 day,3 days and 7 days after compression,and 1 day,3 days,7 days,and 14 days after decompression.Flow cytometry was used to test the rate of apoptosis of spinal cord cells.Immunohistochemistry was used to test the expression of Bax protein that is related to apoptosis.Results The neuronal apoptosis appeared after compression in both operation group and EDA-treating group.The Basso Beattie Bresnahan (BBB) score,neuronal apoptosis rates,and Bax protein expressions in both groups were statistically different (P ＜ 0.05) when the spinal cord was compressed in the first day and the third day,while there was no statistically different when spinal cord compressed at the seventh day (P ＞ 0.05).After decompression of the spinal cord,the BBB score,neuronal apoptosis rates,and Bax protein expressions in both groups were becoming lower at the seventh day (P ＜0.05).Conclusions EDA has protective function for compressed spinal cord.However,only the compression of spinal cord compression period of sufficient decompression can fundamentally protect the spinal cord.

Objective To compare different incidence between lateral position and horizontal position in the Burr holes irrigation drainage(BHID).The BHID is wildly known as the most frequently used neurosurgical treatment of chronic subdural hematoma(CSDH).Methods A total of 80 cases were selected which were undergone BHID during January 2010 and December 2015,and the incidence of intracranial pneumatocele was compared after operation.All of cases came from the Second People′s Hospital of Tai Zhou City.Results There were 5 cases(out of 50,10%)having moderate intracranial pneumocephalus but no numerous intracranial pneumocephalus in lateral position,while 26 cases(out of 30 cases,87%)in horizontal position emerging moderate amount or more intracranial pneumatocele.And there were 8 cases'numerous pneumatocele in the horizontal postion group.There was no tension pneumothorax emerging in both groups.Both groups had statistical difference (χ2 =46.43,P <0.01.Conclusion BHID in lateral postion is a simple and effective method for CSDH,and it is conducive to reduce postoperative intracranial pneumatosis.That is worthy of application and promotion.

Objective To evaluate the correlation between diffusion tensor imaging(DTI)measurements,fiber tracking(FT)and the clinical symptoms in patients with cervical spondylotic myelopathy.Methods According to the Japanese orthopaedics association score(JOA),104 patients with cervical spondylopathy were divided into 4 groups:mild in 31 patients with 13-16 scores,moderate in 27 with 9-12 scores,severe in 25 with 5-8 scores,and serious in 21 with 0-4 scores.According to the lesion signal characters,all patients were divided into 3 groups:Group A with normal signal in both T1 WI and T2WI in 33 patients,Group B with normal signal in T1WI but high signal in T2WI in 30 patients,and Group C with low signal in T1 WI and high signal in T2WI in 41 patients.Apparent diffusion coefficient (ADC),fractional anisotropy(FA),λ1,λ2,λ3 were measured in the spinal cord at the serious pressed section,and fiber tractography was performed.The Spearman correlation analyses was used to correlate each of the DTI measurement with JOA score.Group difference was tested with one-way ANOVA method.Results High quality of DTI was acquired in all patients.The FA values in the mild,moderate,severe,and serious groups were respectively 0.69 ±0.13,0.58 ±0.03,0.46 ±0.08,and 0.37 ±0.11 and significant difference was found in different groups(F =100.59,P ＜ 0.05)and positively correlated with JOA scores (r =0.883,P ＜ 0.05).There was no statistical significance between JOA scores and ADC,λ1,λ2,λ3(r=0.232,0.217,0.113,0.127,P ＞0.05).The FA values in group A,B,and C were respectively 0.67 ±0.33,0.51 ±0.21,0.38 ±0.03,and significant difference was found among different groups(F =50.05,P ＜ 0.05).Decrease of JOA score and high signal in T2 companied with decrease of FA value.Decrease of FA values was found associated with increase of fiber bundle damage.The ADC,λ2,λ3 but not λ1 were significantly different among the JOA groups and the group A,B,and C.Conclusions The FA values are positively correlated with clinical symptoms.Decrease of FA values is found associated with increase of fiber bundle damage.DTI can show the severity and extent of damage of spinal cord in patients with cervical spondylotic myelopathy.

Objective To explore the value of CT spinal angiography with 256 MSCT and fast dynamic contrast-enhanced 3D MR angiography (CE-MRA) at 3.0 T in the diagnosis of spinal vascular malformations by comparing with results of DSA and operation.MethodsSeventeen patients suspected of spinal vascular diseases by initial MR and clinical manifestations all underwent CT spinal angiography.Of them,10 patients underwent MRA,15 patients underwent DSA within 3-5 days,and 8 patients finally underwent surgical treatment.ResultsCTA examination clearly showed the abnormal vascular lesions in 16 of 17 cases,including 7 cases with the diagnosis of spinal dural arteriovenous fistula,7 cases of perimedullary arteriovenous fistula,and 2 cases of spinal arteriovenous malformations. The results were consistent with the diagnosis of DSA or surgery.One case was poorly diagnosed.The feeding vessels were correctly determined in 12 cases,and the level of fistulas were correctly displayed in 12 cases.The level of fistulas and feeding vessels were accurately showed in 7 of 10 cases with MRA,while the other 3 cases exhibited normal with DSA.ConclusionsSpinal angiography with 256 MSCT and CE-MRA at 3.0 T can clearly show the extent of spinal vascular malformations,feeding arteries and fistula location.They are safe,noninvasive,convinient and can shorten the time of DSA diagnosis and treatment.They play an important role in diagnosis and treatment of spinal vascular malformations and postoperative follow-up.