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Abstract This study was performed on Micropterus salmoides to determine growth-linked gene and single nucleotide polymorphism (SNP) markers under carbohydrate diet and varying temperature through RNA-seq and whole-genome re-sequencing. The results showed that growth-related genes were primarily enriched in the fat digestion and absorption signaling pathway, playing a role in lipid transport and metabolism. Fatty acid binding protein 6, bile salt-activated lipase-like, lysophosphatidylcholine acyltransferase 2, phospholipase A2, minor isoenzyme-like, and phospholipase A2, group IB (pancreas) were identified as the crucial genes. The differentially expressed genes between high and low temperatures were enriched in the pentose phosphate pathway, with carbohydrate transport and metabolism were most affected by temperature. Major facilitator superfamily domain containing 10, phosphogluconate dehydrogenase, fructose-1,6-bisphosphatase 1a, and spinster homolog 3 transcript variant X1(spns3) were the shared genes affected by temperature. From all the common genes, 10 growth-associated SNP markers were identified. The TT genotype at rs7781 was associated with lower body weight, while AA genotype at rs31434173 and CC genotype at rs31435313 showed positive correlation with body weight. Analogously, the GG genotype at rs31436887 and AA genotype at rs31438769 also found to characterize better growth performance. At low temperature, individuals with the AA genotype at rs11506587 and rs31435313 exhibited the slowest growth. For the genotypes labeled with rs11510589, the GG individual grew faster than the AA individual, whereas the opposite phenomenon occurred in these genotypes when labeled with rs11511314. The genotypes at rs32970704 and rs32967921 showed no growth correlation. The AA genotype at rs31435313 in spns3 had the slowest growth under a carbohydrate-rich diet regardless of the temperature. Our study presents candidate genes and SNP markers associated with growth influenced by carbohydrate and temperature, providing basis for the development of M. salmoides strain that better accepts carbohydrate diets at varying temperature.

In order to optimize the parameters for reversing masculinization and establish the techniques for sex induction of pseudo-males and creation of all-female fry in largemouth bass (Micropterus salmodies, LMB), 15-day-old LMB (1.00 ± 0.10 cm in length, 0.10 ± 0.01 g in weight) were fed a diet supplemented with either 17α-methyltestosterone (MT) or letrozole (LE) and their combination. The experimental groups were M20 (20 mg/kg MT), L20 (20 mg/kg LE) and M10L10 (10 mg/kg MT and 10 mg/kg LE). The control group, named C, was not feed MT or LE. After 60 days, exogenous hormone in the diets was stopped and the effects of MT and LE on growth, male ratio, and gonadal development in LMB were evaluated. At 12-month-old, blood and gonadal tissue samples were collected to measure sex steroid hormones levels, analyze expression levels of dmrt1 and cyp19a1a genes, as well as examine the gonads morphology. The results showed no significant differences in growth between the experimental groups and the control group after a 60-day feeding period with the formulated diet (p > 0.05). The sex reversal ratio of M20, L20, M10L10 were 95.00%, 80.00%, 76.47%, respectively. The gonadal tissue sections showed that the gonadal structure of masculinized fish morphologic resembled that of control male fish. At 12-month-old, the sex reversal ratio in M20, L20, M10L10 and C groups were 100%, 86.67%, 73.33% and 50.00%, respectively. The testicular of pseudo-male fish in the M20 group exhibited well-developed morphology similarities to that of the control group males. However, the testes of pseudo-male fish in the L20 and M10L10 groups were smaller size Estradiol (E2) levels in the experimental groups was significantly lower than those in the control group females (p < 0.05), while testosterone (T) levels were significantly higher than that of the control group (p < 0.05). Compared to the female fish in the control group, pseudo-male fish from all experimental groups showed significantly upregulated expression of dmrt1 (p < 0.05), and significantly downregulated expression of cyp19a1a (p < 0.05). Pseudo-males selected from group M20 exhibited a significantly higher proportion of female offspring (92.00%) compared to the control group (46.50%). In summary, 20 mg/kg MT was the optimal inducing concentration.

The sex determination system of largemouth bass (Micropterus salmoides, LMB) is XX/XY; however, the underlying molecular mechanisms involved in early sex differentiation, gonadal development, and exogenous hormone-induced sex reversal remain unknown. In this study, LMB at 15 days post-hatching (dph) were fed diets containing 20 mg/kg of 17α-methyltestosterone (17α-MT) or 30 mg/kg of 17β-estradiol (17β-E2) for 60 days, respectively. Serum steroid levels, histological observations of the gonads, and identification of sex-specific markers were employed to screen the gonads of 60-day-old normal female fish (XX-F), normal male fish (XY-M), 17β-E2 induced pseudo-female fish (XY-F), and 17α-MT-induced pseudo-male fish (XX-M) for transcriptome sequencing in order to uncover genes and pathway involved in the process of sexual reversal. The results from histology and serum sex steroid hormone analysis showed that both 17α-MT and 17β-E2 were capable of inducing sex reversal of LMB at 15 dph. Transcriptome results revealed a total of 2,753 genes exhibiting differential expression, and the expression pattern of these genes in the gonads of XX-M or XY-F resembled that of normal females or males. The male sex-biased genes that are upregulated in XX-M and downregulated in XY-F are referred to as key genes for male reversal, while the female sex-biased genes that are upregulated in XY-F and downregulated in XX-M are referred to as key genes for female reversal. Finally, 12 differentially expressed genes (DEGs) related to male sex reversal were screened, including star2, cyp17a, cyp11b1, dmrt1, amh, sox9a, katnal1, spata4, spata6l, spata7, spata18 and foxl3. 2 DEGs (foxl2a and cyp19a1b) were found to be associated with female sex reversal. The changes in these genes collectively influence the direction of sex differentiation of LMB. Among them, star2, dmrt1 and cyp19a1b with significantly altered expression levels may play potentially crucial role in the process of gender reversal. The expression patterns of 21 randomly selected genes were verified using qRT-PCR which confirmed the reliability and accuracy of the RNA-seq results. These findings not only enhance our understanding of the molecular basis underlying sex reversal but also provide crucial data support for future breeding research on unisexual LMB.

Heat stress has become a significant issue in Largemouth bass (Micropterus salmoides, LMB). Identifying populations with superior heat tolerance abilities contribute to the breeding of new varieties with stress resistance. In this study, three populations of Northern LMB, including “YouLu No.3″ LMB (YL3), wild Northern LMB (NLMB) and Taiwan LMB (TW), as well as one Florida LMB population (M. floridanus, FLMB) were subjected to chronic heat stress. After being exposed to a temperature of 34 ℃ for 60 days, the FLMB group showed the highest final mean body weight (FBW), survival rate (SR), specific growth rate (SGR), and the lowest feed coefficient ratio (FCR) compared to the three Northern LMB groups. The lowest SR was observed in the TW group, while the lowest FBW and SGR, as well as the highest FCR were observed in the NLMB group. The FLMB group showed the lowest damage to the liver, with small focal infiltrations of inflammatory cells. However, the degree of liver damage was gradually worsened in the NLMB, YL3, and TW groups. The NLMB group had a small number of inflammatory cells, while the TW group had more lipid vacuoles and inflammatory cells. The FLMB group exhibited the highest activities of pepsin and lipase, whereas the NLMB group showed the lowest activity of amylase. Compared to the three Northern LMB groups, the FLMB group exhibited higher expressions of HSP60/70 and HSP90aa1/b1. Additionally, the YL3 group exhibited higher expressions of HSP60 and HSP90aa1/b1 compared to the NLMB and TW groups. In conclusion, our results indicated that the FLMB population had better chronic heat tolerance than the Northern LMB populations. Additionally, the YL3 population exhibited superior heat tolerance compared to the TW and NLMB populations. Our study provides valuable information for the future selective breeding of LMB varieties.

Abstract Intramedullary tumors are a class of central nervous system tumors with an incidence of 2 to 4%. As they are located very deep and frequently cause postoperative neurological complications, surgical resection is difficult. In recent years, many surgeons have performed electrophysiological monitoring to effectively reduce the occurrence of postoperative neurological complications. Modern electrophysiological monitoring technology has advanced considerably, leading to the development of many monitoring methods, such as SSEPs, MEPs, DCM, and EMG, to monitor intramedullary tumors. However, electrophysiological monitoring in tumor resection is still being studied. In this article, we discussed the different monitoring methods and their role in monitoring intramedullary tumors by reviewing previous studies. Intratumorally tumors need to be monitored for a summary of the condition of the patient. Only by using various monitoring methods flexibly and through clear communication between surgeons and neurophysiological experts can good decisions be made during surgery and positive surgical results be achieved.

Abstract Acceptance of artificial pelleted diets contributes to increasing the cultured areas and output of carnivorous fish. However, the mechanism of acceptance of artificial pelleted diets remains largely unknown. In this study, the easy acceptance of artificial pelleted diets (EAD) group and the not easy acceptance of artificial pelleted diets (NAD) group of Largemouth bass (Micropterus salmoides) were divided based on the ratios of stomach weight/body weight (SB) after 0.5 h feeding, which was bigger than 18% in the EAD group and ranged from 8 to 12% in the NAD group. Through transcriptome and proteome sequencing, a total of 2463 differentially expressed genes (DEGs) and 230 differentially expressed proteins (DEPs) were identified, respectively. Integrated analyses of transcriptome and proteome data revealed that 152 DEPs were matched with the corresponding DEGs (named co-DEGs-DEPs), and 54 co-DEGs-DEPs were enriched in 16 KEGG pathways, including the metabolic pathways, steroid biosynthesis, fatty acid biosynthesis, etc. Furthermore, 3 terpenoid backbone biosynthesis-related genes (Hmgcr, Hmgcs, and Fdps) in metabolic pathways, 10 steroid biosynthesis-related genes (Fdft1, Sqle, Lss, Cyp51a1, Tm7sf2, Nsdhl, Hsd17b7, Dhcr24, Sc5d, and Dhcr7), and 3 fatty acid biosynthesis-related genes (Acaca, Fasn, and Ascl) were all up-regulated in the EAD group, suggesting that the lipid metabolism pathway and steroid biosynthesis pathway play important roles in early food habit domestication in Largemouth bass. In addition, the detection results of randomly selected 15 DEGs and 15 DEPs indicated that both transcriptome and proteome results in the study were reliable. Our study provides useful information for further research on the mechanisms of food habit domestication in fish.

Abstract Background Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. Methods This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. Results A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. Conclusion The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.

Abstract Background Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. Case presentation We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. Conclusions Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.

To investigate the effects of replacing fish meal with fermented Antarctic krill meal on growth performance, body color, and serum biochemical indexes of koi carp, 450 koi carp with an average body weight of (4.92±0.22) g were randomly divided into five groups with three replicates per group and 30 fish per replicate. In the control group, we added unfermented defatted Antarctic krill meal, and in the experimental groups, we added defatted Antarctic krill meal fermented by Enterococcus faecalis, Lactobacillus plantarum, Clostridium butyricum, and compound bacteria (1:1:1), which were termed as ES (control group), EF, LP, CB, and MIX, respectively. The addition amount of Antarctic krill meal in each group was 200 g/kg, and the experiment lasted for 70 days. The results showed the following: Compared with those in the control group, the replacement of fish meal with fermented Antarctic krill meal significantly improved final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) (P0.05). Based on the above results, using complex bacteria to ferment krill meal in the koi carp feed is recommended with a 20% addition level of defatted krill meal, which can effectively improve the absorption and conversion utilization rate of krill meal.

The use of fertilizers is mainly adopted in arid regions to improve the soil carbon (C) pool and crop productivity. However, the mechanisms underlying improvements in dryland wheat field soils related to microbial metabolic activity and community structure remain poorly understood. Therefore, a field experiment with four fertilization treatments and no fertilizer as the control (CK) was conducted for 10 years in a semi-arid region of China. The results revealed that the combined application of chemical and organic fertilizers (fermented chicken manure) clearly increased the levels of soil organic carbon (SOC), dissolved organic carbon (DOC), and light-fraction organic carbon (LFOC) by 13.54–16.72%, 6.96–9.01%, and 11.00–13.51%, respectively, compared to the sole use of chemical fertilizers (FP treatment). Moreover, the combined treatment not only enhanced the metabolic activity of microorganisms concerning carbon source utilization but also increased the diversity of the bacterial community. This caused noticeable changes in the composition of the bacterial community. A Mantel test analysis revealed that Bacteroidetes and Mortierellomycota significantly enhanced the metabolic activity associated with carbohydrate, amino acid, and carboxylic acid C sources. Actinobacteria, Bacteroidetes, and Mortierellomycota facilitated the accumulation of active C and particulate organic carbon (POC), whereas Mortierellomycota specifically promoted the accumulation of heavy-fraction organic carbon (HFOC), thereby collectively influencing the SOC content. The combined application of chemical and organic fertilizers increased the abundance of Bacteroidetes and Mortierellomycota. This enhancement improved the metabolic utilization of carbohydrates, amino acids, and carboxylic acids, resulting in alterations in the types and quantities of soil metabolites. Consequently, these alterations ultimately affect the composition and quantity of the SOC pool in arid agroecosystems. In conclusion, the combined application of balanced NPK fertilizers and organic fertilizers has a strong positive effect in improving soil microbial activity and the soil C pool.

Abstract Background Cytomegalovirus (CMV) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, it is not clear whether the anti-CMV treatment has an impact on the prognosis of SLE patients with CMV infection. We aimed to analyze the clinical characteristics and prognosis of CMV infection in pediatric SLE (pSLE) and to evaluate the effect of anti-CMV treatment on pSLE outcome. Methods A retrospective study including 146 pSLE from 2012 to 2021 was conducted. CMV-positive and CMV-negative groups were compared by univariate analysis and stepwise logistic multiple regression to analyze the clinical characteristics of CMV infection in pSLE. Generalized estimating equations (GEE) were used to model the longitudinal dynamics of pSLE disease activity with or without CMV infection and anti-CMV treatment. Results The CMV infection rate was 74.7% (109/146) in this pSLE cohort. CMV-positive pSLE patients were more likely to present positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement (P < 0.05). Survival analysis showed that CMV-positive pSLE patients were more prone to disease flare and poorer outcomes. GEE modeling indicated that CMV phosphoprotein 65 (pp65) titers were positively correlated with SLEDAI-2K, and anti-CMV treatment could better reduce pSLE activity than non-treatment (P < 0.05). Conclusions CMV infection is highly prevalent among pSLE patients. Positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement were significant clinical clues indicating CMV infections in pSLE. CMV infection is correlated with higher disease activity and poorer outcome. Anti-CMV treatment can reduce disease activity and flares.

As a representative genetic and economic trait, pigmentation has a strong impact on speciation and adaptation. However, information and reports on microRNAs (miRNAs) associated with pigmentation remain limited. The Midas cichlid fish, with three typical distinct stages of body color pattern, “black-gray-gold”, is an ideal model system for investigating pigmentation traits. In this study, miRNA libraries from scale tissues with the attached epidermis of Midas cichlids at three distinct stages of color transformation, black (B), transition (T), and gold (G), were sequenced using Illumina sequencing technology. In total, 53 (B vs. G), 88 (B vs. T), and 57 (T vs. G) miRNAs were differentially expressed between the respective groups. Target genes of the identified miRNAs were predicted, and the results showed that multiple target genes were related to pigmentation and pigment–cell differentiation. The miRNA–mRNA regulatory network suggests that miR-183-x and miR-133-x were predicted to be involved in regulating morphological color changes in Midas cichlids. The results advance our understanding of potential functions of miRNAs in skin pigment differentiation and early skin color fading of fishes.

Affected by the continuously rising temperature, thermal stress leads to a delinked growth rate and resistance to stress in cultured largemouth bass (Micropterus salmoides, LMB) in China. Identification of LMB with better thermal resistance will benefit the breeding of new varieties. However, there has been limited reporting on the evaluation to identify LMB with better thermal resistance. LMB consists of the northern LMB (Micropterus salmoides salmoides, NLMB) and the Florida LMB (Micropterus salmoides floridanus, FLMB). Due to their different geographical distributions, it has been suggested that FLMB exhibit better thermal resistance compared to NLMB. In this study, NLMB and FLMB were subjected to thermal stress for 3 h (acute) and 60 d (chronic) at 33 °C, respectively. Subsequently, the variations of 12 candidate biomarkers between NLMB and FLMB were analyzed. Exposure to acute thermal stress significantly increased plasma cortisol, blood glucose, and lactate levels; activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glucose kinase (GK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and glucose 6 phosphatase (G6Pase); and the expressions of hsp70 and hsp90 in both NLMB and FLMB (p < 0.05). Compared to NLMB, FLMB exhibited a lower plasma cortisol level and a higher expression of hsp90 under acute thermal stress (p < 0.05). Exposure to chronic thermal stress significantly increased plasma cortisol and blood glucose levels, as well as activities of GK, PK, LDH, and G6Pase, as well as expressions of hsp70 and hsp90 in both NLMB and FLMB (p < 0.05). Additionally, FLMB showed a lower expression of hsp70 compared to NLMB (p < 0.05). In conclusion, our results showed that LMB with lower plasma cortisol level and higher expression of hsp90 under acute thermal stress, as well as lower expression of hsp70 under chronic thermal stress were suggested to have better thermal resistance. Our study provides valuable information for identifying and breeding LMB varieties with better thermal resistance in the future.

Pyrin, a protein encoded by the MEFV gene, plays a vital role in innate immunity by sensing modifications in Rho GTPase and assembling the pyrin inflammasome, which in turn activates downstream immune responses. We identified a novel and de novo MEFV p.E583A dominant variant in 3 patients from the same family; the variant was distinct from the previously reported S242 and E244 sites. These patients exhibited a phenotype that diverged from those resulting from classical MEFV gene mutations, characterized by the absence of recurrent fever but the presence of recurrent chest and abdominal pain. Colchicine effectively controlled the phenotype, and the mutation was found to induce pyrin inflammasome assembly and activation in patients’ peripheral blood mononuclear cells (PBMCs) and cell lines. Mechanistically, truncation experiments revealed that the E583A variant affected the autoinhibitory structure of pyrin. Our study offers insights into the mechanisms underlying pyrin inflammasome activation.

In this study, the complete mitochondrial genome sequence of the New Guinea tiger fish Datnioides campbelli (Whitley 1938) (Lobotiformes: Datnioididae) was sequenced by next-generation sequencing method. The assembled mitochondrial genome consists of 13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes, with a length of 16,416 bp. The total base composition of the mitogenome of D. campbelli was 29.31% for A, 29.02% for C, 15.14% for G and 26.54% for T. A phylogenetic tree based on 13 protein-coding genes (PCGs) provides important molecular data for further phylogeographic and evolutionary analysis of Lobotiformes.

The Loess Plateau in China has long grappled with issues such as chronic soil erosion, poor soil structure, and diminished organic matter. Soil organic carbon plays a crucial role in enhancing soil fertility, and fertilization is a key tool that influences it. In a comprehensive field experiment, we examined five fertilization methods: no fertilization (CK); traditional fertilization used by local farmers (FP); nutrient-balanced fertilization with nitrogen, phosphorus, and potassium (OF); chemical fertilizers used in conjunction with organic fertilizers (OFM); and chemical fertilizers paired with bio-organic fertilizers (OFB). Our findings revealed that the OFM and OFB treatments were the most effective, explaining 84.35% and 81.26% of the variation in soil carbon sequestration, respectively. Further, the OF, OFM, and OFB treatments demonstrated superior effectiveness compared with the FP treatment in enhancing the soil carbon fractions. However, these fertilization patterns did not significantly alter the active-to-inert carbon ratio of the soil. OF, OFM, and OFB treatments enhanced the stability of soil carbon pools more than FP treatment. In structural equation modeling, factors such as microbial biomass nitrogen and phosphorus, soil pH, and β-N-acetyl glucosidase indirectly exhibited a limiting effect on the carbon pool stability index (CPSI), while β-glucosidase displayed an indirect positive correlation with the carbon fractions. In contrast, dissolved organic carbon, low-molecular-weight organic carbon, high-molecular-weight organic carbon, and crop yield demonstrated direct positive correlations with the CPSI. Consequently, both a balanced application of chemical fertilizers and the combination of organic and chemical fertilizers were effective in enhancing and sustaining the soil’s organic carbon content, thereby contributing to soil fertility stability. To this end, this study can inform the efficient selection and use of fertilizers, improving crop yield and soil carbon content.

Abstract Background NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature. Results Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports. Conclusion In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.

Intelligent Financial Advisors (IFAs) in online financial applications (apps) have brought new life to personal investment by providing appropriate and high-quality portfolios for users. In real-world scenarios, identifying potential clients is a crucial issue for IFAs, i.e., identifying users who are willing to purchase the portfolios. Thus, extracting useful information from various characteristics of users and further predicting their purchase inclination are urgent. However, two critical problems encountered in real practice make this prediction task challenging, i.e., sample selection bias and data sparsity. In this study, we formalize a potential conversion relationship, i.e., user → activated user → client and decompose this relationship into three related tasks. Then, we propose a Multitask Feature Extraction Model (MFEM), which can leverage useful information contained in these related tasks and learn them jointly, thereby solving the two problems simultaneously. In addition, we design a two-stage feature selection algorithm to select highly relevant user features efficiently and accurately from an incredibly huge number of user feature fields. Finally, we conduct extensive experiments on a real-world dataset provided by a famous fintech bank. Experimental results clearly demonstrate the effectiveness of MFEM.

PurposeThe aim of this study was to improve the intratumoral accumulation of an antibody–drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study.MethodsThe in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics–pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132.ResultsIn vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264’s exposure in tumor tissue was 4.6-fold higher than that of IMMU-132.ConclusionsCompared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.

In order to improve the glucose utilization capacity of largemouth bass (Micropterus salmoides), responses to glucose overload between two strains (Y: breeding strain; W: wild strain) were compared at 0, 6, 12, and 24 h after glucose injection (1.67 g/kg). The data revealed that plasma glucose in the Y strain (

Summary: Understanding the evolutionary history of the highly diverse ray-finned fishes has been challenging, and the development of more universal primers for phylogenetic analyses may help overcoming these challenges. We developed FishPIE, a nested PCR primer set of 82 phylogenetically informative exon markers, and tested it on 203 species from 31 orders of Actinopterygii. We combined orthologous sequences of the FishPIE markers obtained from published genomes and transcriptomes and constructed the phylogeny of 710 species belonging to 190 families and 60 orders. The resulting phylogenies had topologies comparable to previous phylogenomic studies. We demonstrated that the FishPIE markers could address phylogenetic questions across broad taxonomic levels. By incorporating the newly sequenced taxa, we were able to shed new light on the phylogeny of the highly diverse Cypriniformes. Thus, FishPIE holds great promise for generating genetic data for broad taxonomic groups and accelerating our understanding of the fish tree of life.

Largemouth bass (Micropterus salmoides L.) is generally considered to comprise two subspecies, Florida bass (M. floridanus) and Northern Largemouth bass (M. salmoides), which have biological characteristic differences because of their geographical distribution. In this study, whole-genome re-sequencing was performed among 10 Florida and 10 Northern largemouth bass, respectively. In total, 999,793 SNPs and 227,797 InDels were finally identified, and 507,401 SNPs (50.75%) and 116,213 InDels (51.01%) were successfully mapped to annotated 18,629 genes and 14,060 genes, respectively. KEGG classification indicated that most of these genes were focused on the pathways including signal transduction, transport and catabolism, and endocrine system. Genetic diversity analysis indicated that Florida largemouth bass had higher genetic diversity than Northern largemouth bass, indicating that the germplasm quality of Northern largemouth bass had markedly reduced in China. To examine the accuracies of the identified markers, 23 SNPs and eight InDels (the insertions or deletions of more than 45 bp) were randomly selected and detected among Florida largemouth bass, Northern largemouth bass, and their F1 hybrids. The detection efficiencies of all the markers were higher than 95%; nineteen SNPs and three InDels could accurately distinguish the two subspecies and their F1 hybrids with 100% efficiencies. Moreover, the three InDel markers could clearly distinguish the two subspecies and their F1 hybrids with a PCR-based agarose gel electrophoresis. In conclusion, our study established a simple PCR-based method for the germplasm identification of largemouth bass, which will be useful in the germplasm protection, management, and hybridization breeding of largemouth bass.

Abstract Background Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Few Chinese cases have been reported. We describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and non-Chinese patients. Methods Primary immunodeficiency disease panel or whole-exome sequencing was performed for suspected cases, and assays for adenosine deaminase 2 (ADA2) enzyme activity were also carried out for the patients and their parents. Case reports of Chinese and non-Chinese patients with DADA2 were searched in PubMed and Chinese national databases. Results Seven unrelated children from China with DADA2 were included in our study. Five were identified at Peking Union Medical College Hospital, and two had been reported previously (1 on PubMed and 1 in Chinese literature). Fourteen mutations in ADA2 were identified, 7 of which have not previously been reported in non-Chinese patients. Four children who underwent enzymatic analysis had lower ADA2 activity compared with their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, and neurologic involvement. Treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on phenotype and severity. Conclusion This study includes the largest number of Chinese DADA2 patients to date. We recommend the combination of enzymatic analysis with gene screening to confirm the diagnosis. Different genotypes were observed among Chinese DADA2 patients; most phenotypes were similar to those of non-Chinese DADA2 patients, except for growth retardation. Disease remission might not be achieved with anti-IL-6 therapy.

ObjectiveThis study aimed to assess the efficacy and safety of 2 Janus kinase (JAK) inhibitors (jakinibs) tofacitinib and ruxolitinib in the treatment of type I interferonopathies patients including STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutières syndrome (AGS), and spondyloenchondrodysplasia with immune dysregulation (SPENCD).MethodsA total of 6 patients were considered in this study: 2 patients with SAVI, 1 patient with AGS1, 1 patient with AGS7, and 2 patients with SPENCD. Clinical manifestations, laboratory investigations, radiology examinations, treatment, and outcomes were collected between November 2017 and November 2021 in Peking Union Medical College Hospital. The disease score for patients with SAVI and AGS scale for patients with AGS were documented. The expression of 6 interferon-stimulated genes (ISGs) was assessed by real-time PCR.ResultsThree patients (1 patient with SAVI, 2 patients with AGS) were treated with ruxolitinib and 3 patients (1 patient with SAVI, 2 patients with SPENCD) were treated with tofacitinib. The mean duration of the treatment was 2.5 years (1.25–4 years). Upon treatment, cutaneous lesions and febrile attacks subsided in all affected patients. Two patients discontinued the corticoid treatment. Two patients with SAVI showed an improvement in the disease scores (p

Abstract Background Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients’ severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients. Methods The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse. Results The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01–16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models. Conclusions The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.

Selective immunoglobulin A deficiency (SIgAD) is considered to be the most common human primary immune-deficiency disease in the world. However, the incidence in China is obviously lower than Caucasian races. The definition of SIgAD has changed over time with the progress of people's understanding. The scientific community did not reach a consensus on the definition until 1999. As a result, many previously reported cases need to be excluded under the current definition. SIgAD can lead to several spectra of diseases including infections and autoimmune diseases. We retrospectively summarized the SIgAD patients in Peking Union Medical College Hospital (PUMCH), and summarized the Chinese SIgAD reported in China and abroad in past 40 years. Fourty three SIgAD patients were confirmed in the study, in which 9 were healthy without clinical symptoms. Of the 34 patients with clinical symptoms, recurrent infections were found in 29 (85.3%) patients; 13 (38.2%) patients were with autoimmune diseases; 6 (17.6%)cases had allergic symptoms; 3 patients (8.8%) were with tumors, only one case (2.9%) had a family history. Compared with other countries, sIgAD patients in China showed similar symptoms, but the rate of recurrent infections and autoimmune diseases were higher than some other countries; most of the allergic symptoms are drug allergy, different with the allergic sequelae reported in other countries, such as asthma, rhinitis, food allergy and atopic dermatitis; and it is rare to have family history in Chinese patients. We also figured out that more female SIgAD patients tend to have more autoimmune diseases than men (P = 0.039). Keywords: Autoimmune diseases, Chinese, Clinical manifestations, Recurrent infections, Selective Immunoglobulin A Deficiency (SigAD)

Abstract Background Primary immunodeficiency diseases (PIDs) patients may show systemic lupus erythematosus (SLE)-like autoimmunity disorders, such as cytopenias, as well as polyarthritis, which leads to concerns of misdiagnosis. We diagnosed three RALD cases between 2015 and 2018, who were suspected as SLE and summarized clinical characteristics. Methods We collected and analyzed the clinical data of the 3 cases. DNA was extracted from the patients’ and their parents’ peripheral blood as well as oral mucosa cells, hair follicles, and nails. Genes were detected with the application of gene trapping high-throughput sequencing using PIDs panel and suspicious gene or mutation was further verified by Sanger sequencing. Results 1. Clinical features: On the one hand, the patients presented with severe thrombocytopenia, facial erythema, arthritis, positive autoantibodies and other manifestations, supporting the diagnosis of SLE. On the other hand, symptoms including early onset ages, recurrent infections, lymphadenopathy, hepatosplenomegaly, monocytosis and hypergammaglobulinemia, were common observed in PIDs. 2. Gene analysis: NRAS mutations (c.38G > A, p.G13D or c.37G > T, p.G13C) were found in the blood of the patients. Besides, the same set of mutations was detected in buccal mucosa of patient 1 and nails of patient 3 while the frequency was much lower. However, no mutation was found in other tissues or in their parents’ blood. Consequently, they were NRAS somatic mutated RALD. Conclusions For those early-onset SLE-like patients with predominant hematologic disorders, monocytosis, recurrent infectious history, accompanied with hepatosplenomegaly and lymphadenopathy, a genetic screening of PIDs might be required.

Background: Targeted urinalysis has been suggested to improve screening efficiency in adults. However, there is no well-defined target population in children yet, with limited information on the risk factors for urinalysis abnormalities.Methods: Children from infants to 17 years old were randomly selected. Dipstick urinalysis was initially performed. Among those who were abnormal, a repeat dipstick or dipstick with microscopic urinalysis was performed for confirmation.Results: In total, 70,822 children were included, with 37,866 boys and 32,956 girls. Prevalence of abnormal urinalysis was 4.3%. Age was significantly associated with abnormal urinalysis, with the highest prevalence among 12–14-year-olds. Girls were 2.0 times more likely to exhibit abnormalities. Compared with children whose guardians had a college degree or higher, those whose guardians had a high school degree or lower had a higher likelihood of abnormalities. Geographic location was also associated with abnormal results.Conclusion: Girls, children aged 12–14 years old, and children whose guardians had a low educational level and children in certain geographic locations were significantly associated with abnormal urinalysis. Identification of children at high risk would contribute to targeted urinalysis screening.

The present study was undertaken to decipher the role of HOXC10 gene in regulating the growth and metastasis of prostate cancer. The results revealed significant (p

Objective: Monogenic autoinflammatory diseases (AIDs) are inborn disorders caused by innate immunity dysregulation and characterized by robust autoinflammation. We aimed to present the phenotypes and genotypes of Chinese pediatric monogenic AID patients.Methods: A total of 288 pediatric patients clinically suspected to have monogenic AIDs at the Department of Pediatrics of Peking Union Medical College Hospital between November 2008 and May 2019 were genotyped by Sanger sequencing, and/or gene panel sequencing and/or whole exome sequencing. Final definite diagnoses were made when the phenotypes and genotypes were mutually verified.Results: Of the 288 patients, 79 (27.4%) were diagnosed with 18 kinds of monogenic AIDs, including 33 patients with inflammasomopathies, 38 patients with non-inflammasome related conditions, and eight patients with type 1 interferonopathies. Main clinical features were skin disorders (76%), musculoskeletal problems (66%), fever (62%), growth retardation (33%), gastrointestinal tract abnormalities (25%), central nervous system abnormalities (15%), eye disorders (16%), ear problems (9%), and cardiopulmonary disorders (8%). The causative genes were ACP5, ADA2, ADAR1, IFIH1, LPIN2, MEFV, MVK, NLRC4, NLRP3, NLRP12, NOD2, PLCG2, PSMB8, PSTPIP1, TMEM173, TNFAIP3, TNFRSF1A, and TREX1.Conclusions: The present study summarized both clinical and genetic characteristics of 18 kinds of monogenic AIDs found in the largest pediatric AID center over the past decade, with fever, skin problems, and musculoskeletal system disorders being the most prevalent clinical features. Many of the mutations were newly discovered. This is by far the first and largest monogenic AID report in Chinese pediatric population and also a catalog of the phenotypic and genotypic features among these patients.

Objective This study aimed to investigate the prognostic value of the lateral spread response (LSR) for predicting surgical outcomes following microvascular decompression (MVD) in patients with hemifacial spasm. Methods Seventy-three patients with hemifacial spasm underwent MVD with intraoperative LSR monitoring. Surgical outcomes were evaluated 1 week and 1 year after MVD and correlations between LSR characteristics and surgical outcomes were analyzed. Results The LSR disappeared completely in 61 patients during surgery (Group A; prior to insertion of Teflon felt pledgets in 11, after insertion of pledgets in 50), disappeared partially in nine patients (Group B), and remained unchanged in three patients (Group C). Fifty-five patients showed short-term and 61 patients showed long-term clinical cures during the follow-up period. The short-term and long-term cure rates were significantly higher in Group A than in Group C. There was no correlation between the time of complete LSR disappearance and surgical outcomes. Conclusions Disappearance of the LSR during MVD is correlated with the surgical outcomes. Intraoperative LSR monitoring is a reliable approach for predicting the prognosis of hemifacial spasm following MVD, but the time at which LSR disappears is not a prognostic indicator.

We determined the complete mitochondrial genome of Moolgarda perusii, which is 16,781 bp in length, and contains 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and a complete control region. The total base composition of the mitogenome is 28.7% T, 27.0% C, 28.5% A, and 15.9% G. Of the 13 PCGs, 11 PCGs start with an ATG codon. Eight PCGs use TAA/TAG/AGA as the termination codon, whereas five PCGs have incomplete stop codon TA/T. This study would be useful for further studying population genetics and understanding the phylogenetic relationship of the family Mugilidae.

We determined the complete mitochondrial genome of Lactoria cornuta, which is 16,495 bp in length with an A + T content of 57.37%, and contains 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a complete control region. The total base composition of the mitogenome is 28.2% T, 26.7% C, 29.2% A and 15.9% G. Of the 13 protein-coding genes, 12 genes start with an ATG codon, except for COX1 with GTG. Ten genes use TAA or AGA as the termination codon, whereas three (COX2, ND4, and Cyt b) have incomplete stop codon T. This study would provide useful genetic information for phylogenetic and species idenfication of the family Ostraciidae.

Background: Familial Mediterranean fever (FMF) is an inherited auto-inflammatory disorder and is extremely rare in Chinese. This study aimed to investigate the demographic, clinical, and genetic features of FMF in a series of Chinese pediatric patients.Methods: This was a retrospective case series of children with recurrent febrile or inflammatory episodes and referred to the Peking Union Medical College Hospital between 06/2013 and 06/2018. All suspected patients were genetically diagnosed and met the Tel-Hashomer criteria for FMF. Demographic, clinical, genetic, and treatment characteristics were collected. Descriptive statistics were used.Results: Eleven patients were included (seven boys and four girls). The median age at the time of disease onset was 7.1 (range, 3–12) years, while the median age at diagnosis was 10.9 (range, 6–15) years. The median delay in diagnosis was 2.1 years (range, 6 months to 6.7 years). Fever (100%, 11/11) was the most common symptom, followed by joint pain (63.6%, 7/11), rash (54.5%, 6/11), abdominal pain (36.4%, 4/11), and oral ulcers (18.2%, 2/11), without evidence of amyloidosis. C-reactive protein (81.8%, 9/11) and erythrocyte sedimentation (90.9%, 10/11) were increased during attacks. All patients harbored one to five different MEFV mutations, with E148Q and L110P being the most frequent. A novel non-synonymous mutation F636Y in exon 10 was discovered. Favorable responses to colchicine was observed in all six treated patients.Conclusion: The most common variants in our study were E148Q and L110P. F636Y may found for the first time. Colchicine led to favorable responses in all treated patients.

Temporal lobe epilepsy is the most common and often drug-resistant type of epilepsy in the adult and aging populations and has great diversity in etiology, electro-clinical manifestations, and comorbidities. Kindling through repeated brief stimulation of limbic structures is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling can induce spontaneous recurrent seizures in several animal species. However, kindling studies in middle-aged, aging, or aged animals remain scarce, and currently, little is known about kindling-induced behavioral changes in middle-aged/aging animals. We therefore attempted to provide more information in this area using a mouse model of extended hippocampal kindling. We conducted experiments in middle-aged mice (C57BL/6, male, 12–14 months of age) to model new-onset epilepsy in adult/aging populations. Mice experienced twice daily hippocampal stimulations or handling manipulations for 60–70 days and then underwent continuous electroencephalogram (EEG)-video monitoring to detect spontaneous recurrent seizures. Extended kindled mice consistently exhibited spontaneous recurrent seizures with mean incidences of 6–7 events per day, and these seizures featured EEG discharges and corresponding convulsions. The handling control mice showed neither seizure nor aberrant EEG activity. The two groups of mice underwent the Morris water maze test of spatial learning and memory 1–2 weeks after termination of the kindling stimulation or handling manipulation. During visible platform trials, the kindled mice took a longer distance and required more time than the control mice to find the platform. During hidden platform trials, the kindled mice showed no improvement over 5-day trials in finding the platform whereas the control mice improved significantly. During probe tests in which the hidden platform was removed, the kindled mice spent less time than the controls searching in the correct platform location. There were no significant differences between the kindled and control mice with respect to swim speed or total locomotor activity in an open-field test. Together, these observations indicate that the extended kindled mice with spontaneous recurrent seizures are impaired in spatial learning and memory as assessed by the Morris water maze test. We postulate that the extended hippocampal kindling in middle-aged mice may help explore epileptogenic mechanisms and comorbidities potentially relevant to new-onset temporal lobe epilepsy in adult and aging patients. Limitations and confounds of our present experiments are discussed to improve future examinations of epileptic comorbidities in extended kindled mice.

Objective: It has been established that reduced vitamin B12 serum levels are associated with cognitive decline and mental illness. The chronic use of methamphetamine (MA), which is a highly addictive drug, can induce cognitive impairment and psychopathological symptoms. There are few studies addressing the association of MA with vitamin B12 serum levels. This study examined whether the serum levels of B12 are associated with MA addiction.Methods: Serum vitamin B12, homocysteine (Hcy), glucose and triglyceride concentrations were measured in 123 MA addicts and 108 controls. In addition, data were collected on their age, marital status, level of education and Body Mass Index (BMI) for all participants. In the patient group, the data for each subject were collected using the Fagerstrom Test for Nicotine Dependence (FTND), the Alcohol Use Disorders Identification Test (AUDIT), and a drug use history, which included the age of onset, total duration of MA use, the number of relapses and addiction severity.Results: Our results showed that MA addicts had lower vitamin B12 levels (p < 0.05) than those of healthy controls, but Hcy levels were not significantly different between the two groups (p > 0.05). Serum B12 levels were negatively correlated with the number of relapses in the MA group. Furthermore, binary logistics regression analysis indicated that the B12 was an influencing factor contributing to addiction severity.Conclusion: The findings of this study suggest that some MA addicts might have vitamin B12 deficiency, and serum B12 levels may be involved in the prognosis of MA addiction.

The hippocampal circuitry is widely recognized as susceptible to ischemic injury and seizure generation. However, hippocampal contribution to acute non-convulsive seizures (NCS) in models involving middle cerebral artery occlusion (MCAO) remains to be determined. To address this, we occluded the middle cerebral artery in adult C57 black mice and monitored electroencephalographic (EEG) discharges from hippocampal and neocortical areas. Electrographic discharges in the absence of convulsive motor behaviors were observed within 90 min following occlusion of the middle cerebral artery. Hippocampal discharges were more robust than corresponding cortical discharges in all seizure events examined, and hippocampal discharges alone or with minimal cortical involvement were also observed in some seizure events. Seizure development was associated with ipsilateral hippocampal injuries as determined by subsequent histological examinations. We also introduced hypoxia-hypoglycemia episodes in mouse brain slices and examined regional hyperexcitable responses ex vivo. Extracellular recordings showed that the hippocampal CA3 region had a greater propensity for exhibiting single/multiunit activities or epileptiform field potentials following hypoxic-hypoglycemic (HH) episodes compared to the CA1, dentate gyrus, entorhinal cortical (EC) or neocortical regions. Whole-cell recordings revealed that CA3 pyramidal neurons exhibited excessive excitatory postsynaptic currents, attenuated inhibitory postsynaptic currents and intermittent or repetitive spikes in response to HH challenge. Together, these observations suggest that hippocampal discharges, possibly as a result of CA3 circuitry hyperexcitability, are a major component of acute NCS in a mouse model of MCAO.

Background: The aim of this study was to evaluate the clinical performance of VersaTrek 528 compared to BACTEC FX 400 blood culture (BC) systems.Materials and Methods: Simulated and clinically obtained BCs were used in the study. Confirmed bacterial species (n = 78), including 43 Gram-positives, 30 Gram-negatives, and 5 Candida albicans strains, were each inoculated into BC bottles. Clinically obtained BCs were subdivided into two groups, A and B. In group A were 72 BC sets (pair: aerobic and anaerobic) in which a set inoculated with 5 ml blood was processed in the VersaTrek BC system, whilst the one inoculated with 10 ml blood was processed in the FX BC system. In group B, 76 BC sets (pairs) corresponding to 152 VersaTrek bottles and 152 FX bottles were inoculated with the same volume (10 ml) of blood, and processed in each system.Results: In the simulated BC study, 90% (63/70) of the VersaTrek aerobic bottles were positive, which was higher than that of FX 400 (59/70, 84%), but was not statistically significant (P = 0.423). In contrast, FX 400 anaerobic bottles had a higher positive rate than the other BC system (84 vs. 77%), although it was statistically insignificant (P = 0.267). Time to detection of organisms in the two BCs was comparable for both aerobic (P = 0.131) and anaerobic bottles (P = 0.104). In clinical BCs of group A, FX BC system had slightly higher positive rates for both aerobic (11.1 vs. 9.7%, P = 0.312) and anaerobic (8.3 vs. 6.9%, P = 0.375) bottles. However, the difference was not statistically significant. In group B, VersaTrek aerobic bottles had a higher positive rate compared to the other BC system (10.5 vs. 5.2%, P = 0.063). In terms of positive rates of sub-studies A and B, VersaTrek and FX BC systems were comparable.Conclusion: There was no significant difference between the two BC systems in the detection of bacteria and fungi in simulated BCs. In clinical BCs, the performance of the VersaTrek BC system, with inoculation of 5 or 10 ml patient’s blood, was comparable to the FX system with inoculation of 10 ml patient’s blood.

Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10–12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on seizure spread. No gross brain lesions were observed in a set of extended hippocampal kindled mice submitted to histological evaluation. All these data suggests that our model could be considered as a novel mouse model of extended hippocampal kindling. Some limitations remain to be considered.

We describe here a simple, cost-effective apparatus for continuous tethered electroencephalographic (EEG) monitoring of spontaneous recurrent seizures in mice. We used a small, low torque slip ring as an EEG commutator, mounted the slip ring onto a standard mouse cage and connected rotary wires of the slip ring directly to animal's implanted headset. Modifications were made in the cage to allow for a convenient installation of the slip ring and accommodation of animal ambient activity. We tested the apparatus for hippocampal EEG recordings in adult C57 black mice. Spontaneous recurrent seizures were induced using extended hippocampal kindling (≥95 daily stimulation). Control animals underwent similar hippocampal electrode implantations but no stimulations were given. Combined EEG and webcam monitoring were performed for 24 h daily for 5–9 consecutive days. During the monitoring periods, the animals moved and accessed water and food freely and showed no apparent restriction in ambient cage activities. Ictal-like hippocampal EEG discharges and concurrent convulsive behaviors that are characteristics of spontaneous recurrent seizures were reliably recorded in a majority of the monitoring experiments in extendedly kindled but not in control animals. However, 1–2 rotary wires were disconnected from the implanted headset in some animals after continuous recordings for ≥5 days. The key features and main limitations of our recording apparatus are discussed.

Glomerular filtration rate (GFR) is essential for renal function evaluation and classification of chronic kidney disease (CKD), while the reference method in children are cumbersome. In the Chinese children, there was no data about GFR measured through plasma or renal clearance of the exogenous markers, and therefore no validated GFR-estimating tools in this population.We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 87 hospitalized children with renal injury. Using mGFR as the golden standard, we evaluate the efficiency of four different GFR estimation equations (the original and update Schwartz equation, the Filler equation, the CKiD equation) by statistical parameters of correlation, precision and accuracy.In our population, mGFR was 97.0± 31.9 mL/min/1.73m2. The updated Schwartz equation, the Filler equation and the CKiD equation, produced eGFR with strong correlation with mGFR, strong explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis, high intra-class correlation coefficients, high ratio of eGFR within mGFR±10% and eGFR within mGFR±30%, good agreement in CKD staging between eGFR and mGFR. The original Schwartz equation produced eGFR with large bias, poor precision and accuracy.The validated equations to estimate GFR in our patients are the updated Schwartz equation, which is simple for bedside use, the Filler equation and the CKiD equation, which provide more accurate eGFR. The original Schwartz equation should not be applied to estimate GFR in Chinese children with kidney injuries.

OBJECTIVE:The aim of the current study was to determine the contributions of several common mutations in the Mediterranean fever (MEFV) gene, namely, E148Q, M680I, M694V and V726A, to ankylosing spondylitis (AS) susceptibility. METHODS:Two investigators independently searched the literature regarding the association of MEFV with AS in the PubMed, EMBASE, Web of Science, and Scopus databases. They independently selected eligible articles and then extracted data from the included studies. The associations between MEFV mutations and AS risk were assessed with odds ratios (ORs) and 95% confidence intervals (95% CI). Further analyses were conducted with STATA 12.0 software (Stata Corp.; College Station, Texas, USA). RESULTS:Four mutations (E148Q, M680I, M694V and V726A) were genotyped in 869 AS cases and 879 controls from the 8 eligible studies. Of the four mutations, M694V (pooled OR: 3.330, 95% CI: 2.129-5.208) was found to be associated with AS through overall analysis. However, the other mutations demonstrated no relation with AS (pooled ORs: 1.295, 1.258, 1.778; 95% CI: 0.886-1.891, 0.688-2.298 and 0.938-3.371). No significant publication bias was discovered in the meta-analysis. CONCLUSIONS:The present study indicates that the MEFV M694V mutation may contribute to the pathogenesis of AS. The associations between the other mutations and AS need to be validated with more relevant and well-designed studies.