[Analysis of the clinical characteristics and therapeutic effect of refractory juvenile dermatomyositis to tofacitinib].

Objective: To elucidate the clinical features of patients with refractory juvenile dermatomyositis (JDM), and to explore the efficacy and safety of tofacitinib in the treatment of refractory JDM. Methods: A total of 75 JDM patients admitted to the Department of Rheumatology and Immunology in Shenzhen Children's Hospital from January 2012 to January 2021 were retrospectively analyzed, and to analyze the clinical manifestations, efficacy and safety of tofacitinib in the treatment of refractory JDM. Patients were divided into refractory group with using of glucocorticoids in combination with two or more anti-rheumatic drugs for treatment, and the presence of disease activity or steroid dependence after a one-year follow-up. The non-refractory group is defined as clinical symptoms disappeared, laboratory indicators were normal, and clinical remission was achieved after initial treatment, and the clinical manifestations and laboratory indexes of the two groups were compared. The Mann-Whitney U test, Fisher's precision probability test was used for intergroup comparison. Binary Logistic multivariate regression analysis was used to identify risk factors for refractory JDM. Results: Among the 75 children with JDM, 41 were males and 34 were females with a age of onset of 5.3 (2.3, 7.8) years. The refractory group consisted of 27 cases with a age of onset of 4.4 (1.5, 6.8) years, while the non-refractory group consisted of 48 cases with a age of onset of 5.9 (2.5, 8.0) years. Compared with 48 cases in the non-refractory group, the proportion of interstitial lesions and calcinosis in the refractory group was higher than that in the non-refractory group (6 cases (22%) vs. 2 cases (4%), 8 cases (30%) vs. 4 cases (8%), both P<0.05). Binary Logistic regression analysis showed that observation group were more likely to be associated with to interstitial lung disease (OR=6.57, 95%CI 1.22-35.31, P=0.028) and calcinosis (OR=4.63, 95%CI 1.24-17.25, P=0.022). Among the 27 patients in the refractory group, 22 cases were treated with tofacitinib, after treatment with tofacitinib, 15 of 19 cases (86%) children with rashes showed improvement, and 6 cases (27%) with myositis evaluation table score less than 48 score both were improved, 3 of 6 cases (27%) had calcinosis were relieved, and 2 cases (9%) had glucocorticoid-dependence children were successfully weaned off. During the tofacitinib treatment, there was no increase in recurrent infection, blood lipids, liver enzymes, and creatinine were all normal in the 22 cases. Conclusions: Children with JDM with calcinosis and interstitial lung disease are more likely to develop refractory JDM. Tofacitinib is safe and effective for refractory JDM.

Theoretical investigations on the superhydrophobicity of intrinsic hydrophilic surfaces with overhang microstructures.

It has been accepted generally that it is necessary to obtain the so-called surface superhydrophobicity on intrinsically hydrophobic materials. However, recent experiments have indicated that it could be possible to prepare superhydrophobic surfaces on intrinsically hydrophilic materials by creating adequate roughness. In this work, such a strategy for surface superhydrophobicity on hydrophilic materials with an intrinsic contact angle less than 90° was demonstrated thermodynamically based on a proposed 2-D analytical model. In particular, different (trapezoidal, vertical and inverse-trapezoidal) microstructures were employed to analyze their wetting states such as composite and noncomposite and superhydrophobic behavior as well as the previous corresponding experimental observations. Based on the thermodynamic calculations, it was demonstrated that for an overhang microstructure, intrinsic contact angle, which was restricted by the sidewall angle of micropillars, was not an independent parameter to affect superhydrophobicity. Furthermore, an overhang microstructure was critical to realize the transition from hydrophilicity to superhydrophobicity, and for such a transition, the sidewall angle should be less than the intrinsic contact angle where a positive free energy barrier could support the liquid/vapor interfaces and separate the Wenzel and Cassie states on such hydrophilic surfaces. Most importantly, it was found that for such hydrophilic surfaces, generally, the free energy of the noncomposite or Wenzel states were lower than that of the composite or Cassie states for those trapezoidal, vertical and inverse-trapezoidal microstructures, implying that once a noncomposite state was formed, it can hardly become a composite state, or in other words, even if superhydrophobic behavior was possible, it could be temporary or unstable.

Isolation and genetic characterization of a novel adeno-associated virus from Muscovy ducks in China.

Adeno-associated virus (AAV; genus Dependoparvovirus, family Parvoviridae) was first discovered in 1965 as a contaminant in adenovirus preparations. The AAVs are generally considered non-pathogenic, and they have the ability to attenuate the replication of other more pathogenic viruses, which makes them attractive as potential therapeutics or preventative measures. This study characterized a novel AAV isolated from Muscovy ducks in China. The novel virus (MHH-05-2015) was isolated after propagating a field isolate of the DAdV-3 virus (a type 3 duck adenovirus) in duck embryo fibroblasts. The full genome sequence of MHH-05-2015 was determined, and the nucleotide and amino acid sequences were compared to other avian AAVs. The genomic distribution of the structural and non-structural protein-coding genes in MHH-05-2015 was conserved and consistent with the other AAVs. Compared to previously isolated avian AAVs, MHH-05-2015 had approximately 63 to 64% sequence identity. Phylogenetic analysis indicated that MHH-05-2015 clustered separately from other avian AAVs, suggesting that MHH-05-2015 was not directly descended from other Dependoparvovirus family members. These results suggest that MHH-05-2015 is a new subtype of AAV that is distinct from other avian AAVs.

[A cohort study of abnormal routine blood test results in landfill workers].

Objective: To investigate the abnormalities of the blood system in landfill workers. Methods: A cohort study was conducted for 224 landfill workers who were followed up for 6 consecutive years with abnormal routine blood test results and a low platelet count as the outcome events. The life-table method was used to analyze the incidence rates of these two outcome events, and the incidence rates were compared between first-and second-line workers. Results: A total of 71 workers had abnormal routine blood test results, among whom 29 had abnormal leukocyte count, 14 had abnormal erythrocyte count, 40 had abnormal platelet count, 17 had abnormal hemoglobin, and 29 had a reduction in platelet count. For these landfill workers, the 6-year abnormal rate of routine blood test results was 43.2%, and the incidence rate of low platelet count within 6 years was 13.5%. The first-line workers had a significantly lower abnormal rate of routine blood test results than the second-line workers (P=0.020) , and the relative risk of abnormal routine blood test results in the first-and second-line workers was 0.592. There was no significant difference in the incidence rate of low platelet count between the two groups of workers (P≥0.05) . Conclusion: The landfill has an adverse effect on the blood system of landfill workers, and the second-line workers have greater impairment than the first-line workers.

Human umbilical cord mesenchymal stem cells ameliorate experimental cirrhosis through activation of keratinocyte growth factor by suppressing microRNA-199.

OBJECTIVE: Keratinocyte growth factor (KGF) has a demonstrated role in the prevention of cirrhosis during liver regeneration. Previous studies have shown that transplantation of human umbilical cord mesenchymal stem cells (HUCMSCs) reduces the development of cirrhosis after liver injury. However, whether KGF may be involved in the underlying molecular mechanisms remains unknown. Here we addressed this question. MATERIALS AND METHODS: We did HUCMSC transplantation in mice that had developed cirrhosis by carbon tetrachloride (CCl4). The effects of UCMSC transplantation on KGF levels and liver damage were examined. The level of a KGF-targeting microRNA, miR-199, was examined. The regulation of KGF by miR-199 was studied by bioinformatics analyses and luciferase reporter assay. RESULTS: HUCMSC transplantation significantly ameliorated the severity of liver fibrosis, reduced portal hypertension and sodium retention that were induced by CCl4. HUCMSC transplantation significantly increased the levels of KGF in the injured liver, seemingly through suppression of miR-199, which targeted 3'-UTR of KGF mRNA to inhibit its protein translation. CONCLUSIONS: HUCMSCs may ameliorate cirrhosis through activation of KGF by suppressing miR-199.

Commissioning and operation of the deuteron injector for PKUNIFTY project.

PKUNIFTY (PeKing University Neutron Imaging FaciliTY), a thermal neutron imaging facility based on a 2 MeV RFQ accelerator, has been constructed at Peking University. Its deuteron injector, which consists of a 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) deuteron ion source and a two-solenoid low energy beam transport (LEBT), aims at producing and delivering 50 mA, 50 keV deuteron beam with a duty factor of 10% (1 ms, 100 Hz). In the preliminary tests of RFQ accelerator, the ECR ion source and LEBT are required to operate at various duty factors (from 1% to 10%). The deuteron ion source has been tested with different pulse widths for this reason. In order to optimize the transmission parameters, the beam current at the exit of RFQ as a function of solenoids tuning and steering magnets tuning are carefully studied. The beam emittance at the entrance of RFQ has been measured with space charge compensation by different argon gas (RG) pressure from 1.6 × 10(-4) Pa to 4.7 × 10(-3) Pa. The measuring results show the best compensating pressure is 3.5 × 10(-3) Pa with a minimal normalized rms emittance of 0.12 pi mm mrad. During the commissioning, we found the purity of deuteron gas is an important factor which severely affects ECR discharge and plasma intensity inside the ion source chamber. The detailed experimental results obtained during the commissioning are discussed in this paper.

Handling radiation generated during an ion source commissioning.

Radiation is an important issue, which should be carefully treated during the design and commissioning of an ion source. Measurements show that X-rays are generated around the ceramics column of an extraction system when the source is powered up to 30 kV. The X-ray dose increases greatly when a beam is extracted. Inserting the ceramic column into a metal vacuum box is a good way to block X-ray emission for those cases. Moreover, this makes the online test of an intense H(+) ion beam with energy up to 100 keV possible. However, for deuteron ion source commissioning, neutron and gamma-ray radiation become a serious topic. In this paper, we will describe the design of the extraction system and the radiation doses of neutrons and gamma-rays measured at different D(+) beam energy during our 2.45 GHz deuteron electron cyclotron resonance ion source commissioning for PKUNIFTY (PeKing University Neutron Imaging FaciliTY) project at Peking University.

Deuteron injector for Peking University Neutron Imaging Facility project.

The deuteron injector developed for the PKUNIFTY (Peking University Neutron Imaging Facility) has been installed and commissioned at Peking University (PKU). The injector system must transfer 50 keV 50 mA of D(+) ion beam to the entrance of the 2 MeV radio frequency quadrupole (RFQ) with 10% duty factor (1 ms, 100 Hz). A compact 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) ion source and a 1.36 m long low energy beam transport (LEBT) line using two solenoids was developed as the deuteron injector. A φ5 mm four-quadrant diaphragm was used to simulate the entrance of RFQ electrodes. The beam parameters are measured after this core with an emittance measurement unit (EMU) and a bending magnet for ion fraction analysis at the end of injector. During the commissioning, 77 mA of total deuteron beam was extracted from PMECR and 56 mA of pure D(+) beam that passed through the φ5 mm four-quadrant diaphragm was obtained at the position of RFQ entrance with the measured normalized rms emittance 0.12-0.16π mm mrad. Ion species analysis results show that the deuteron fraction is as high as 99.5%. All of the parameters satisfy PKUNIFTY's requirements. In this paper, we will describe the deuteron injector design and report the commissioning results as well as the initial operation.

Intense beams from gases generated by a permanent magnet ECR ion source at PKU.

An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about 120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and 65 mA of He(+) extracted at 50 kV through a φ 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 π mm mrad. Tungsten samples were irradiated by H(+) or He(+) beam extracted from this ion source and H∕He holes and bubbles have been observed on the samples. A method to produce a high intensity H∕He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He(+) beam injector for coupled radio frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He(+) beam.

NOVEL LEAD ZIRCONATE TITANATE COMPOSITE VIA FREEZING TECHNOLOGY FOR HIGH FREQUENCY TRANSDUCER APPLICATIONS.

Novel PZT-5A ceramic-polymer composite was prepared via freezing technology. This composite exhibited good dielectric and ferroelectric behaviors. At 1 kHz, the dielectric constant and the dielectric loss were 546 and 0.046, respectively, while the remnant polarization was 13.0 µC/cm(2) at room temperature. The electromechanical coupling coefficient (k(t)) of PZT-5A composite was measured to be 0.54, which is similar to that of PZT piezoelectric ceramic. The piezoelectric coefficient (d(33)) of PZT-5A composite was determined to be ~250 pC/N. Using this composite, a 58MHz single element transducer with the bandwidth of 70% at -6dB was built, and the insertion loss was tested to be -29dB around the central frequency.

The deuteron injector progress of the Peking University Neutron Imaging Facility project.

A deuteron radio frequency quadrupoles injector h has been developed at Peking University. A permanent magnetic electron cyclotron resonance (ECR) ion source is used in the injector system. A 50 keV 100 mA proton beam has been extracted from the ECR ion source and the measured normalized rms emittance is 0.11-0.14pi mm mrad. A deuteron beam has also been extracted at 50 kV with 83 mA total current and its emittance is less than 0.18pi mm mrad. The proton beam transmission has been investigated on a low energy beam transport test bench, and up to 93% transmission can be reached. The new injector with two solenoids has been designed and is being constructed. All the development results will be presented in this paper.

Upgrade of the extraction system of permanent magnet electron cyclotron resonance ion source.

A set of new ion extraction electrodes have been designed for the permanent magnetic electron cyclotron resonance ion source at Peking University to improve beam quality and transmission. PBGUNS has been used to optimize the extraction electrodes and simulate the beam behavior at the extraction region. The experiments showed that with the new system, the beam half divergence angle can be less than 40 mrad and the normalized rms emittance is about 0.13pi mm mrad when the extracted current is 100 mA at 50 keV in pulse mode. The voltage of the suppression electrode has great effect on beam divergence. The effect of the microwave power and gas flow is also studied.

Multiple matching scheme for broadband 0.72Pb(Mg(13)Nb(23))O(3)-0.28PbTiO(3) single crystal phased-array transducer.

Lead magnesium niobate-lead titanate single crystal 0.72Pb(Mg(13)Nb(23))O(3)-0.28PbTiO(3) (abbreviated as PMN-PT) was used to fabricate high performance ultrasonic phased-array transducer as it exhibited excellent piezoelectric properties. In this paper, we focus on the design and fabrication of a low-loss and wide-band transducer for medical imaging applications. A KLM model based simulation software PiezoCAD was used for acoustic design of the transducer including the front-face matching and backing. The calculated results show that the -6 dB transducer bandwidth can be improved significantly by using double lambda8 matching layers and hard backing. A 4.0 MHz PMN-PT transducer array (with 16 elements) was fabricated and tested in a pulse-echo arrangement. A -6 dB bandwidth of 110% and two-way insertion loss of -46.5 dB were achieved.

Self-separated hydrothermal lead zirconate titanate thick films for high frequency transducer applications.

Using a simple rapid heating process, Pb(Zr(0.52)Ti(0.48))O(3) (PZT) thick films prepared by hydrothermal method were separated from a Ti substrate. Scanning electron microscopy (SEM) revealed that the self-separated films were crack-free. After solution infiltration and high temperature annealing, the PZT thick films were shown to possess good electric properties. At 1 kHz, the dielectric constant and the loss were 593 and 0.05, respectively. The remnant polarization was 30.0 muCcm(2) at room temperature. A high frequency single element ultrasound transducer fabricated with these films showed a bandwidth at -6 dB of 73% at a center frequency of 67 MHz.

Lead-free KNLNT piezoelectric ceramics for high-frequency ultrasonic transducer application.

This paper presents the latest development of a lead-free piezoelectric ceramic and its application to transducers suitable for high-frequency ultrasonic imaging. A lead-free piezoelectric ceramic with formula of (K(0.5)Na(0.5))(0.97)Li(0.03)(Nb(0.9) Ta(0.1))O(3) (abbreviated as KNLNT-0.03/0.10) was fabricated and characterized. The material was found to have a clamped dielectric constant epsilon(33)(S)/epsilon(0)=890, piezoelectric coefficient d(33)=245 pC/N, electromechanical coupling factor k(t)=0.42 and Curie temperature T(c)>300 degrees C. High-frequency (40 MHz) ultrasound transducers were successfully fabricated with the lead-free material. A representative lead-free transducer had a bandwidth of 45%, two-way insertion loss of -18 dB. This performance is comparable to reported performances of popular lead-based transducers. The comparison results suggest that the lead-free piezoelectric material may serve as an alternative to lead-based piezoelectric materials for high-frequency ultrasonic transducer applications.

Self-focused ZnO transducers for ultrasonic biomicroscopy.

A simple fabrication technique was developed to produce high frequency (100 MHz) self-focused single element transducers with sputtered zinc oxide (ZnO) crystal films. This technique requires the sputtering of a ZnO film directly onto a curved backing substrate. Transducers were fabricated by sputtering an 18 µm thick ZnO layer on 2 mm diameter aluminum rods with ends shaped and polished to produce a 2 mm focus or f-number equal to one. The aluminum rod served a dual purpose as the backing layer and positive electrode for the resultant transducers. A 4 µm Parylene matching layer was deposited on the transducers after housing and interconnect. This matching layer was used to protect the substrate and condition the transfer of acoustic energy between the ZnO film and the load medium. The pulse-echo response for a representative transducer was centered at 101 MHz with a -6 dB bandwidth of 49%. The measured two way insertion loss was 44 dB. A tungsten wire phantom and an adult zebrafish eye were imaged to show the capability of these transducers.

Temperature dependence of oriented growth of Pb[Yb(1/2)Nb(1/2)]O(3)-PbTiO(3) thin films deposited on LNO/Si substrates.

(1-x)Pb[Yb(1/2)Nb(1/2)]O(3)-xPbTiO(3) (PYbN-PT, x=0.5)(001) oriented thin films were deposited onto LaNiO3 (LNO)/Si(001) substrates by sol-gel processing. The crystallographic texture of the films was controlled by the annealing temperature and heating rate. Highly (001) oriented LNO thin films were prepared by a simple metal organic decomposition technique, and the samples were annealed at 700 °C and 750 °C using a rapid thermal annealing process and furnace, respectively. X-ray diffraction analysis revealed that the films of PYbN-PT were highly (001) oriented along LNO/Si substrates. The degree of PYbN-PT orientation is dependent on the heating rate and annealing temperature. Annealing heating rate of 10 °C/s and high annealing temperature near 750 °C produce the greatest degree of (001) orientation, which gives rise to improved dielectric properties.

PMN-PT single crystal thick films on silicon substrate for high-frequency micromachined ultrasonic transducers.

In this work, a novel high-frequency ultrasonic transducer structure is realized by using PMNPT-on-silicon technology and silicon micromachining. To prepare the single crystalline PMNPT-on-silicon wafers, a hybrid processing method involving wafer bonding, mechanical lapping and wet chemical thinning is successfully developed. In the transducer structure, the active element is fixed within the stainless steel needle housing. The measured center frequency and -6 dB bandwidth of the transducer are 35 MHz and 34%, respectively. Owing to the superior electromechanical coupling coefficient (k(t)) and high piezoelectric constant (d(33)) of PMNPT film, the transducer shows a good energy conversion performance with a very low insertion loss down to 8.3 dB at the center frequency.

Self-focused ZnO transducers for ultrasonic biomicroscopy.

A simple fabrication technique was developed to produce high frequency (100 MHz) self-focused single element transducers with sputtered zinc oxide (ZnO) crystal films. This technique requires the sputtering of a ZnO film directly onto a curved backing substrate. Transducers were fabricated by sputtering an 18 mum thick ZnO layer on 2 mm diameter aluminum rods with ends shaped and polished to produce a 2 mm focus or f-number equal to one. The aluminum rod served a dual purpose as the backing layer and positive electrode for the resultant transducers. A 4 mum Parylene matching layer was deposited on the transducers after housing and interconnect. This matching layer was used to protect the substrate and condition the transfer of acoustic energy between the ZnO film and the load medium. The pulse-echo response for a representative transducer was centered at 101 MHz with a -6 dB bandwidth of 49%. The measured two way insertion loss was 44 dB. A tungsten wire phantom and an adult zebrafish eye were imaged to show the capability of these transducers.

Piezoelectric PZT thick films on LaNiO(3) buffered stainless steel foils for flexible device applications.

In this paper, we report on 4.5µm piezoelectric Pb(Zr(0.52)Ti(0.48))O(3) (PZT) thick films deposited on flexible stainless steel (SS) foils with LaNiO(3) (LNO) buffer layers using a ceramic powder/sol-gel solution modified composite method. The polycrystalline thick films show a hysteresis loop at an applied electric field of 900 kV cm(-1) with remanent polarization and coercive electric field values of 27µC cm(-2) and 85 kV cm(-1), respectively. At 1 kHz, the dielectric constant is 653 and the dielectric loss is 0.052. The leakage current density of the film is lower than 1.55 × 10(-5) Acm(-2) over the range of 0 to ±150V. The conduction current shows ohmic behaviour at a low electric field and space-charge-limited current characteristics at a high electric field.