Population pharmacokinetic analysis for dose regimen optimization of vancomycin in Southern Chinese children.

Changes in physiological factors may result in large pharmacokinetic variability of vancomycin in pediatric patients, thereby leading to either supratherapeutic or subtherapeutic exposure and potentially affecting clinical outcomes. This study set out to characterize the disposition of vancomycin, quantify the exposure target and establish an optimal dosage regimen among the Southern Chinese pediatric population. Routine therapeutic drug monitoring data of 453 patients were available. We performed a retrospective population pharmacokinetic analysis of hospitalized children prescribed intravenous vancomycin using NONMEM® software. A one-compartment PPK model of vancomycin with body weight and renal functions as covariates based on a cutoff of 2 years old children was proposed in this study. Both internal and external validation showing acceptable and robust predictive performance of the model to estimate PK parameters. The value of area under the curve over 24 h to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 260 was a significant predictor for therapeutic efficacy. Monte Carlo simulations served as a model-informed precision dosing approach and suggested that different optimal dose regimens in various scenarios should be considered rather than flat dosing. The evaluation of vancomycin exposure-efficacy relationship indicated that lower target level of AUC0-24/MIC may be needed to achieve clinical effectiveness in children, which was used to derive the recommended dosing regimen. Further prospective studies will be needed to corroborate and elucidate these results.

A data analysis framework for combining multiple batches increases the power of isobaric proteomics experiments.

We present a framework for the analysis of multiplexed mass spectrometry proteomics data that reduces estimation error when combining multiple isobaric batches. Variations in the number and quality of observations have long complicated the analysis of isobaric proteomics data. Here we show that the power to detect statistical associations is substantially improved by utilizing models that directly account for known sources of variation in the number and quality of observations that occur across batches.In a multibatch benchmarking experiment, our open-source software (msTrawler) increases the power to detect changes, especially in the range of less than twofold changes, while simultaneously increasing quantitative proteome coverage by utilizing more low-signal observations. Further analyses of previously published multiplexed datasets of 4 and 23 batches highlight both increased power and the ability to navigate complex missing data patterns without relying on unverifiable imputations or discarding reliable measurements.

Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing.

Background: SHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide. Methods: In this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants. Results: Two novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM_012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM_012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions. Conclusion: We identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2-related disorders.

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

SCN1A Polymorphisms and Haplotypes Are Associated With Valproic Acid Treatment Outcomes in Chinese Children With Epilepsy.

BACKGROUND: Sodium channel genes, especially SCN1A, were reported to play an important role in the treatment outcomes of antiseizure medications. The aim of this study was to explore the association of SCN1A polymorphisms with efficacy and adverse drug reactions (ADRs) related to valproic acid (VPA) among Chinese children with epilepsy. METHODS: A total of 126 children with epilepsy treated with VPA for at least 12 months were enrolled in this study. Three single nucleotide polymorphisms (SNPs) of SCN1A including rs2298771, rs10167228, and rs3812718 were genotyped using Sequenom MassArray system. Bioinformatics tools were used to explore the potential targets and pathways of SCN1A in VPA-related ADRs. RESULTS: The three SNPs in this study were found to be closely associated with treatment outcomes for VPA. Carriers of SCN1A rs3812718 TT genotype tended to be seizure-free with VPA treatment (P = 0.007). AA genotype of rs10167228 and TT genotype of rs2298771 might be protective factors for weight gain induced by VPA, whereas TA genotype of rs10167228 and CT genotype of rs2298771 increased the risk. TAT haplotype carriers were found to respond better to VPA treatment (P = 0.017), whereas CTC haplotype might be a risk factor for VPA-induced weight gain (P = 0.035). Bioinformatics analysis suggested that SCN1A might play a role in VPA-induced weight gain by regulating gated channel activity and GABAergic synapse pathway. CONCLUSION: This study revealed that SCN1A rs2298771, rs10167228, and rs3812718 polymorphisms and haplotypes might affect the treatment outcomes of VPA in Chinese children with epilepsy.

Phosphorus limitation induced by nitrogen addition changed soil microbial community structure in a subtropical Pinus taiwanensis forest.

Soil microorganisms play an important role in the biogeochemical cycles of terrestrial ecosystems. How-ever, it is still unclear how the amount and duration of nitrogen (N) addition affect soil microbial community structure and whether there is a correlation between the changes in microbial community structure and their nutrient limi-tation status. In this study, we conducted an N addition experiment in a subtropical Pinus taiwanensis forest to simulate N deposition with three treatments: control (CK, 0 kg N·hm-2·a-1), low N (LN, 40 kg N·hm-2·a-1), and high N (HN, 80 kg N·hm-2·a-1). Basic soil physicochemical properties, phospholipid fatty acids content, and carbon (C), N and phosphorus (P) acquisition enzyme activities were measured after one and three years of N addition. The relative nutrient limitation status of soil microorganisms was analyzed using ecological enzyme stoichiometry. The results showed that one-year N addition did not affect soil microbial community structure. Three-year LN treatment significantly increased the contents of Gram-positive bacteria (G+), Gram-negative bacteria (G-), actinomycetes (ACT), and total phospholipid fatty acids (TPLFA), whereas three-year HN treatment did not significantly affect soil microbial community, indicating that bacteria and ACT might be more sensitive to N addition. Nitrogen addition exacerbated soil C and P limitation. Phosphorus limitation was the optimal explanatory factor for the changes in soil microbial community structure. It suggested that P limitation induced by N addition might be more beneficial for the growth of certain oligotrophic bacteria (e.g. G+) and the microorganisms participating in the P cycling (e.g. ACT), with consequences on soil microbial community structure of subtropical Pinus taiwanensis forest.

An Automated, Home-Cage, Video Monitoring-based Mouse Frailty Index Detects Age-associated Morbidity in C57BL/6 and Diversity Outbred Mice.

Frailty indexes (FIs) provide quantitative measurements of nonspecific health decline and are particularly useful as longitudinal monitors of morbidity in aging studies. For mouse studies, frailty assessments can be taken noninvasively, but they require handling and direct observation that is labor-intensive to the scientist and stress inducing to the animal. Here, we implement, evaluate, and provide a refined digital FI composed entirely of computational analyses of home-cage video and compare it to manually obtained frailty scores in both C57BL/6 and genetically heterogeneous Diversity Outbred mice. We show that the frailty scores assigned by our digital index correlate with both manually obtained frailty scores and chronological age. Thus, we provide an automated tool for frailty assessment that can be collected reproducibly, at scale, without substantial labor cost.

Characteristics of Visual Fixation in Chinese Children with Autism During Face-to-Face Conversations.

Few eye tracking studies have examined how people with autism spectrum disorder (ASD) visually attend during live interpersonal interaction, and none with the Chinese population. This study used an eye tracker to record the gaze behavior in 20 Chinese children with ASD and 23 children with typical development (TD) when they were engaged in a structured conversation. Results demonstrated that children with ASD looked significantly less at the interlocutor's mouth and whole-face, and more at background. Additionally, gaze behavior was found to vary with the conversational topic. Given the great variability in eye tracking findings in existing literature, future explorations might consider investigating how fundamental factors (i.e., participant's characteristics, tasks, and context) influence the gaze behavior in people with ASD.

Pharmacogenetics-based population pharmacokinetic analysis and dose optimization of valproic acid in Chinese southern children with epilepsy: Effect of ABCB1 gene polymorphism.

Objective: The aim of this study was to establish a population pharmacokinetic (PPK) model of valproic acid (VPA) in pediatric patients with epilepsy in southern China, and provide guidance for individualized medication of VPA therapy. Methods: A total of 376 VPA steady-state trough concentrations were collected from 103 epileptic pediatric patients. The PPK parameter values for VPA were calculated by using the nonlinear mixed-effects modeling (NONMEM) method, and a one-compartment model with first-order absorption and elimination processes was applied. Covariates included demographic information, concomitant medications and selected gene polymorphisms. Goodness-of-fit (GOF), bootstrap analysis, and visual predictive check (VPC) were used for model evaluation. In addition, we used Monte Carlo simulations to propose dose recommendations for different subgroup patients. Results: A significant effect of the patient age and ABCB1 genotypes was observed on the VPA oral clearance (CL/F) in the final PPK model. Compared with patients with the ABCB1 rs3789243 AA genotype, CL/F in patients with GG and AG genotypes was increased by 8% and reduced by 4.7%, respectively. The GOF plots indicated the satisfactory predictive performance of the final model, and the evaluation by bootstrap and VPC showed that a stable model had been developed. A table of individualized dosing regimens involving age and ABCB1 genotype was constructed based on the final PPK model. Conclusion: This study quantitatively investigated the effects of patient age and ABCB1 rs3789243 variants on the pharmacokinetic variability of VPA. The PPK models could be beneficial to individual dose optimization in epileptic children on VPA therapy.

Triple-threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL-lpr mice.

Systemic lupus erythematosus is a common autoimmune inflammatory disease which is associated with increases in autoantibodies and immune complexes that deposit in the kidney. The MRL-lpr mouse is a common mouse model used for the study of lupus and immune complex glomerulonephritis but very little is known about the plasma proteome changes in this model. We performed in-depth quantitative proteome profiling on MRL-lpr and control (strain MpJ) mice to investigate the changes in the proteome, immunoglobulins and their glycoproteome as well as protein and immune complexes. Methodologies used included immunohistochemistry, immunoglobulin isotyping, multiplexed proteome profiling, immunoglobulin immunoprecipitation with glycoproteome profiling, and size exclusion chromatography (SEC) profiling to enable a comprehensive proteome profiling of proteins and protein complexes. We also used a novel native multiplexed plasma proteome profiling (NativeMP3) method that relies on native enrichment of plasma proteins enabling ultra-deep single shot profiling where we identified 922 plasma proteins at 1% false discovery rate (FDR) in a single shot mass spectrometry run. We observed many large plasma protein differences between the MRL-lpr and control strain including differences in the immunoglobulins, immunoglobulins against specific antigens, chemokines, and proteases as well as changes in protein complexes such as the immunoproteasome.

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Soil phosphatases are important in the mineralization of organophosphates and in the phosphorus (P) cycle. The kinetic mechanisms of phosphatases in response to nitrogen (N) deposition remain unclear. We carried out a field experiment with four different concentrations of N: 0 g N·hm-2·a-1(control), 20 g N·hm-2·a-1(low N), 40 g N·hm-2·a-1(medium N), and 80 g N·hm-2·a-1(high N) in a subtropical Moso bamboo forest. Soil samples were then collected from 0 to 15 cm depth, after 3, 5 and 7 years of N addition. We analyzed soil chemical properties and microbial biomass. Acid phosphatase (ACP) was investigated on the basis of maximum reaction velocity (Vm), Michaelis constant (Km), and catalytic efficiency (Ka). Results showed that N addition significantly decreased soil dissolved organic carbon (DOC), available phosphorus, and organophosphate content, but significantly increased soil ammonium, nitrate-N content, and Vm. There was a significant relationship between Vm and the concentrations of available phosphorus, organophosphate, and soil DOC. In general, N addition substantially increased Ka, but did not affect Km. The Km value in the high N treatment group was higher than that in the control group after five years of N addition. Km was significantly negatively associated with both available phosphorus and organophosphate. Medium and high N treatments had stronger effects on the kinetic parameters of ACP than low N treatment. Results of variation partition analysis showed that changes in soil chemical properties, rather than microbial biomass, dominated changes in Vm(47%) and Km(33%). In summary, N addition significantly affected substrate availability in Moso bamboo forest soil and modulated soil P cycle by regulating ACP kinetic parameters (especially Vm). The study would improve the understanding of the mechanisms underlying soil microorganisms-regulated soil P cycle under N enrichment. These mechanisms would identify the important parameters for improving soil P cycling models under global change scenarios.

Shotgun and TMT-Labeled Proteomic Analysis of the Ovarian Proteins of an Insect Vector, Aedes aegypti (Diptera: Culicidae).

Aedes aegypti [Linnaeus in Hasselquist; yellow fever mosquito] transmits several viruses that infect millions of people each year, including Zika, dengue, yellow fever, chikungunya, and West Nile. Pathogen transmission occurs during blood feeding. Only the females blood feed as they require a bloodmeal for oogenesis; in the bloodmeal, holo-transferrin and hemoglobin provide the females with a high iron load. We are interested in the effects of the bloodmeal on the expression of iron-associated proteins in oogenesis. Previous data showed that following digestion of a bloodmeal, ovarian iron concentrations doubles by 72 hr. We have used shotgun proteomics to identify proteins expressed in Ae. aegypti ovaries at two oogenesis developmental stages following blood feeding, and tandem mass tag-labeling proteomics to quantify proteins expressed at one stage following feeding of a controlled iron diet. Our findings provide the first report of mosquito ovarian protein expression in early and late oogenesis. We identify proteins differentially expressed in the two oogenesis development stages. We establish that metal-associated proteins play an important role in Ae. aegypti oogenesis and we identify new candidate proteins that might be involved in mosquito iron metabolism. Finally, this work identified a unique second ferritin light chain subunit, the first reported in any species. The shotgun proteomic data are available via ProteomeXchange with identifier PXD005893, while the tandem mass tag-labeled proteomic data are available with identifier PXD028242.

AS3MT Polymorphism: A Risk Factor for Epilepsy Susceptibility and Adverse Drug Reactions to Valproic Acid and Oxcarbazepine Treatment in Children From South China.

Epilepsy is a common neurologic disorder characterized by intractable seizures, involving genetic factors. There is a need to develop reliable genetic markers to predict the risk of epilepsy and design effective therapies. Arsenite methyltransferase (AS3MT) catalyzes the biomethylation of arsenic and hence regulates arsenic metabolism. AS3MT variation has been linked to the progression of various diseases including schizophrenia and attention deficit or hyperactivity disorder. Whether genetic polymorphism of AS3MT contributes to epilepsy remains unclear. In this study, we investigated the association of AS3MT gene polymorphism with susceptibility to epilepsy in children from south China. We also explored the effect of AS3MT variation on the safety of antiepileptic drugs. Genotypic analysis for AS3MT rs7085104 was performed using samples from a Chinese cohort of 200 epileptic children and 244 healthy individuals. The results revealed a genetic association of AS3MT rs7085104 with susceptibility to pediatric epilepsy. Mutant homozygous GG genotype exhibited a lower susceptibility to childhood epilepsy than AA genotype. Carriers of AS3MT rs7085104 AA genotype exhibited a higher risk of digestive adverse drug reactions (dADRs) in children when treated with valproic acid (VPA) or oxcarbazepine (OXC). Additionally, bioinformatics analysis identified eight AS3MT target genes related to epilepsy and three AS3MT-associated genes in VPA-related dADRs. The effects of AS3MT on epilepsy might involve multiple targets including CNNM2, CACNB2, TRIM26, MTHFR, GSTM1, CYP17A1, NT5C2, and YBX3. This study reveals that AS3MT may be a new gene contributing to epileptogenesis. Hence, analysis of AS3MT polymorphisms will help to evaluate susceptibility to pediatric epilepsy and drug safety.

A Multi-Information Fusion Method for Gait Phase Classification in Lower Limb Rehabilitation Exoskeleton.

Gait phase classification is important for rehabilitation training in patients with lower extremity motor dysfunction. Classification accuracy of the gait phase also directly affects the effect and rehabilitation training cycle. In this article, a multiple information (multi-information) fusion method for gait phase classification in lower limb rehabilitation exoskeleton is proposed to improve the classification accuracy. The advantage of this method is that a multi-information acquisition system is constructed, and a variety of information directly related to gait movement is synchronously collected. Multi-information includes the surface electromyography (sEMG) signals of the human lower limb during the gait movement, the angle information of the knee joints, and the plantar pressure information. The acquired multi-information is processed and input into a modified convolutional neural network (CNN) model to classify the gait phase. The experiment of gait phase classification with multi-information is carried out under different speed conditions, and the experiment is analyzed to obtain higher accuracy. At the same time, the gait phase classification results of multi-information and single information are compared. The experimental results verify the effectiveness of the multi-information fusion method. In addition, the delay time of each sensor and model classification time is measured, which shows that the system has tremendous real-time performance.

CRISPR/Cas9-Mediated in vivo Genetic Correction in a Mouse Model of Hemophilia A.

Hemophilia A (HA), a common bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII), has long been considered an attractive target for gene therapy studies. However, full-length F8 cDNA cannot be packaged efficiently by adeno-associated virus (AAV) vectors. As the second most prevalent mutation causing severe HA, F8 intron 1 inversion (Inv1) is caused by an intrachromosomal recombination, leaving the majority of F8 (exons 2-26) untranscribed. In theory, the truncated gene could be rescued by integrating a promoter and the coding sequence of exon 1. To test this strategy in vivo, we generated an HA mouse model by deleting the promoter region and exon 1 of F8. Donor DNA and CRISPR/SaCas9 were packaged into AAV vectors and injected into HA mice intravenously. After treatment, F8 expression was restored and activated partial thromboplastin time (aPTT) was shortened. We also compared two liver-specific promoters and two types of integrating donor vectors. When an active promoter was used, all of the treated mice survived the tail-clip challenge. This is the first report of an in vivo gene repair strategy with the potential to treat a recurrent mutation in HA patients.

Genetic Polymorphism of GABRG2 rs211037 is Associated with Drug Response and Adverse Drug Reactions to Valproic Acid in Chinese Southern Children with Epilepsy.

BACKGROUND: Valproic acid (VPA) is recommended as a first-line treatment for children with epilepsy. GABRG2 polymorphism is found to be associated with epilepsy susceptibility and therapeutic response of anti-seizure medications (ASM); however, the role of GABRG2 in VPA treatment still remains unknown. OBJECTIVE: The purpose of this study was to explore the association of GABRG2 gene polymorphism with the drug response and adverse drug reactions (ADRs) related to VPA. METHODS: A retrospective study including 96 Chinese children with epilepsy treated by VPA was carried out. The ADRs were collected during VPA therapy and GABRG2 rs211037 in enrolled patients was genotyped using Sequenom MassArray system. A network pharmacological analysis involved protein-protein interaction and enrichment analysis was constructed to investigate the potential targets and pathways of GABRG2 on VPA-related ADRs. RESULTS: Among 96 patients, 41 individuals were defined as seizure together with 49 patients with seizure-free and 6 patients unclassified. Carriers of homozygote GABRG2 rs211037 CC genotype exhibited seizure-free to VPA (P = 0.042), whereas those with CT genotype showed seizure. Furthermore, CC genotype had predisposition to digestive ADRs (P = 0.037) but was a protective factor for VPA-associated weight gain (P = 0.013). Ten key genes related to digestive ADRs and weight gain induced by VPA were identified by network pharmacological analysis and mainly involved in "GABAergic synaptic signaling", "GABA receptor signaling", and "taste transduction" pathways/processes through enrichment analysis. CONCLUSION: This study revealed that GABRG2 variation exerted a predictable role in the efficacy and safety of VPA treatment for Chinese children with epilepsy.

Four new species of Panophrys (Anura, Megophryidae) from eastern China, with discussion on the recognition of Panophrys as a distinct genus.

The diversity of Panophrys horned toads is considered highly underestimated with a large number of undescribed cryptic species. In this work, we describe four Panophrys species from eastern China which were proposed as cryptic species by molecular data in previous study, additionally provide new information on the biogeography of these four species. Panophrys daiyunensis sp. nov. from southern Fujian, Panophrys daoji sp. nov. from eastern Zhejiang, Panophrys sanmingensis sp. nov. from the hilly area among Fujian, Jiangxi and Guangdong, and Panophrys tongboensis sp. nov. from northeastern Jiangxi, can be distinguished from all recognized congeners by a combination of morphological characteristics. The descriptions of these four new species take the recognized species of Panophrys to 51, which is the largest genus within the Asian horned toads subfamily Megophryinae. Considered as an appropriate arrangement for the Asian horned toads currently and applied in this study to describe the new species, the generic recognition of Panophrys is also discussed.

SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively. Sirt6 knockdown in AML12 cells aggravated APAP-induced hepatocyte death and oxidative stress, inhibited cell viability and proliferation, and downregulated CCNA1, CCND1 and CKD4 protein levels. Sirt6 knockdown significantly prevented APAP-induced NRF2 activation, reduced the transcriptional activities of GSTµ and NQO1 and the mRNA levels of Nrf2, Ho-1, Gstα and Gstµ. Furthermore, SIRT6 showed potential protein interaction with NRF2 as evidenced by co-immunoprecipitation (Co-IP) assay. Additionally, the protective effect of P53 against APAP-induced hepatocytes injury was Sirt6-dependent. The Sirt6 mRNA was significantly down-regulated in P53 -/- mice. P53 activated the transcriptional activity of SIRT6 and exerted interaction with SIRT6. Our results demonstrate that SIRT6 protects against APAP hepatotoxicity through alleviating oxidative stress and promoting hepatocyte proliferation, and provide new insights in the function of SIRT6 as a crucial docking molecule linking P53 and NRF2.

Clinical features of patients undergoing hemodialysis with COVID-19.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.

Genetic Polymorphism of ADORA2A Is Associated With the Risk of Epilepsy and Predisposition to Neurologic Comorbidity in Chinese Southern Children.

Epilepsy, a common disorder of the brain, exhibits a high morbidity rate in children. Childhood epilepsy (CE) is frequently comorbid with neurologic and developmental disorders, sharing underlying genetic factors. This study aimed to investigate the impact of ADORA2A, BDNF, and NTRK2 gene polymorphisms on the risk of childhood epilepsy and their associations with predisposition to epileptic comorbidities. A total of 444 children were enrolled in this study, and three single nucleotide polymorphisms, including ADORA2A rs2298383, BDNF rs6265, and NTRK2 rs1778929, were genotyped. The frequency distribution of genotypes was compared not only between CE patients and healthy children but also between CE patients with and without comorbidities. The results indicated that the carriers of ADORA2A rs2298383 TT genotype tended to have a lower risk of epilepsy (OR = 0.48, 95% CI = 0.30-0.76), while the CT genotype was related to a higher risk (OR = 1.56, 95% CI = 1.06-2.27). The ADORA2A rs2298383 CC genotype predisposed CE patients to comorbid neurologic disorders (OR = 2.76, 95% CI = 1.31-5.80). Genetic variations in BDNF rs6265 and NTRK2 rs1778929 had no significant association with CE and its comorbidities. Fourteen ADORA2A target genes related to epilepsy were identified by the protein-protein interaction analysis, which were mainly involved in the biological processes of "negative regulation of neuron death" and "purine nucleoside biosynthetic process" through the gene functional enrichment analysis. Our study revealed that the genetic polymorphism of ADORA2A rs2298383 was associated with CE risk and predisposition to neurologic comorbidity in children with epilepsy, and the involved mechanism might be related to the regulation of neuron death and purine nucleoside biosynthesis.