Novel Genetic Variants Distinguishing Myelin Oligodendrocyte Glycoprotein-IgG-Positive From Myelin Oligodendrocyte Glycoprotein-IgG-Negative Pediatric Acute Disseminated Encephalomyelitis in Northern China.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a common phenotype in children with myelin oligodendrocyte glycoprotein IgG (MOG-IgG)-associated disease. We aimed to identify novel genetic variants that distinguish children with MOG-IgG-positive ADEM (MOG-IgG+ ADEM) from children with MOG-IgG-negative ADEM (MOG-IgG- ADEM) using whole exome sequencing (WES) analysis. METHODS: We conducted a two-stage study design. First, we performed WES on five patients with MOG-IgG+ ADEM and five patients with MOG-IgG- ADEM. Following bioinformatics analysis, the candidate variant list was constructed. Second, 29 children with MOG-IgG+ ADEM and 27 children with MOG-IgG- ADEM, together with discovery cohort, were genotyped to identify the novel variants. RESULTS: WES resulted in 33,999 variants, and 5388 nonsynonymous variants were selected for downstream analysis. In total, 118 protein-affecting variants that were significantly different between the two groups were identified. Together with the five variants extracted from the literature, 49 variants were selected as the candidate variant list for genotyping in the replication cohort. Finally, we identified three variants: rs11171951 in NACα, rs231775 in CTLA4, and rs11171951 in GOLGA5, which were significantly different between MOG-IgG+ ADEM and MOG-IgG- ADEM. Only rs12440118 in NACα remained significant after Bonferroni correction for multiple testing (Padj < 0.001). CONCLUSIONS: We identified strong associations between NACα, CTLA4, and GOLGA5 variants and MOG-IgG+ ADEM in a Han Chinese population of Northern China, which may present novel genetic risk factor distinguishing patients with MOG-IgG+ ADEM from those with MOG-IgG- ADEM.

Whole exome sequencing approach for identification of the molecular etiology in pediatric patients with hematuria.

BACKGROUND: Hematuria is a common condition in clinical practice of pediatric patients. It is related to a wide spectrum of disorders and has high heterogeneity both clinically and genetically, which contributes to challenges of diagnosis and lead many pediatric patients with hematuria not to receive accurate diagnosis and early management. METHODS: In this single center study, 42 children with hematuria were included in Tianjin Children's Hospital between 2019 and 2020. We analyzed the clinical information and performed WES (Whole exome sequencing) for all cases. Then the classification of identified variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpreting sequence variants. For the fragment deletion, qPCR was performed to validate and confirm the inherited pattern. RESULTS: For the 42 patients, 16 cases had gross hematuria and 26 had microscopic hematuria. Molecular genetic causes were uncovered in 9 (21.4%) children, including 7 with Alport syndrome (AS), one with polycystic nephropathy and one with lipoprotein glomerulopathy. The genetic causes for other patients were not related with hematuria. CONCLUSIONS: WES is a rapid and effective way to evaluate patients with hematuria. The analysis of genotype-phenotype correlations of patients with AS indicated that severe variants were associated with early kidney failure. Secondary findings were not rare in Chinese children, thus the clinician should pay more attention to the clinical interpretation of sequencing results and properly interaction with patients and their family.

Interfacial polymerization mechanisms assisted flame retardancy process of low-flammable electrolytes on lithium anode.

Thermal runaway is a hazardous risk, occurring more readily in high-energy-density lithium-ion batteries (LIBs), which leads to a rapid temperature rise and even combustion or explosion when using flammable electrolyte systems. Flame retardants (FRs), such as trimethyl phosphate (TMPa) and triethyl phosphate (TEP), are commonly utilized due to their effective flame suppression, low toxicity, and excellent thermal stability. However, the lack of in-depth understanding of the flame retardancy mechanism and solid electrolyte interphase (SEI) formation process has made the development of functional electrolytes difficult at present. In this study, we clarified the flame retardancy and interfacial reaction mechanisms of low-flammable TMPa localized high-concentration electrolytes (LHCE) using hybrid ab initio and reactive force field (HAIR) schemes. Long-term HAIR simulation reveals that phosphorous radicals produced by the decomposition of TMPa capture carbon radicals, encouraging their polymerization into low-flammable oligomers, while fluorine-containing solvents in the electrolyte capture hydrogen radicals and produce nonflammable hydrofluoric acid (HF). This synergistic flame retardancy mechanism provides essential atomic-level insights for the rational design of high-safety electrolytes in the future.

Diversity and Antimicrobial Activity of Intestinal Fungi from Three Species of Coral Reef Fish.

Although intestinal microbiota play crucial roles in fish digestion and health, little is known about intestinal fungi in fish. This study investigated the intestinal fungal diversity of three coral reef fish (Lates calcarifer, Trachinotus blochii, and Lutjanus argentimaculatus) from the South China Sea using a culturable method. A total of 387 isolates were recovered and identified by sequencing their internal transcribed spacer sequences, belonging to 29 known fungal species. The similarity of fungal communities in the intestines of the three fish verified that the fungal colonization might be influenced by their surrounding environments. Furthermore, the fungal communities in different intestines of some fish were significantly different, and the number of yeasts in the hindgut was less than that in fore- and mid-intestines, suggesting that the distribution of fungi in fishes' intestines may be related to the physiological functions of various intestinal segments. In addition, 51.4% of tested fungal isolates exhibited antimicrobial activity against at least one marine pathogenic microorganism. Notably, isolate Aureobasidium pullulans SCAU243 exhibited strong antifungal activity against Aspergillus versicolor, and isolate Schizophyllum commune SCAU255 displayed extensive antimicrobial activity against four marine pathogenic microorganisms. This study contributed to our understanding of intestinal fungi in coral reef fish and further increased the library of fungi available for natural bioactive product screening.

Genomic insights into secondary metabolites of pharmaceutical utility for Hyphococcus flavus MCCC 1K03223T, isolated from bathypelagic seawater.

During an attempt to screen secondary metabolites of pharmaceutical utility, we sequenced the complete genome of type strain of a novel marine bacterial genus, named genus Hyphococcus. The type strain, Hyphococcus flavus MCCC 1K03223T, was isolated from bathypelagic seawater of South China Sea at a depth of 2500 m. The complete genome of strain MCCC 1K03223T is composed of a circular chromosome of 3,472,649 bp with a mean G + C content of 54.8%. Functional genomic analysis showed that this genome encodes five biosynthetic gene clusters, which were annotated to synthesize medicinally important secondary metabolites. Secondary metabolites annotated include ectoine which acts cytoprotection, ravidomycin which is an antitumor antibiotic and three other different metabolites of terpene type. The secondary metabolic potentials of H. flavus revealed in this study provide more evidences on mining bioactive substances from marine bathypelagic microorganisms.

Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects.

BACKGROUND: Dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been approved for improving glycemic control and reducing the risk of cardiovascular (CV) adverse events. This study compared the pharmacokinetic (PK) profiles, safety, and immunogenicity of LY05008, a biosimilar candidate, to a licensed product dulaglutide in healthy Chinese male subjects. RESEARCH DESIGN AND METHODS: In this double-blind, open-label, parallel-group study, healthy Chinese male subjects were randomized 1:1 to receive either LY05008 or dulaglutide subcutaneously. Primary study endpoints were PK parameters such as the area under the concentration-time curve (AUC) from time zero to infinity (AUC0 - ∞), AUC from time zero to the last quantifiable concentration (AUC0-t), and maximum serum concentration (Cmax). Safety and immunogenicity profiles were also included for data analysis. RESULTS: 82 subjects were randomized to receive LY05008 (n = 41) or dulaglutide (n = 41). The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC0 - ∞, AUC0-t and Cmax of LY05008 to dulaglutide were all within the bioequivalence limits of 80%-125%. Other PK parameters, safety, and immunogenicity profiles were comparable across the two treatment groups. CONCLUSION: This study demonstrated PK similarity of LY05008, a dulaglutide biosimilar, to dulaglutide in healthy Chinese male subjects, with comparable safety and immunogenicity data. TRIAL REGISTRATION: The trial is registered at the Chinese Clinical Trial Registry (Identifier No. ChiCTR2200066519).

Prader-Willi syndrome patient with atypical phenotypes caused by mosaic deletion in the paternal 15q11-q13 region: a case report.

BACKGROUND: Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by the loss of paternally expressed genes in the human chromosome region 15q11.2-q13. It is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity. Motor milestones and language development are delayed and most patients have intellectual disability. CASE PRESENTATION: Here we describe a rare PWS case caused by mosaic imprinting defect in the region 15q11.2-q13 of paternal origin. The proband was a male child with a clinical presentation of global developmental delay and hypotonia with specific facial features. Karyotype of the child was noted as mosaic: 45XY,der(15)?t(15;21),-21[26]/46,XY[24]. Whole-exome sequencing (WES) identified a deletion of 22.7 Mb in size at chr15q11.2q21.1 region and a deletion of 2.1 Mb in size at chr21q22.3 region. The Methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA) of the 15q11.2-q13 region showed that the loading ratio of methylated alleles was 70% and that of unmethylated alleles was 30%(50% normal), which confirmed that the loss of mosaic imprinted defects in the paternal allele led to the diagnosis of PWS. CONCLUSIONS: We propose that complete clinical criteria for PWS should not be considered sensitive in diagnosing partial atypical PWS due to mosaic imprinting defects. In contrast, clinical suspicion based on less restrictive criteria followed by multiple techniques is a more powerful approach.

Case report: Altered pre-mRNA splicing caused by intronic variant c.1499 + 1G > A in the SLC4A4 gene.

Proximal renal tubular acidosis (pRTA) with ocular abnormalities is an autosomal recessive disease caused by variants in the Solute Carrier Family 4 Member 4 (SLC4A4) gene. Patients present with metabolic acidosis and low plasma bicarbonate concentration (3∼17 mmol/L). In addition, they are often accompanied by ocular abnormalities, intellectual disability, and growth retardation. The patient underwent whole exome sequencing (WES) and bioinformatics analysis of variant pathogenicity in this study. Then, a minigene assay was conducted to analyze the splicing site variant further. Compound heterozygous variants in the SLC4A4 gene (NM_003759.3), c.145C > T (p.Arg49*) and c.1499 + 1G > A, were detected by WES. The minigene assay showed an mRNA splicing aberration caused by the c.1499 + 1G > A variant. Compared with the wild type, the mutant type caused 4-base insertion between exons 10 and 11 of SLC4A4 after expression in HEK293 cells. In conclusion, the c.1499 + 1G > A variant in the SLC4A4 gene may be one of the genetic causes in the patient. Moreover, our study provides the foundation for future gene therapy of such pathogenic variants.

Epidemiological Features of Klebsiella pneumoniae Infection in the Hepatobiliary System of Patients in Yantai, China, Based on Clinical and Genetic Analyses.

Purpose: To investigate the epidemiological features of Klebsiella pneumoniae infection of the hepatobiliary system of patients in Yantai, China. Methods: This retrospective study was conducted from January to December 2019 in Yantai Yuhuangding Hospital. Patients for whom K. pneumoniae was isolated from the hepatobiliary system were considered for inclusion. The clinical features and genetic analyses were conducted to explore the epidemiological characteristics. Results: A total of 88 cases were enrolled, including 69 cases of hypervirulent K. pneumoniae (hvKP) and 19 cases of classical K. pneumoniae (cKP). Community-acquired infections, fever, liver abscess, and C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher, while biliary tract disease was lower in the hvKP group compared with the cKP group. Among the 69 hvKP infections, 61 developed a liver abscess. Community-acquired infections, fever, and CRP and PCT levels were higher, whereas biliary tract disease and malignancy were lower in the liver abscess group compared with the non-liver abscess group. All strains were susceptible to the majority of antibiotics tested. All hvKP strains possessed the bla SHV, oqxA, oqxB and fosA resistance genes. K1 and K2 accounted for 78% of hvKP strains. K1 strains belonged to sequence types ST23 and ST700, whereas K2 strains belonged to ST65, ST86 and ST5212. K1 isolates possessed the most virulence determinants, followed by K2 and non-K1/K2 isolates. K2 isolates lacked the allS gene, which was rare in non K1/K2 isolates, but present in most K1 isolates. The mceG gene was only detected in K1 isolates. AllS and virulence determinants were significantly more prevalent in the liver abscess group than in the non-liver abscess group. Conclusion: The prevalence of hvKP among K. pneumoniae infections of the hepatobiliary system is high in Yantai, China. Greater vigilance of hvKP infection is required in clinical and microbiological laboratories.

Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum ß-Lactamases as Well as Omp Mutation.

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla SHV-1 only, and four harbored bla SHV-1 and bla TEM-1B. Two Escherichia coli strains carried bla TEM-1B only, while two Klebsiella oxytoca isolates harbored bla OXY-1-3 and bla OXY-1-1, respectively. No mutation in the ß-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum ß-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae. Antibiotic susceptibility tests Antibiotics Breakpoint, (µg/ml) Klebsiella pneumoniae Escherichia cou Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO ≤1≥4 ≤0.5 ≤0.5 ≤0.5 ≤0.5 1 ≤0.5 1 ≤0.5 ≤0.5 1 1 CAZ 4 ≥16 1 2 1 4 4 4 4 2 4 1 1 FEP ≤2 216 1 1 0.25 1 2 2 2 0.5 2 1 1 AMC ≤8 ≥32 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 CSL ≤16 ≥64 64 64 64 64 ≥128 128 ≥128 64 128 128 ≥128 TZP ≤16 ≥128 ≥256 ≥256 ≥256 ≥256 2256 2256 ≥256 ≥256 ≥256 ≥256 ≥256 FPT ≤2 ≥16 1 0.5 0.06 0.125 2 1 2 0.25 1 0.125 0.25 FPZ ≤2 216 0.25 0.25 0.06 0.125 0.25 0.25 1 0.125 0.25 0.125 0.125 CZA ≤8 216 1 0.5 0.25 0.25 1 0.25 1 0.5 0.5 0.5 0.25 CZT ≤2 28 2 1 0.5 1 2 2 2 1 1 2 2 CROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results Number Strain ST p-Lactamase gene Promoter sequence mutation Omp mutation El Kpn 45 blaSHV-1, blaTEM-lB none OmpK36, OmpK3 7 E3 Kpn 45 blaSHV-1, blaTEM-lB none OmpK36. OmpK3 7 E4 Kpn 2854 blaSHV-1 none OmpK36, OmpK3 7 E7 Kpn 2358 blaSHV-1 - blaTEM-lB none OmpK36, OmpK3 7 E9 Kpn 2358 blaSHV-1. blaTEM-lB none OmpK36. OmpK3 7 E10 Kpn 18 9 blaSHV-1 none OmpK36. OmpK3 7 Ell Kpn 45 blaSHV-1 none OmpK36, OmpK3 7 E6 Eco 88 blaTEM-lB none none ES Eco 409 blaTEM-1B none none E2 Kox 194 blaOXY-1-3 none OmpK36 mutations. OmpK35 and OmpK 37 deficiency E5 Kox 11 blaOXY-1-1 none no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found.

Prevalence of Hypertension and 10-Year Cardiovascular Disease Risk Among Older Adults Living in Quanzhou, A Coastal Region of Southeast China.

Objective: This study aims to analyze the prevalence of hypertension and 10-year cardiovascular disease (CVD) risk among older adults living in a coastal region of southeast China. Methods: A population-based cross-sectional survey of 2018 adults was conducted on 60-98-year-old residents in Quanzhou from September 2016 to March 2018 using multistage stratified cluster random sampling. The 10-year CVD risk was estimated by applying the Chinese model recommended by the Chinese guidelines for CVD prevention. Results: The overall prevalence of hypertension, prehypertension, and normotension among older adults in Quanzhou was 29.0%, 18.7%, and 52.3%, respectively. The percentage of participants with low, moderate, and high 10-year CVD risk was 49.7%, 36.8%, and 13.5%, respectively. Older age, low salt awareness, and low levels of physical activity were significantly correlated with hypertension. The 10-year CVD risk was higher for men than women and increased with age. Higher blood pressure was associated with a greater 10-year CVD risk. Conclusion: More than half of the older adults in Quanzhou surveyed by this study were normotensive, and approximately half the participants had a moderate or high 10-year CVD risk. We recommend the implementation of regionally targeted interventions, such as screening of blood pressure and other risk factors, to reduce blood pressure and CVD risk in Chinese populations.

Molecular cloning, expressional analyses and functional identification of TRAIL in tilapia, Oreochromis niloticus.

The tumour necrosis factor superfamily (TNFSF) plays critical roles in tumour apoptosis, tissue morphogenesis and lineage determination. TNFSF10 (TRAIL or Apol-2) belongs to the tumour necrosis factor (TNF) cytokine family and induces rapid apoptosis in a wide variety of tumour cell lines upon binding to death-inducing signalling receptors. In this study, we identified TNFSF10 from Nile tilapia (Oreochromis niloticus) and found it was most closely related to Japanese pufferfish (Takifugu rubripes) TNFSF10. Amino acid identity between tilapia TNFSF10 and mandarin fish (Siniperca chuatsi) TRAIL was 69.2%. The highest expression of TNFSF10 mRNA was observed in the liver. In vitro studies showed that the mRNA expression of TNFSF10 was significantly stimulated by LPS in head kidney leucocytes, but remarkably inhibited by Poly I:C in spleen leucocytes. In vivo studies showed Streptococcus agalactiae infection significantly induced the mRNA expression of TNFSF10 in both the head kidney and spleen. The soluble recombinant protein Trx-TNFSF10 could induce cytotoxicity and apoptosis in HeLa cells with cycloheximide as a promoter. Taken together, these results in this study indicate that TNFSF10 may play important roles in the immune system of Nile tilapia.

Molecular epidemiology of norovirus infections in children with acute gastroenteritis in 2017-2019 in Tianjin, China.

Norovirus (NoV) is the leading cause of acute gastroenteritis (AGE) worldwide. Globally, the GII.4 Sydney 2012 strain has predominated since 2012, although GII.4 variant strains have caused AGE outbreaks in China. Recent patterns of NoV genotype distributions in 6011 children with AGE in Tianjin, China were investigated. NoV was detected using real-time reverse-transcriptase polymerase chain reaction and sequencing of partial sequences of the viral capsid gene. NoV genotypes were determined, and phylogenetic analysis was conducted. Epidemiological and clinical data were compared between children infected with different NoV genotypes. NoV was detected in 27.6% of the specimens tested. GII.4 strains comprised 49.4% infections, followed by GII.3 at 39.9%. Genotypes GII.2, GII.13, GII.17, GII.1, GII.6, and GII.14 were also detected. NoV was detected during most of the year, with a peak season of cases in the winter. Diarrhea, vomiting, fever, abdominal pain, and dehydration were present in patients with NoV infection. The main genotypes were GII.4 and GII.3, with a slight increase in GII.2, beginning in March 2017. Among the GII.4 strains, GII.4 Sydney 2012 was the only epidemic strain in Tianjin. Patients with GII.4 genotypes were more likely to present with diarrhea and vomiting than those with GII.3. Children with GII. Others were prone to suffered from dehydration and abdominal pain than those with GII.3. NoV GII has become the main cause of viral AGE in Tianjin, China. The predominant genotypes of NoV were GII.4 and GII.3. Identification of emerging genotypes is crucial for the prevention and control of NoV-caused AGE.

Molecular epidemiology and genetic diversity of norovirus among hospitalized children with acute gastroenteritis in Tianjin, China, 2018-2020.

BACKGROUND: Norovirus (NoV) is a major cause of viral acute gastroenteritis (AGE) in children worldwide. Epidemiological analysis with respect to the virus strains is limited in China. This study aimed to investigate the prevalence, patterns, and molecular characteristics of NoV infection among children with AGE in China. METHODS: A total 4848 stool samples were collected from children who were admitted with AGE in Tianjin Children's Hospital from August 2018 to July 2020. NoV was preliminarily detected using real-time reverse transcription polymerase chain reaction (RT-PCR). Partial sequences of the RNA-dependent RNA polymerase (RdRp) and capsid genes of positive samples were amplified by conventional RT-PCR and then sequenced. The NoV genotype was determined by online Norovirus Typing Tool Version 2.0, and phylogenetic analysis was conducted using MEGA 6.0. RESULTS: The prevalence of NoV was 26.4% (1280/4848). NoV was detected in all age groups, with the 7-12 months group having the highest detection rate (655/2014, 32.5%). NoV was detected during most part of the year with higher frequency in winter than other seasons. Based on the genetic analysis of RdRp, GII. Pe was the most predominant genotype detected at 70.7% (381/539) followed by GII.P12 at 25.4% (137/539). GII.4 was the most predominant capsid genotype detected at 65.3% (338/518) followed by GII.3 at 26.8% (139/518). Based on the genetic analysis of RdRp and capsid sequences, the strains were clustered into 10 RdRp-capsid genotypes: GII.Pe-GII.4 Sydney 2012 (65.5%), GII.P12-GII.3 (27.2%), GII.P16-GII.2 (1.8%), GII.P12-GII.2 (0.2%), GII.P17-GII.17 (1.1%), GII.Pe-GII.3 (1.8%), GII.Pe-GII.2 (1.1%), GII.Pe-GII.1 (0.4%), GII.16-GII.4 Sydney 2012 (0.7%), and GII.P7-GII.6 (0.2%). The predominant NoV genotypes changed from GII.Pe-GII.4 Sydney 2012 and GII.P12-GII.3 between August 2018 and July 2019 to GII.Pe-GII.4 Sydney 2012 and GII.P16-GII.2 between August 2019 and July 2020. The patients with GII.Pe-GII.4 Sydney 2012 genotype were more likely to suffer from vomiting symptom than those with GII.P12-GII.3. CONCLUSIONS: NoV is an important pathogen responsible for viral AGE among children in China. GII.Pe-GII.4 Sydney 2012 and GII.P12-GII.3 were major recombinant genotypes. Knowledge of circulating genotypes and seasonal trends is of great importance for disease prevention and surveillance.

Disseminated Trichosporon asahii infection presenting as eosinophilia in an immunocompetent patient: A case report.

Trichosporon are naturally found in external environments and are a part of the normal flora of the human skin, respiratory tract, and gastrointestinal tract. Disseminated Trichosporon infection occurs sporadically in patients with immunodeficiency, and is mainly manifested as blood, urine, catheter, and thorax/peritoneum infections, rarely as lymphatic, liver and spleen infections. Elevated blood eosinophil granulocyte from Trichosporon infection have rarely been reported. Here, we report a rare Case of eosinophilia associated with lymphatic and liver and spleen infections due to Trichosporon asahii in an immunocompetent patient. No reports of eosinophilia from Trichosporon infections other than lung, to our knowledge, have been published.

Involvement of SAMHD1 in dNTP homeostasis and the maintenance of genomic integrity and oncotherapy (Review).

Sterile alpha motif and histidine/aspartic acid domain­containing protein 1 (SAMHD1), the only deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, plays a crucial role in regulating the dynamic balance and ratio of cellular dNTP pools. Furthermore, SAMHD1 has been reported to be involved in the pathological process of several diseases. Homozygous SAMHD1 mutations have been identified in immune system disorders, such as autoimmune disease Aicardi­Goutières syndrome (AGS), whose primary pathogenesis is associated with the abnormal accumulation and disproportion of dNTPs. SAMHD1 is also considered to be an intrinsic virus­restriction factor by suppressing the viral infection process, including reverse transcription, replication, packaging and transmission. In addition, SAMHD1 has been shown to promote genome integrity during homologous recombination following DNA damage, thus being considered a promising candidate for oncotherapy applications. The present review summarizes the molecular mechanisms of SAMHD1 regarding the regulation of dNTP homeostasis and DNA damage response. Additionally, its potential effects on tumorigenesis and oncotherapy are reported.

Species Distribution And Antibiotic Susceptibility Of Nocardia Isolates From Yantai, China.

PURPOSE: This study aimed to investigate the species distributions and drug sensitivities among 19 strains of Nocardia isolated from Yantai, China, from 2017 to 2019. PATIENTS AND METHODS: Definitive species identification was performed by sequencing a fragment of the 16S rRNA gene (1480 bp) and by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The susceptibilities of the isolates to 15 commonly-used antibiotics were tested using the microbroth dilution method. RESULTS: Among the 19 Nocardia isolates, five species were confirmed. Seventeen of the 19 Nocardia spp. strains were identified consistently by the two methods, while two isolates of N. cyriacigeorgica were misidentified as N. otitidiscaviarum by MALDI-TOF MS. N. farcinica was the most common species (8/19), followed by N. cyriacigeorgica (6/19), N. otitidiscaviarum (2/19), N. brasiliensis (2/19), and N. nova (1/19). All isolates were susceptible to trimethoprim-sulfamethoxazole and amikacin, followed by linezolid and tigecycline (94.7% susceptibility rates). The sensitivity and minimum inhibitory concentration patterns for ciprofloxacin, moxifloxacin, clarithromycin, and tobramycin were significantly correlated with the species. CONCLUSION: These results regarding the distribution and antibiotic resistance features of Nocardia species further our understanding of the diversity of Nocardia species circulating in Yantai, China, and thus support the use of more accurate empirical treatments.

[Application of radial-lateral forearm free perforator flap on repairing of soft tissue defects in finger].

OBJECTIVE: To investigate the effectiveness of radial-lateral forearm free perforator flap on repairing of soft tissue defects in the finger. METHODS: Between January 2017 and May 2018, 26 cases of finger skin defects were treated with radial-lateral forearm free perforator flap based on the radial branch of the posterior interosseus artery. There were 21 males and 5 females, with an average age of 26.6 years (range, 19-56 years). The cause of injury included the cutting injury in 16 cases and crush injury in 10 cases. The interval between injury and admission was 30 minutes to 4 hours (mean, 1.5 hours). The injury located at thumb in 6 cases, index finger in 8 cases, middle finger in 6 cases, ring finger in 3 cases, and little finger in 3 cases; and at the dorsum of finger in 6 cases, the lateral side in 6 cases, and the palm in 14 cases. All wounds were accompanied with the tendon and bone exposures, and phalangeal fractures occurred in 10 cases. The size of the defects ranged from 2.0 cm×1.0 cm to 4.0 cm×2.5 cm. And the size of the flap ranged from 2.5 cm×1.5 cm to 4.5 cm×3.0 cm. All wounds at donor sites were sutured directly. RESULTS: All the 26 cases were followed up 4-12 months (mean, 7 months). The 24 flaps survived uneventfully after operation, and the wounds healed by first intention. Partial necrosis occurred at the distal part in 2 flaps, and secondary healing achieved after debridement and dressing. All incisions at donor sites healed by first intention. The appearance and texture of all flaps were satisfactory. The two-point discrimination of the flaps was 5-10 mm (mean, 8 mm) at 4 months after operation. Sensory of the flaps was grade S 3. Only linear scar was noted at the donor site. CONCLUSION: The radial-lateral forearm free perforator flap in repairing of the soft tissues in finger can shorten the disease duration, reduce the damage of the donor site, and improve the patients' quality of life.

Proteomic Study of a Parkinson's Disease Model of Undifferentiated SH-SY5Y Cells Induced by a Proteasome Inhibitor.

Parkinson's disease (PD) is one of the most common nervous system degenerative diseases. However, the etiology of this disease remains elusive. Here, a proteasome inhibitor (PSI)-induced undifferentiated SH-SY5Y PD model was established to analyze protein alterations through proteomic study. METHODS: Cultured undifferentiated SH-SY5Y cells were divided into a control group and a group treated with 2.5 µM PSI (PSI-treated group). An methyl thiazolyl tetrazolium (MTT) assay was applied to detect cell viability. Acridine orange/ethidium bromide (AO/EB), α-synuclein immunofluorescence and hematoxylin and eosin (H&E) staining were applied to evaluate apoptosis and cytoplasmic inclusions, respectively. The protein spots that were significantly changed were separated, analyzed by 2D gel electrophoresis and DIGE De Cyder software, and subsequently identified by MALDI-TOF mass spectrometry and database searching. RESULTS: The results of the MTT assay showed that there was a time and dose dependent change in cell viability following incubation with PSI. After 24 h incubation, PSI resulted in early apoptosis, and cytoplasmic inclusions were found in the PSI-treated group through H&E staining and α-synuclein immunofluorescence. Thus, undifferentiated SH-SY5Y cells could be used as PD model following PSI-induced inhibition of proteasomal function. In total, 18 proteins were differentially expressed between the groups, 7 of which were up-regulated and 11 of which were down-regulated. Among them, 5 protein spots were identified as being involved in the ubiquitin proteasome pathway-induced PD process. CONCLUSIONS: Mitochondrial heat shock protein 75 (MTHSP75), phosphoglycerate dehydrogenase (PHGDH), laminin binding protein (LBP), tyrosine 3/tryptophan 5-monooxygenase activation protein (14-3-3ε) and YWHAZ protein (14-3-3ζ) are involved in mitochondrial dysfunction, serine synthesis, amyloid clearance, apoptosis process and neuroprotection. These findings may provide new clues to deepen our understanding of PD pathogenesis.