Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis.

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism.

Simulated spaceflight-induced cardiac remodeling is modulated by gut microbial-derived trimethylamine N-oxide.

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.

Yersinia pestis and Plague: some knowns and unknowns.

Since its first identification in 1894 during the third pandemic in Hong Kong, there has been significant progress of understanding the lifestyle of Yersinia pestis, the pathogen that is responsible for plague. Although we now have some understanding of the pathogen's physiology, genetics, genomics, evolution, gene regulation, pathogenesis and immunity, there are many unknown aspects of the pathogen and its disease development. Here, we focus on some of the knowns and unknowns relating to Y. pestis and plague. We notably focus on some key Y. pestis physiological and virulence traits that are important for its mammal-flea-mammal life cycle but also its emergence from the enteropathogen Yersinia pseudotuberculosis. Some aspects of the genetic diversity of Y. pestis, the distribution and ecology of plague as well as the medical countermeasures to protect our population are also provided. Lastly, we present some biosafety and biosecurity information related to Y. pestis and plague.

Body weight, weight change and the risk of cardiovascular disease in patients with hypertension: a primary-care cohort study.

BACKGROUND/OBJECTIVES: Obesity and cardiovascular disease (CVD) often co-occur. However, the effects of excessive body weight and weight change on CVD in patients with hypertension are not clearly established. We examined the associations of BMI, weight change and the risk of CVD in patients with hypertension. SUBJECTS/METHODS: Our Data were drawn from the medical records of primary-care institutions in China. A total of 24,750 patients with valid weight measurements attending primary healthcare centers were included. Body weight were grouped in BMI categories of underweight ( < 18.5 kg/m2), healthy weight (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2) and obesity ( ≥ 25.0 kg/m2). Weight change over 12 months was divided into: gain >4%, gain 1-4%, stable (-1 to 1%), loss 1-4%, and loss ≥4%. Cox regression analyses were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI) between BMI, weight change and the risk of CVD. RESULTS: After multivariable adjustment, patients with obesity were related to higher risks of CVD (HR = 1.48, 95% CI: 1.19-1.85). Higher risks were seen in participants with loss ≥4% and gain >4% of body weight compared to stable weight (loss ≥4%: HR = 1.33, 95% CI: 1.04-1.70; gain >4%: HR = 1.36, 95% CI: 1.04-1.77). CONCLUSION: Obesity and weight change of loss ≥4% and gain >4% were related to higher risks of CVD. Close monitoring and appropriate interventions aimed at achieving an optimal weight are needed to prevent adverse cardiovascular outcomes for patients with hypertension.

[Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene].

OBJECTIVE: To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene. METHODS: A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4). CONCLUSION: The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

Preparation of polyclonal antibody against a universal bacterial antigen OmpA deduced by bioinformatic analysis and preliminary evaluation of concentration effects on foodborne pathogens.

Rapid and ultrasensitive microbial detection in actual samples have challenges because of target pathogen diversity and low abundance. In this study, we attempted to capture and concentrate multiple pathogens by combining magnetic beads with polyclonal antibodies against a universal antigen of ompA, LAMOA-1, before further detection. A protein sequence consisting of 241 amino acids with spatial conformation similar to E. coli ompA was identified and expressed as a recombinant protein in prokaryotes according to the results of sequence alignment among 432 sequences of ompA belonging to intestinal bacteria from gram-negative bacteria. Purified from immunized rabbits, the anti-LAMOA-1 antibody was shown to effectively recognize 12 foodborne bacterial species. Antibody-conjugated beads were used to concentrate the bacteria when the bacterial concentration in artificially contaminated samples is between 10 and 100 CFU/mL, which shortens detection duration by 8-24 h. The enrichment strategy is potentially beneficial for detection of foodborne pathogens.

Effects of 60 days of 6° head-down bed rest on the composition and function of the human gut microbiota.

Spaceflight is rigorous and dangerous environment which can negatively affect astronauts' health and the entire mission. The 60 days of 6° head-down bed rest (HDBR) experiment provided us with an opportunity to trace the change of gut microbiota under simulated microgravity. The gut microbiota of volunteers was analyzed and characterized by 16S rRNA gene sequencing and metagenomic sequencing. Our results showed that the composition and function of the volunteers' gut microbiota were markedly was affected by 60 days of 6° HDBR. We further confirmed the species and diversity fluctuations. Resistance and virulence genes in the gut microbiota were also affected by 60 days of 6° HDBR, but the species attributions remained stable. The human gut microbiota affected by 60 days of 6° HDBR which was partially consistent with the effect of spaceflight, this implied that HDBR was a simulation of how spaceflight affects the human gut microbiota.

Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age.

Brain aging may accelerate after rodents reach middle age. However, the endogenous mediator that promotes this acceleration is unknown. We predict that the mediator may be expressed after an organism reaches middle age and dysregulates mitochondrial function. In the neurons of wild-type Drosophila (flies), we observed that mitochondria were fragmented in aged flies, and this fragmentation was associated with mitochondrial calcium overload. In a previous study, we found that mitochondrial fragmentation induced by calcium overload was reversed by the loss of Vimar, which forms a complex with Miro. Interestingly, Vimar expression was increased after the flies reached middle age. Overexpression of Vimar in neurons resulted in premature aging and mitochondrial calcium overload. In contrast, downregulation of Vimar in flies older than middle age promoted healthy aging. As the mouse homolog of Vimar, RAP1GDS1 expression was found to be increased after mice reached middle age; RAP1GDS1-transgenic and RAP1GDS1-knockdown mice displayed similar responses to flies with overexpressed and reduced Vimar expression, respectively. This research provides genetic evidence of a conserved endogenous mediator that promotes accelerated brain aging.

The impact of COVID lockdown on glycaemic control in paediatric patients with type 1 diabetes: A systematic review and meta-analysis of 22 observational studies.

Introduction: The COVID lockdown has posted a great challenge to paediatric patients with type 1 diabetes (T1D) and their caregivers on the disease management. This systematic review and meta-analysis sought to compare the glycaemic control among paediatric patients with T1D (aged under 18 years) pre- during, and post-lockdown period. Methods and materials: We did a systematic search of three databases (PubMed, Embase, and the WHO COVID-19 Global literature) for the literature published between 1 Jan 2019 to 10 Sep 2022. Studies meeting the following inclusion criteria were eligible for this study: (1) a COVID-19 related study; (2) inclusion of children aged 18 years old or under with established T1D; (3) comparing the outcomes of interest during or after the COVID lockdown with that before the lockdown. Study endpoints included mean difference (MD) in HbA1c, blood glucose, time in range (TIR, 70-180 mg/dl), time above range (TAR, >180mg/dl), time below range (TBR,<70mg/dl) and glucose variability (coefficient of variation [CV]) between pre-lockdown and during lockdown and/or between pre- and post-lockdown period. The MD and its corresponding 95% CI of each endpoint were pooled using random-effect model considering the potential between-study heterogeneity in COVID restrictions and T1D management. Results: Initial search identified 4488 records and 22 studies with 2106 paediatric patients with T1D were included in the final analysis. Compared with pre-lockdown period, blood glucose was significantly decreased by 0.11 mmol/L (95%CI: -0.18, -0.04) during lockdown period and by 0.42 mmol/L (95%CI: -0.73, -0.11) after lockdown. The improvement was also found for TIR, TAR, TBR, and CV during and post-lockdown (all p values<0.05) except for the post-lockdown TBR (p =0.35). No significant change in HbA1c was observed during and post- lockdown period when compared with the pre-lockdown value. There was moderate to high between-study heterogeneity for most of the analyses. Conclusion: Compared with pre-lockdown period, there was significant improvement in T1D paediatric patients' glucose metrics during and post-lockdown. The underlying reasons for this positive impact warrant further investigation to inform future paediatric diabetes management. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022359213.

Comparison of the Efficacy of Different Insulin Administration and Blood Glucose Monitoring Methods in the Treatment of Type 1 Diabetes Mellitus in Children.

Objective: To compare the clinical efficacy of different insulin administration methods and blood glucose monitoring methods in treating type 1 diabetes mellitus in children. Methods: Patients were divided into four groups: multiple daily injection (MDI) + fingertip blood glucose detection, continuous subcutaneous insulin infusion (CSII) + fingertip blood glucose detection, MDI + continuous glucose monitoring system (CGMS), and CSII + CGMS. After six months of treatment, followed by telephone and at least once a month in an outpatient clinic, insulin doses were adjusted according to the children's blood glucose levels. Blood glucose control and the daily dose of insulin were compared among the four groups after treatment, and the incidence of hypoglycemia in each group was recorded during the treatment. We also compare the incidence of the adverse event among the four groups. Results: 6 months later, the levels of HbA1c, FBG, and two h PG in each group were lower than those before treatment. There were significant differences in HbA1c, two h PG, and the daily insulin dose among the four groups. There were differences in the frequency of hypoglycemia among all the groups. The frequency of hypoglycemia in groups C and D was lower than in group A. Conclusions: CSII was better than MDI, and the blood glucose monitoring effect of CGMS was better than the fingertip blood glucose detection. The patients treated with CSII combined with CGMS had the best clinical efficacy. The patients treated with CSII combined with CGMS had the lowest adverse events incidence.

The Risks of Cardiovascular Disease Following Weight Change in Adults with Diabetes: A Cohort Study and Meta-analysis (jc.2022-01089).

CONTEXT: Weight management is recognized as critical in reducing cardio-metabolic risk factors for adults with diabetes, but the effects of weight change on cardiovascular disease in patients with diabetes are unknown. OBJECTIVE: To evaluate 18-month weight change and subsequent risk of macrovascular and microvascular complications in established individuals with type 2 diabetes. DESIGN AND SETTING: This study consisted of a cohort study and a meta-analysis. In the cohort study, weight change over 18 months was divided into: gain ≥5%, gain 1%-5%, stable (-1%-1%), loss 1%-5%, and loss ≥5%. Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We then used random-effect models to pool the results combing our study with other relevant studies. RESULTS: In the cohort study, 8920 participants with valid weight measurements were included. Compared with patients with stable weight, higher risks were seen in those with weight change for total vascular complications (gain ≥5%: HR=1.43, 95% CI: 1.10-1.85; gain 1-5%: HR=1.44, 95% CI: 1.02-2.03; loss ≥5%: HR=1.58, 95% CI: 1.20-2.08), macrovascular complications (gain ≥5%: HR=1.84, 95% CI: 1.16-2.91; loss 1-5%: HR=1.91, 95% CI: 1.06-3.43; loss ≥5%: HR=2.18, 95% CI: 1.36-3.49) and microvascular complications (loss ≥5%: HR=1.48, 95% CI: 1.06-2.06). Meta-analysis also showed similar results. CONCLUSIONS: Weight gain and loss over 18 months among patients with type 2 diabetes, especially weight change ≥5%, may be a warning sign of adverse cardiovascular outcomes.

The Risks of Cardiovascular Disease Following Weight Change in Adults with Diabetes: A Cohort Study and Meta-analysis.

CONTEXT: Weight management is recognized as critical in reducing cardio-metabolic risk factors for adults with diabetes, but the effects of weight change on cardiovascular disease in patients with diabetes are unknown. OBJECTIVE: To evaluate 18-month weight change and subsequent risk of macrovascular and microvascular complications in established individuals with type 2 diabetes. DESIGN AND SETTING: This study consisted of a cohort study and a meta-analysis. In the cohort study, weight change over 18 months was divided into: gain ≥5%, gain 1%-5%, stable (-1%-1%), loss 1%-5%, and loss ≥5%. Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). We then used random-effect models to pool the results combing our study with other relevant studies. RESULTS: In the cohort study, 8920 participants with valid weight measurements were included. Compared with patients with stable weight, higher risks were seen in those with weight change for total vascular complications (gain ≥5%: HR=1.43, 95% CI: 1.10-1.85; gain 1-5%: HR=1.44, 95% CI: 1.02-2.03; loss ≥5%: HR=1.58, 95% CI: 1.20-2.08), macrovascular complications (gain ≥5%: HR=1.84, 95% CI: 1.16-2.91; loss 1-5%: HR=1.91, 95% CI: 1.06-3.43; loss ≥5%: HR=2.18, 95% CI: 1.36-3.49) and microvascular complications (loss ≥5%: HR=1.48, 95% CI: 1.06-2.06). Meta-analysis also showed similar results. CONCLUSIONS: Weight gain and loss over 18 months among patients with type 2 diabetes, especially weight change ≥5%, may be a warning sign of adverse cardiovascular outcomes.

Changes in Higher-Order Chromosomal Structure of Klebsiella pneumoniae Under Simulated Microgravity.

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.

Attenuation of Yersinia pestis fyuA Mutants Caused by Iron Uptake Inhibition and Decreased Survivability in Macrophages.

Yersinia pestis is the etiological agent of plague, a deadly infectious disease that has caused millions of deaths throughout history. Obtaining iron from the host is very important for bacterial pathogenicity. Y. pestis possesses many iron uptake systems. Yersiniabactin (Ybt) plays a major role in iron uptake in vivo and in vitro, and in virulence toward mice as well. FyuA, a ß-barrel TonB-dependent outer membrane protein, serves as the receptor for Ybt. In this study, we examined the role of the fyuA gene in Y. pestis virulence using different challenging ways and explored the underlying mechanisms. The BALB/c mouse infection assay showed that the virulence of the mutant strains (ΔfyuA and ΔfyuAGCAdel) was lower when compared with that of the wild-type (WT) strain 201. Furthermore, the attenuation of virulence of the mutant strains via subcutaneous and intraperitoneal challenges was far greater than that via intravenous injection. Iron supplementation restored lethality during subcutaneous challenge with the two mutants. Thus, we speculated that the attenuated virulence of the mutant strains toward the mice may be caused by dysfunctional iron uptake. Moreover, ΔfyuA and ΔfyuAGCAdel strains exhibited lower survival rates in murine RAW264.7 macrophages, which might be another reason for the attenuation. We further explored the transcriptomic differences between the WT and mutant strains at different temperatures and found that the expressions of genes related to Ybt synthesis and its regulation were significantly downregulated in the mutant strains. This finding indicates that fyuA might exert a regulatory effect on Ybt. Additionally, the expressions of the components of the type III secretion system were unexpectedly upregulated in the mutants, which is inconsistent with the conventional view that the upregulation of the virulence genes enhances the virulence of the pathogens.

PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

miR-126-5p Targets SP1 to Inhibit the Progression of Parkinson's Disease.

BACKGROUND: At present, symptomatic treatment may improve the life quality of Parkinson's disease (PD) patients to a certain extent but cannot completely cure PD. Therefore, it is urgent medical problem to be solved for improving the efficacy and safety of PD treatment. METHODS: SH-SY5Y and SK-N-SH cells were treated with 1-methyl-4-phenylpyridinium (MPP+) to establish PD model cells. miR-126-5p and specific protein-1 (SP1) expression levels were detected by quantitative Real-Time PCR (qRT-PCR). Western blot was applied to measure protein levels of SP1, Bax, and Bcl-2. The viabilities and apoptosis rates of treated cells were measured using cell counting kit-8 assay and flow cytometry analysis. Enzyme-linked immunosorbent assay was performed to measure TNF-α and IL-1ß releases. Interaction between miR-126-5p and SP1 was examined by dual-luciferase reporter assay. RESULTS: MPP+ treatment greatly downregulated miR-126-5p expression while upregulated SP1 expression in SH-SY5Y and SK-N-SH cells in a time- and does-dependent manner. Overexpression of miR-126-5p facilitated cell viability, while reduced cell apoptosis and inflammatory responses induced by MPP+ treatment. Moreover, SP1 was a target of miR-126-5p and could be negatively regulated by miR-126-5p. Overexpression of SP1 could reverse the effects of miR-126-5p on MPP+-administrated cells. CONCLUSION: Our results suggested that miR-126-5p attenuated the neurotoxicity induced by MPP+ in vitro through targeting SP1 (Graphical abstract), which further enhanced our understanding of the pathological mechanism of PD.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Risk factors for ophthalmic artery stenosis and occlusion in patients with retinoblastoma treated with intra-arterial chemotherapy.

PURPOSE: To explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma. DESIGN: Retrospective, single centre case-control study. METHODS: The study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter. RESULTS: 346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients' age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion. CONCLUSIONS: The OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

[Clinical characteristics and genetic analysis of an ethnic Han Chinese child with Keppen-Lubinsky syndrome due to a de novo KCNJ6 mutation].

OBJECTIVE: To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS). METHODS: Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel. CONCLUSION: The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.