Abstract Ketamine exerts fast acting, robust, and lasting antidepressant effects in a sub-anesthetic dose, however, the underlying mechanisms are still not fully elucidated. Recent studies have ...suggested that ketamine's antidepressant effects are probably attributed to the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The present study aimed to observe the effects of AMPA receptor modulators on mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) expression during the procedure of ketamine exerting antidepressant effects. Therefore, we pretreated rats with NBQX, an AMPA receptor antagonist, or CX546, an AMPA receptor agonist, and subsequently observed the immobility time during the forced swimming test (FST) and the hippocampal and prefrontal cortical levels of mTOR and BDNF. The results showed ketamine decreased the immobility time of rats during the FST and increased the hippocampal and prefrontal cortical mTOR and BDNF. NBQX pretreatment significantly increased the immobility time and decreased the levels of mTOR and BDNF when compared with vehicle 1 (DMSO) pretreatment. CX546 pretreatment significantly decreased the immobility time and increased the levels of mTOR and BDNF when compared with vehicle 2 (DMSO + ethanol) pretreatment. Our results suggest ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.
Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Nitrous acid (HONO) plays a key role in atmospheric chemistry by influencing the budget of hydroxyl radical (OH). In this study, a two-month measurement of HONO and related quantities were analyzed ...during a biomass burning season in 2012 at a suburban site in the western Yangtze River delta, eastern China. An overall high HONO concentration with the mean value of 0.76 ppbv (0.01 ppbv to 5.95 ppbv) was observed. During biomass burning (BB) periods, both HONO concentration and HONO/NO2 ratio were enhanced significantly (more than a factor of 2, p < 0.01) compared with non-biomass burning (non-BB) periods. A correlation analysis showed that the HONO in BB plumes was more correlated with nitrogen dioxide (NO2) than that with potassium (a tracer of BB). Estimation by the method of potassium tracing suggests a maximum contribution of 17 plus or minus 12% from BB emission to the observed HONO concentrations, and the other over 80% of the observed nighttime HONO concentrations during BB periods were secondarily produced by the heterogeneous conversion of NO2. The NO2-to-HONO conversion rate (CHONO) in BB plumes was almost twice as that in non-BB plumes (0.0062 hr-1 vs. 0.0032 hr-1). Given that the residence time of the BB air masses was lower than that of non-BB air masses, these results suggest BB aerosols have higher NO2 conversion potentials to form HONO than non-BB aerosols. A further analysis based on comparing the surface area at similar particle mass levels and HONO/NO2 ratios at similar surface area levels suggested larger specific surface areas and higher NO2 conversion efficiencies of BB aerosols. A mixed plume of BB and anthropogenic fossil fuel (FF) emissions was observed on 10 June with even higher HONO concentrations and HONO/NO2 ratios. The strong HONO production potential (high HONO/NO2 to PM2.5 ratio) was accompanied with a high sulfate concentration in this plume, suggesting a promotion of mixed aerosols to the HONO formation. In summary, our study suggests an important role of BB in atmospheric chemistry by affecting the HONO budget. This can be especially important in eastern China, where agricultural burning plumes are inevitably mixed with urban and industrial pollution.
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Aerosol particles play important roles in regional air quality and global climate change. In this study, we analyzed 2 years (2011–2013) of measurements of submicron particles (6–800 nm) at a ...suburban site in the western Yangtze River Delta (YRD) of eastern China. The number concentrations (NCs) of particles in the nucleation, Aitken and accumulation modes were 5300 ± 5500, 8000 ± 4400, 5800 ± 3200 cm−3, respectively. The NCs of total particles are comparable to those at urban/suburban sites in other Chinese megacities, such as Beijing, but about 10 times higher than in the remote western China. Long-range and regional transport largely influenced number concentrations and size distributions of submicron particles. The highest and lowest accumulation-mode particle number concentrations were observed in air masses from the YRD and coastal regions, respectively. Continental air masses from inland brought the highest concentrations of nucleation-mode particles. New particle formation (NPF) events, apparent in 44 % of the effective measurement days, occurred frequently in all the seasons except winter. The frequency of NPF in spring, summer and autumn is much higher than other measurement sites in China. Sulfuric acid was found to be the main driver of NPF events. The particle formation rate was the highest in spring (3.6 ± 2.4 cm−3 s−1), whereas the particle growth rate had the highest values in summer (12.8 ± 4.4 nm h−1). The formation rate was typically high in relatively clean air masses, whereas the growth rate tended to be high in the polluted YRD air masses. The frequency of NPF events and the particle growth rates showed a strong year-to-year difference. In the summer of 2013, associated with a multi-week heat wave and strong photochemical processes, NPF events occurred with larger frequency and higher growth rates compared with the same period in 2012. The difference in the location and strength of the subtropical high pressure system, which influences the air mass transport pathways and solar radiation, seems to be the cause for year-to-year differences. This study reports, up to now, the longest continuous measurement records of submicron particles in eastern China and helps to achieve a comprehensive understanding of the main factors controlling the seasonal and year-to-year variation of the aerosol size distribution and NPF in this region.
Abstract
Background
Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, ...Hubei.
Aim
This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China.
Design
This study was a retrospective case series.
Methods
Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020.
Results and discussion
Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5–57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3–8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1–2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia.
Conclusions
Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.
Summary
Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon‐γ and is considered as a marker for macrophage activation. This study aimed ...to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty‐two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti‐melanoma differentiation‐associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP‐ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non‐survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non‐survivors and survivors at an optimal cut‐off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan–Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log‐rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092–10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP‐ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.
Serum neopterin was significantly increased in DM, especially in patients with anti‐MDA5 and RP‐ILD. Serum neopterin seems to parallel disease severity in DM patients. High baseline level of neopterin was associated with increased mortality and was identified as an independent prognostic factor in DM.
A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest ...iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.
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