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To examine the relationship between the therapeutic effect of intratympanic methylprednisolone perfusion and histone acetylation in refractory sudden sensorineural hearing loss.
Thirty-four refractory sudden sensorineural hearing loss patients were enrolled and treated with intratympanic methylprednisolone perfusion. Pure tone average, acetylated histone H3, acetylated histone H4 and histone deacetylase 2 (HDAC2) were measured in peripheral blood mononuclear cells before and after intratympanic methylprednisolone perfusion. Sixteen healthy volunteers were recruited to obtain normal reference values.
Pure tone average in sudden sensorineural hearing loss patients improved from 84.14 ± 13.54 dB to 73.56 ± 18.45 dB after intratympanic methylprednisolone perfusion. Up-regulations in HDAC2 protein level, and down-regulations in histone H3 and H4 acetylation were observed in the intratympanic methylprednisolone perfusion sensitive group (pure tone average gain of 15 dB or more), while no significant changes were observed in the intratympanic methylprednisolone perfusion insensitive group (pure tone average gain of less than 15 dB).
Intratympanic methylprednisolone perfusion can improve hearing in a considerable number of refractory sudden sensorineural hearing loss patients. The therapeutic effect is closely related to reduced histone acetylation.
Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a common pest in sericulture and has developed resistance to different insecticides. However, the mechanisms involved in insecticide resistance of G. pyloalis are poorly understood. Here, we present the first whole-transcriptome analysis of differential expression genes in insecticide-resistant and susceptible G. pyloalis. Clustering and enrichment analysis of DEGs revealed several biological pathways and enriched Gene Ontology terms were related to detoxification or insecticide resistance. Genes involved in insecticide metabolic processes, including cytochrome P450, glutathione S-transferases and carboxylesterase, were identified in the larval midgut of G. pyloalis. Among them, CYP324A19, CYP304F17, CYP6AW1, CYP6AB10, GSTs5, and AChE-like were significantly increased after propoxur treatment, while CYP324A19, CCE001c, and AChE-like were significantly induced by phoxim, suggesting that these genes were involved in insecticide metabolism. Furthermore, the sequence variation analysis identified 21 single nucleotide polymorphisms within CYP9A20, CYP6AB47, and CYP6AW1. Our findings reveal many candidate genes related to insecticide resistance of G. pyloalis. These results provide novel insights into insecticide resistance and facilitate the development of insecticides with greater specificity to G. pyloalis.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
The Chinese white pine beetle Dendroctonus armandi (Coleoptera: Scolytinae) typically displays bivoltinism at altitudes below 1700 m in the Qinling Mountains, China. The periods of host colonization and larval overwintering are two important phases in the life cycle of bark beetles, as it is during these periods that they have to contend with host plant defences and periods of intense cold, respectively. Although during different seasons, the females and males of Chinese white pine beetles show varying tolerances to host plant terpenoids, the sex ratio and survival physiology condition of the two beetle generations are unknown. We investigated the sex ratio of individuals, and also examined the body mass, energy stores, and detoxication enzymes of males and females in each of the two generations in order to determine the overall population stability of each generation. We identified a female-biased sex ratio among adults in both generations. Furthermore, patterns of body mass, energy stores, and detoxication enzymes were found to differ between the two sexes and two seasons. Compared with the males, the females have a larger body mass and higher amounts of stored lipids, which are assumed to be adaptations designed to overcome host resistance and facilitate subsequent oviposition.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.
Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is a new outbreak pest in China. Consequently, it is unclear whether the emergence and spread of the outbreak of this pest are triggered by rapid in situ population size increases in each outbreak area, or by immigrants from a potential source area in China. In order to explore the outbreak process of this pest through a population genetics approach, we developed ten novel polymorphic expressed sequence tags (EST)-derived microsatellites. These new microsatellites had moderately high levels of polymorphism in the tested population. The number of alleles per locus ranged from 3 to 19, with an average of 8.6, and the expected heterozygosity ranged from 0.269 to 0.783. A preliminary population genetic analysis using these new microsatellites revealed a lack of population genetic structure in natural populations of A. lepigone. The estimates of recent migration rate revealed strong gene flow among populations. In conclusion, our study developed the first set of EST-microsatellite markers and shed a new light on the population genetic structure of this pest in China.
A new method, called Cloud of Points (COP) Reconstruction, is proposed in the present work to extend the meshfree method to simulate viscous flows. With the characters of viscous flows, the anisotropic COP structure is distributed in boundary layer. The proposed method can improve the anisotropic COP structure to isotropic COP structure and reduce the condition number of the least square coefficient matrix for conventional meshfree method. The values of the new reconstructed points are calculated by the Lagrange interpolation. The accuracy and the robustness of the presented meshfree solver are demonstrated on a number of standard test cases, including the functions with analytical gradients and the viscous flows past NACA0012 airfoil. The comparison of the simulation results with the experimental data and other numerical simulation data are also investigated.
This study aimed to examine the effectiveness of intratympanic methylprednisolone perfusion as salvage treatment for profound idiopathic sudden sensorineural hearing loss.
A retrospective clinical study of 97 patients with unilateral profound idiopathic sudden sensorineural hearing loss was performed. In all, 83 patients who received salvage intratympanic methylprednisolone perfusion plus conventional treatment (except for steroids) as the second-line therapy were assigned to the study group, while 14 patients who received conventional treatment alone were assigned to the comparison group.
In the study group, treatments in patients with a shorter interval from disease onset to intratympanic methylprednisolone perfusion (up to 15 days) had significantly greater improvements in the overall effective rate and pure tone average compared with patients with a longer interval (over 15 days). For patients with a short interval from disease onset to intratympanic methylprednisolone perfusion, those in the study group had significantly greater improvements in the overall effective rate and pure tone average compared with those in the comparison group. In both the study and comparison groups, hearing improvements were greater at low frequencies than at medium and high frequencies.
The interval from disease onset to intratympanic methylprednisolone perfusion was the major factor affecting hearing recovery. Early second-line salvage intratympanic methylprednisolone perfusion significantly improved the degree of hearing recovery in profound idiopathic sudden sensorineural hearing loss patients after failure of systemic steroid treatment.
Rural-to-urban migrant workers are a large marginalised population in urban China. Prevalence estimates of common mental health problems (CMHPs) in previous studies varied widely and very few studies have investigated migration-related factors of CMHPs in migrant workers. The objective of this study was to determine the prevalence and risk factors of CMHPs among Chinese migrant workers.
A random sample of 3031 migrant workers of ten manufacturing factories in Shenzhen, China, completed a standardised questionnaire containing socio-demographic and migration-related variables and the Chinese 12-item General Health Questionnaire (GHQ-12). A GHQ-12 score of three or higher was used to denote the presence of CMHPs.
The prevalence of CMHPs was 34.4% in Chinese migrant workers. In multiple logistic regression, risk factors for CMHPs included being 16–25 years old (odd ratio [OR] 1.65, 95% confidence interval [CI] 1.28, 2.12), being 26–35 years old (OR 1.36, 95% CI: 1.05, 1.75), low monthly income (OR 1.42, 95% CI 1.04, 1.92), poor living condition (OR: 1.76, 95% CI: 1.22, 2.54), physical illness in the past 2 weeks (OR 1.72, 95% CI 1.43, 2.05), having worked in many cities (OR 1.34, 95% CI 1.03, 1.74), infrequently visiting hometown (OR 1.56, 95% CI 1.22, 1.99), poor Mandarin proficiency (OR 1.51, 95%CI 1.13, 2.01), a low level of perceived benefits of migration (OR 1.33, 95% CI 1.14, 1.55) and working more than 8 h/day (OR 1.39, 95% CI 1.14, 1.70).
CMHPs are very prevalent among Chinese migrant workers. Given the large number of Chinese migrant workers, there is an urgent need to address the mental health burden of China's migrant worker population.
The peaks and dips in the quasar redshift distribution seem to be incompatible with the cosmological principle. This lays the cosmological redshift hypothesis under suspicion and censure, and has been considered by some investigators as a manifestation of the intrinsic nature of quasar's redshift. So it is worthwhile studying whether the redshift distribution of quasars could be explained in the framework of cosmological redshift. As we know, this distribution is affected not only by the possible physical origin of redshift but also by the selection effects in the observations (Zhou, Deng, Zhou 1983). From this we have the redshift distribution function
f(z) = P(z)R(z),
where P(z) is the real distribution function which depends on the evolutionary properties of quasars and the space-time structure of the Universe, and R(z) is the factor caused by the selection effect in the line identification.
Forty-five tree rings (1881–1925) were taken from a white spruce grown near Campbell River in Mackenzie Delta, Canada, for the measurement of 14C activity variation. Because of the narrowness of the rings, 2 and sometimes 3 rings were combined to yield a total of 21 specimens. The 14C content in these specimens was measured with a liquid scintillation-PM tube counter system of the History Department of Peking University. The data points exhibit a 10‰ variation, anti-correlated with sunspot numbers. The physical implication is discussed.
We measured the Δ14C values in 57 rings (from AD 1824 to 1880) of a white spruce grown in Mackenzie Delta (68°N, 130°W), as part of our continuing study of the Δ14C variation related to solar activities. The values exhibit a 10‰ fluctuation with an 11-year periodicity anti-correlated with the solar activity cycle. We also measured the Δ14C values in 6 rings (from AD 1940 to 1945). The abnormally high value in the 1943 ring may be due to two large solar flares occurring in 1942.
The 14C content in 1961–1967 and 1970–1983 tree rings of a spruce grown in Dailing, China (47°N, 129°E) was measured by liquid scintillation. As a result of USSR bomb tests at Novaya Zemlya (72°N, 53°E), Δ14C values rose dramatically from 250‰ in 1961 to a maximum 909‰ in 1964, and then gradually decreased to 238‰ in 1983. We compared Δ14C values in the rings of an oak tree grown at 43°N, 74°W and that of a pine grown at 49°N, 9°E, and atmospheric Δ14C values in both northern and southern hemispheres. We observe that: 1) annual tree rings grown in the same latitude zone have the same Δ14C values, reflecting rapid longitudinal mixing of the atmosphere; 2) atmospheric 14C concentrations reached a global equilibrium distribution at the end of 1968, and tree ring 14C content reflects atmospheric 14C concentration; 3) 1976–1982 rings of the Dailing spruce show excessive 14C, likely due to the effect of 1976 and 1980 Chinese bomb tests; 4) Δ14C decreases exponentially, halving every 17 yr.
The 14C content in 1961–1967 rings of each of three spruce pines grown at (68° N, 130° W), (47° 30' N, 129° 16' E) and (27° 13' N, 100° 20' E) were measured. Δ14C values of the three specimens rise dramatically from a common level (∼250‰) in 1961 to their respective maxima, 964‰, 909‰, and 743‰ in 1964 and then fall to a common level ∼680‰ in 1967. The observed Δ14C increase comes most likely from the nuclear bomb test of the USSR at 75° N in 1961, although there were many other tests since the 1950s. The different effects at different latitudes reflect the atmospheric circulation patterns in the stratosphere and the transport of 14C nuclei from the stratosphere to the troposphere.
The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive insect pest of a wide range of fruits and vegetables. This pest is an invasive species and is currently distributed in some provinces of China. To recover the symbiotic bacteria of B. dorsalis from different invasion regions in China, we researched the bacterial diversity of this fruit fly among one laboratory colony (Guangdong, China) and 15 wild populations (14 sites in China and one site in Thailand) using DNA-based approaches. The construction of 16S rRNA gene libraries allowed the identification of 24 operational taxonomic units of associated bacteria at the 3% distance level, and these were affiliated with 3 phyla, 5 families, and 13 genera. The higher bacterial diversity was recovered in wild populations compared with the laboratory colony and in samples from early term invasion regions compared with samples from late term invasion regions. Moreover, Klebsiella pneumoniae and Providencia sp. were two of the most frequently recovered bacteria, present in flies collected from three different regions in China where B. dorsalis is invasive. This study for the first time provides a systemic investigation of the symbiotic bacteria of B. dorsalis from different invasion regions in China.
The interaction of a relativistic fireball with its ambient medium is described through two shocks: a reverse shock that propagates into the fireball, and a forward shock that propagates into the medium. We here study very early afterglows from the reverse and forward shocks in winds. An optical flash arises from both the relativistic reverse and forward shock while a radio flare is produced by the forward shock.
We investigate whether the circum-burst environment constrained by the absorption feature of GRB990705 could be consistent with the observed H-band afterglow. Two possible geometries of the afterglow-emitting regions are suggested: 1) afterglow emission produced by the impact of the fireball on the surrounding torus; 2)afterglow emission produced in the dense circum-burst medium inside the torus. In case 1), the faster decay at later time is attributed to the disappearance of the shock due to the counter-pressure in the hot torus illuminated by the burst and afterglow photons. For case 2), the circum-burst medium density is found to be very high (n ≳ 104 − 105cm−3).
Based on a refined dynamical model, afterglows from jetted γ-ray burst (GRB) remnants are investigated numerically. Measuring of GRB beaming by using orphan afterglow surveys is addressed. The possible existence of a kind of cylindrical jets is also discussed.