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Clonidine (CLO) preferentially stimulates central α-2-adrenoceptors and causes both desirable and undesirable effects. Undesirable effects include sedation and withdrawal reactions, which occur as a sudden rise in arterial pressure, nervousness, agitation, and increased heart rate. An immunochromatographic test strip was developed for the rapid simultaneous detection of CLO and its cross-reactivity with apraclonidine (ACLO) in pig urine. The antigen CLO-OVA and goat anti-mouse IgG were attached to a nitrocellulose membrane as control line and test line. The cut-off limits of the test strips for CLO and ACLO were found to be 2.5 ng/mL in both 0.01 M PBS (pH 7.4) and pig urine. All the results were obtained within 5 min. The results revealed that the developed method is a sensitive, rapid, and simple tool for the detection of CLO and ACLO.

Abstract Background Human endogenous retroviruses (HERVs) belong to the LTR-retrotransposon family, where the complete HERV sequence contains two long terminal repeats (LTRs) located at each end. Intact LTRs possess highly conserved transcriptional promoter and enhancer sequences, so analyses of HERV insertional polymorphisms are expected to provide greater insights into human genomic variation compared with the conventional analysis of single nucleotide variations. High-throughput sequencing technology is developing but genome-wide investigations of HERVs are methodically challenging, and thus a comprehensive understanding of HERV insertional polymorphisms and target site duplications (TSDs) remains elusive. Results We identified five human-specific insertionally polymorphic sites in HERVK (HML-2), one of the HERV subgroups, by extracting HML-2-deleted sequences from the genomic structural variation database, which we successfully characterized and then updated the existing catalogue of HML-2 insertional polymorphisms. The insertionally polymorphic states were confirmed in a small Japanese population by genomic PCR analysis for four of the five sites identified. Sequencing of the preintegration sites clearly showed that the HML-2 site located at 7p21.2 had 250-base pair (bp) TSDs, which is one of the longest TSDs in HML-2. In addition to these five sites, another insertionally polymorphic site for a non-human-specific HML-2 site was also identified at 6p25.2, which was flanked by 111-bp TSDs and the corresponding ERV locus was also annotated in the genome of non-human primates. Conclusions Our analysis demonstrated the existence of HERV insertions flanked by unconventionally long TSDs, including those with lengths as high as 250 bp. This suggests that the length range of retroviral TSDs is larger than considered previously, which might help to understand how retroviral integration occurs in the host genome.

Background: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroup A and C–tetanus toxoid conjugate vaccine (Hib-MenAC). Methods: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3–5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint. Results: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination. Conclusions: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months.

Controlling the large deformation caused by bed separation failure of thick and soft surrounding rock in gob-side entry retaining is difficult. The deformation and failure modes of thick and soft surrounding rock are summarized and classified based on field research, theoretical analysis, laboratory tests, and actual measurements. Systematic research is conducted on the lithologic characteristics, failure characteristics, and control methods of the surrounding rock. The research findings are as follows: (1) The low strength, softening, and water swelling of thick mudstone, as well as its cataclasis, dilatancy, and long-term creep under strong mining and high stress are the objective reasons for large deformation of the surrounding rock. (2) Due to the weak stability of the surrounding rock-support structure and low collaborative roof side bearing capacity, no complete supporting structure is formed with the supporting system, causing the support body in each area to be crushed one by one, which is the subjective reason for the deformation and failure of the surrounding rock. (3) The deformation and failure characteristics of thick and soft surrounding rock in gob-side entry retaining are primarily divided into eight types: roof bending and sinking type, roof cutting along filling body, rib spalling type, roof fall type, filling body rotation type, filling body crushing type, roof step type, and roof cutting along the coal side. The initial points and key points for a chain reaction of each failure type are determined. (4) The surrounding rock is divided into 10 support zones at four levels, and control technology for “zonal support and overall reinforcement” is put forward. The mechanical effect of the support body in each zone and its role in maintaining the stability of surrounding rock are analyzed. This technology can ensure the integrity of the surrounding rock structure and improve the roof side collaborative bearing capacity.

Objective: Pierson syndrome (OMIM 609049) is a rare autosomal recessive disorder characterized by congenital nephrotic syndrome and complex ocular abnormalities. Severe renal symptoms had be associated with truncating mutations. Few Chinese patients from diverse ethnic background had been evaluated and reported with this syndrome. Here we report the first Uyghur patient with typical Pierson syndrome phenotypes and a novel pathogenic homozygous variant in LAMB2 gene.Method: A thirty-nine-day old Uyghur girl was born to consanguineous parents, the girl presented with general edema, severe hypotonia and bilateral microcoria. Laboratory tests revealed severe proteinuria, microscopic haematuria, hypoalbuminaemia. By the age of 74 days, she died of renal failure and respiratory infection. We detected on mutations of LAMB2 gene by the sanger sequencing.Result:Sanger sequencing detected a homozygous 2-bp deletion (c.2044_2045insTT/p.Cys682Phefs*13) in the exon 16 of LAMB2 gene. Both parents are heterozygous carriers.Conclusion: We reported the first Uyghur case of LAMB2 gene homozygous mutation leading to severe phenotype Pierson syndrome. The clinical presentation of the patient and the novel pathogenic variant detected in this patient added to the overall knowledge of this rare condition.

A new type insulated gate bipolar transistor (IGBT) with electron injection (EI-IGBT) is proposed in which an N+-buried layer is implemented in P-base region. The mechanism of the EI-IGBT is that electrons are injected in both OFF- and ON-state, thus accelerated electron-hole recombination is achieved, resulting in a fast turn-off process. Meanwhile, a low forward voltage drop is obtained due to an enhanced conductivity modulation. The simulation results show that, compared with the conventional IGBT, the proposed EI-IGBT delivers a comparable breakdown voltage while featuring an 80% shorter turn-off time (or a 72% lower turn-off loss) or a 23% lower forward voltage drop, resulting in a reduction of total energy loss.

Objectives: Previous studies in mainland China found ICU nurses to be less satisfied with their jobs and more inclined to leave them than are nurses in other hospital units. We aimed to determine ICU nurses' perspectives on the factors that influence job satisfaction and whether or not to continue working in the ICU. Methods: Nine ICU nurses were asked five open-ended questions to elicit the nurses' perspectives on job satisfaction and intentions to leave. Data were analyzed according to the process described by Knafl and Webster (1988). Core concepts were identified using the constant comparative method. Results: Two themes emerged as major influences on job dissatisfaction: 1) stress experienced from excessive workload demands and the ICU work environment, and 2) a lack of respect and recognition for the nurses' work. Two themes emerged as major influences on job satisfaction: 1) recognition of work, and 2) professional opportunities and relationships with coworkers. The effects of job satisfaction or dissatisfaction on the nurses' intentions to leave their jobs varied, although three categories were identified. Conclusions: For ICU nurses in China, sources of job dissatisfaction are potentially remedied with simple interventions. Adequate staffing is necessary but not sufficient for a positive work environment. Administrators should address the factors that directly affect their nurses' levels of job satisfaction, as it will ultimately result in less staff turnover and greater patient care.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.