Influence of partial cement substitution by ground blast furnace slag on the mechanical properties of phosphogypsum cemented backfill.

Phosphogypsum (PG) stockpiles occupied a large amount of land resources, and serious environmental pollution problems have attracted the attention of countries around the world. Cemented backfill can reduce the environmental problems caused by tailings stockpiles and is an important development trend in green mine construction. To investigate the effect of binder type on the performance of PG cemented backfill, this paper used ground granulated blast furnace slag (GGBFS) to substitute part of Portland cement (PC) as binder and studied the effect of different ratios of binder on the uniaxial compressive strength (UCS), surface crack extension, acoustic emission (AE) characteristics, and microstructure of PG cemented backfill. The results show that substituting part of PC with GGBFS is beneficial to improve the mechanical properties of PG cemented backfill. When PC was substituted by 50% of GGBFS, the 28d UCS of the backfill was increased from 1.535 to 4.539 MPa. Furthermore, the UCS of the backfill gradually increased as the GGBFS substitution level increased, and more AE signals could be monitored during uniaxial compression. Compared with PC, the sulfate in PG participates in the hydration reaction of GGBFS, more hydrated calcium-aluminum-silicate-hydrate (C-A-S-H) gels and ettringite (AFt) are formed, and the microstructure of the backfill is denser, and the required strength can be obtained with less binder. Thus, substituting part PC with GGBFS as a binder can provide an economical and environmentally friendly alternative for the consumption and reuse of large quantities of PG.

Study on mechanical properties and damage characteristics of cemented waste rock-tailing backfill.

Tailing and waste rock-cemented filling is an effective way to solve the problem solid waste in mines. In this paper, the effects of waste rock content and cement-sand ratio on the properties of tailing-waste rock-cemented filling materials and cemented backfill were analyzed based on the single-factor multi-level experimental design method. The results show that with the increase of waste rock content, the fluidity of the filling slurry increases first and then decreases, the bleeding rate increased gradually, and the compressive strength of the backfill increases first and then decreases. When the waste rock content is 60% and the cement-sand ratio is 1:4, the cemented backfill has higher compressive strength. With the increase of waste rock content, the interface failure area between waste rock particles and cementitious matrix under loading gradually increases, the crack extension is more complex, and the acoustic emission (AE) ringing count is higher. Microstructural analysis showed that the main hydration products in the cemented backfill were calcium silicate hydrated (C-S-H) gels, ettringite (AFt), and calcium hydroxide (Ca(OH)2). Because there is more content of hydration products, the microstructure of the cemented backfill was denser and the compressive strength was higher. Based on the results of uniaxial compression tests, the damage constitutive model of cemented backfill with different waste rock contents and cement-sand ratios was established, which could provide guidance for the design and safety production of phosphate rock filling engineering.

Altered Functional Connectivity Strength in Distinct Brain Networks of Children With Early-Onset Schizophrenia.

BACKGROUND: Schizophrenia is regarded as a brain network or connectome disorder that is associated with neurodevelopment. Children with early-onset schizophrenia (EOS) provide an opportunity to evaluate the neuropathology of schizophrenia at a very early stage without potential confounding factors. But dysfunction in brain networks of schizophrenia is inconsistent. PURPOSE: To identify abnormal functional connectivity (FC) in EOS patients and relationships with clinical symptoms, we aimed to reveal neuroimaging phenotypes of EOS. STUDY TYPE: Prospective, cross-sectional. POPULATION: Twenty-six female/22 male patients (age:14.3 ± 3.45 years) with first-episode EOS, 27 female/22 male age- and gender-matched healthy controls (HC) (age:14.1 ± 4.32). FIELD STRENGTH/SEQUENCE: 3-T, resting-state (rs) gradient-echo echo-planar imaging and three-dimensional magnetization-prepared rapid gradient-echo imaging. ASSESSMENT: Intelligence quotient (IQ) was measured by the Wechsler Intelligence Scale-Fourth edition for Children (WISC-IV). The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). FC strength (FCS) from rs functional MRI (rsfMRI) was used to investigate functional integrity of global brain regions. In addition, associations between regionally altered FCS and clinical symptoms in EOS patients were examined. STATISTICAL TESTS: Two-sample t-test controlling for sample size, diagnostic method, brain volume algorithm, and age of the subjects, Bonferroni correction, Pearson's correlation analysis. A P-value <0.05 with a minimum cluster size of 50 voxels was considered statistically significant. RESULTS: Compared with HC, EOS patients had significantly lower total IQ scores (IQ:91.5 ± 16.1), increased FCS in the bilateral precuneus, left dorsolateral prefrontal cortex, left thalamus, and left parahippocampus (paraHIP), and decreased FCS in the right cerebellum posterior lobe and right superior temporal gyrus. The PANSS total score of EOS patients (PANSS total score:74.30 ± 7.23) was found to be positively correlated to FCS in the left paraHIP (r = 0.45). DATA CONCLUSION: Our study revealed that disrupted FC of brain hubs illustrate multiple abnormalities in brain networks in EOS patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

Deformation failure and acoustic emission characteristics of continuous graded waste rock cemented backfill under uniaxial compression.

In order to study the effect of backfill aggregate particle size on the compressive strength and failure mode of cemented backfill, uniaxial compression tests were carried out on seven kinds of cemented backfills with different particle size gradations. By analyzing the AE characteristics during the failure process of the backfill, the damage evolution mechanism of the cemented backfill with different particle size gradations was discussed. The test results show that with the increase of the Talbot gradation index n, the compressive strength of the backfill specimens first increases and then decreases, and the failure mode gradually changes from shear failure to tensile failure. With the increase of particle size gradation, the particle size of aggregate increases, the interface between aggregate and cement matrix is more likely to be fractured, and the characteristic parameters of acoustic emission are more active. During the failure process of backfill, the AE energy rate increases rapidly in the plastic development stage, and reaches maximum value before and after the peak stress, which can be used as the precursor to judge the failure of waste rock cemented backfill. According to the test results, the damage model and constitutive equations of waste rock cemented backfill with different Talbot particle size gradations are established, which can provide engineering guidance for filling mined-out areas with waste rock to ensure safe production of mines.

Notch1/Hes1­PTEN/AKT/IL­17A feedback loop regulates Th17 cell differentiation in mouse psoriasis­like skin inflammation.

IL­17A, the effector cytokine of T helper (Th) 17 cells, plays a crucial role in the pathogenesis of psoriasis. The Notch1 and PI3K/AKT signaling pathways are implicated in Th17 cell differentiation and IL­17A production. The present study aimed to evaluate the regulatory effect of the Notch1/hairy and enhancer of split 1 (Hes1)­PTEN/AKT/IL­17A feedback loop on Th17 cell differentiation via the PI3K/AKT inhibitor LY294002 in a mouse model of psoriasis. Mice were randomly divided into 3 groups: a control group, a model group [5% imiquimod (IMQ)­induced group] and an intervention group (5% IMQ­induced plus LY294002­treated group). Skin structural characteristics were recorded and evaluated by hematoxylin and eosin staining. The weights of the spleens and inguinal lymph nodes were measured. Th17 cell percentage, as well as the mRNA and protein expression levels of Notch1, Notch1 intracellular domain (NICD1), Hes1, PTEN, AKT, phosphorylated (p)­AKT, mTOR complex 1 (mTORC1), p­mTORC1, S6 kinase (S6K)1, S6K2 and IL­17A were detected in skin samples of the three experimental groups. Additionally, splenic mononuclear cells from model mice were treated by 10 and 50 µM LY294002 to further evaluate its regulatory effect on Notch1/Hes1­PTEN/AKT/IL­17A feedback loop. Increased Th17 cell percentage, increased expression of Notch1, NICD1, Hes1, AKT, p­AKT, mTORC1, p­mTORC1, S6K1, S6K2 and IL­17A, and decreased PTEN levels were observed in model mice alongside marked psoriasis­like skin inflammation, splenomegaly and lymphadenopathy. LY294002 treatment significantly alleviated the severity of psoriasis­like skin inflammation in the intervention mice, attenuated the degree of epidermal hyperplasia and dermal inflammatory cell infiltration, and mitigated splenomegaly and lymphadenopathy. In addition, LY294002 treatment reversed the increased Th17 cell percentage, as well as the increased expression of Notch1, NICD1, Hes1, AKT, p­AKT, mTORC1, p­mTORC1, S6K1, S6K2 and IL­17A, and the decreased expression of PTEN. In vitro study from 5% IMQ­induced mouse splenic mononuclear cells presented that high dose of LY294002 exerted more obviously regulatory effect on Notch1/Hes1­PTEN/AKT/IL­17A feedback loop. The current findings suggested that the Notch1/Hes1­PTEN/AKT/IL­17A feedback loop regulates Th17 cell differentiation within the disease environment of psoriasis. Blocking the Notch1/Hes1­PTEN/AKT/IL­17A feedback loop may thus be a potential therapeutic method for management of psoriatic inflammation.

Review of 52 cases with Hailey-Hailey disease identified 25 novel mutations in Chinese Han population.

Hailey-Hailey disease (HHD) is a rare autosomal dominant inherited keratosis caused by mutations in ATP2C1. The aim of our study was to identify and analyze the features of the mutations in HHD. We examined 52 Chinese Han cases which were diagnosed as HHD based on their clinical and histological findings. Genomic DNA polymerase chain reaction and direct sequencing of ATP2C1 were performed from peripheral blood samples of the patients and 100 unrelated healthy controls. Twenty-five novel mutations and 14 recurrent mutations were identified, including 11 (28.2%) missense mutations, nine (23.1%) frame-shift deletion mutations, eight (20.5%) nonsense mutations, seven (17.9%) splicing mutations and four (10.3%) frame-shift insertion mutations. Together with ours, all 209 mutations showed a uniform distribution without hotspots or clusters. In addition, there is no specific genotype-phenotype correlation in HHD. Our findings update the spectrum of mutations in ATP2C1.

Seroprevalence and associated factors of HSV-2 infection among general population in Shandong Province, China.

BACKGROUND: Herpes simplex virus type-2 (HSV-2) infection is the main cause of genital ulcer disease and increases the risk of HIV acquisition. Little information is available regards the epidemiological characteristics of HSV-2 among general population in China. The aim of this study was to explore seroprevalence and associated factors of HSV-2 and provide information for design of HSV-2 control strategy in Shandong, China. METHODS: In this cross-sectional study, a total of 8074 persons, 18-49 years of age, were selected using multi-stage probability sampling to represent the general population of Shandong in 2016. Demographic data were collected through face-to-face interviews. Other variables were obtained by self-administered questionnaire surveys. Blood was collected for HSV-2 IgG detection with ELISA. RESULTS: A total of 7256 sexually-active participants were included in the analysis. The weighted seroprevalence of HSV-2 infection was 4.2% (95% confidence interval [CI], 3.2-5.3) in females, which was significant higher than that in males (2.7%; 95% CI, 1.1-4.2) (P = 0.04). The seroprevalence of HSV-2 was higher in individuals from eastern region (6.4%; 95% CI, 5.9-6.9) and urban areas (4.3%; 95% CI, 2.6-6.0) of Shandong than those from other regions (P < 0.01). Associated factors for HSV-2 infection among men were being urban residents (adjusted odds ratio [AOR], 2.36; 95% CI, 1.14-4.88), having two or more sex partners in the past year (AOR, 3.22; 95% CI, 1.90-5.43) and having commercial sex (AOR, 1.51; 95% CI, 1.00-2.26). Among females, being divorced or widowed (AOR, 1.79; 95% CI, 1.08-2.97), having a tattoo (AOR, 2.89; 95% CI, 1.07-7.84), and being dissatisfied with the sex activity quality (AOR, 2.12; 95% CI, 1.24-3.63) was associated with HSV-2 infection. CONCLUSIONS: This study showed a relatively low burden of HSV-2 in Shandong province, China compared with the seroprevalence reported in many other provinces and countries. HSV-2 control programs in Shandong should focus on eastern, urban and female residents, and pay more attention to individuals with identified associated factors.

Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy.

Importance: Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. Objective: To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. Design, Setting, and Participants: A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. Exposures: Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. Main Outcomes and Measures: The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. Results: Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. Conclusions and Relevance: Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

Development and evaluation of a droplet digital PCR assay for the diagnosis of paucibacillary leprosy in skin biopsy specimens.

BACKGROUND: The reduced amounts of Mycobacterium leprae (M. leprae) among paucibacillary (PB) patients reflect the need to further optimize methods for leprosy diagnosis. An increasing number of reports have shown that droplet digital polymerase chain reaction (ddPCR) is a promising tool for diagnosis of infectious disease among samples with low copy number. To date, no publications have investigated the utility of ddPCR in the detection of M. leprae. The aim of this study was to develop and evaluate a ddPCR assay for the diagnosis of PB leprosy. METHODOLOGY: The two most sensitive DNA targets for detection of M. leprae were selected from electronic databases for assessment of sensitivity and specificity by quantitative polymerase chain reaction (qPCR) and ddPCR. Control patients (n = 59) suffering from other dermatological diseases were used to define the cut-off of the duplex ddPCR assay. For comparative evaluation, qPCR and ddPCR assays were performed in 44 PB patients and 68 multibacillary (MB) patients. PRINCIPAL FINDINGS: M. leprae-specific repetitive element (RLEP) and groEL (encoding the 65 kDa molecular chaperone GroEL) were used to develop the ddPCR assay by systematically analyzing specificity and sensitivity. Based on the defined cut-off value, the ddPCR assay showed greater sensitivity in detecting M. leprae DNA in PB patients compared with qPCR (79.5% vs 36.4%), while both assays have a 100% sensitivity in MB patients. CONCLUSIONS/SIGNIFICANCE: We developed and evaluated a duplex ddPCR assay for leprosy diagnosis in skin biopsy samples from leprosy patients. While still costly, ddPCR might be a promising diagnostic tool for detection of PB leprosy.

Prevalence, risk factors, and medical costs of Chlamydia trachomatis infections in Shandong Province, China: a population-based, cross-sectional study.

BACKGROUND: A population-based study of Chlamydia trachomatis (CT) infections is essential in designing a specific control program; however, no large investigation of CT infections among the general population in mainland China has been conducted since 2000. We aimed to determine the prevalence, risk factors, and associated medical costs of CT among residents, 18-49 years of age, in Shandong, China. METHODS: From May to August 2016, a multistage probability sampling survey involving 8074 individuals was distributed. Data were collected via face-to-face interviews, followed by self-administered questionnaire surveys. First-void urines were collected and tested for CT and Neisseria gonorrhoeae (NG) using nucleic acid amplification. RESULTS: The weighted prevalence of CT infection was 2.3% (95% confidence interval [CI], 1.5-3.2) in females and 2.7% (1.6-3.8) in males. Women, 30-34 years of age, had the highest prevalence of CT infections (3.5%, 2.6-4.4), while the highest prevalence of CT infections in males was in those 18-24 years of age (4.3%, 0.0-8.8). Neisseria gonorrhoeae infection had a prevalence of 0.1% (0.0-0.3) in women and 0.03% (0.0-0.1) in men. Risk factors for CT infections among females included being unmarried, divorced, or widowed (odds ratio [OR], 95% CI 3.57, 1.54-8.24) and having two or more lifetime sex partners (3.72, 1.14-12.16). Among males, first intercourse before 20 years of age (1.83, 1.10-3.02) and having two or more lifetime sex partners (1.85, 1.14-3.02) were associated with CT infections. The estimated lifetime cost of CT infections in patients 18-49 years of age in Shandong was 273 million (range, 172-374 million) China Renminbi in 2016. CONCLUSIONS: This study demonstrated a high burden of CT infections among females < 35 years of age and males < 25 years of age in Shandong. Thus, a CT infection control program should focus on this population, as well as others with identified risk factors.