One-neutron stripping process between^(6)Li and^(209)Bi was studied at 28,30,and 34 MeV using the in-beamγ-ray spectroscopy method.Theγ-γcoincident analysis clearly identified twoγ-rays feeding the ground and long...One-neutron stripping process between^(6)Li and^(209)Bi was studied at 28,30,and 34 MeV using the in-beamγ-ray spectroscopy method.Theγ-γcoincident analysis clearly identified twoγ-rays feeding the ground and long-lived isomeric states,which were employed to determine the cross section.The one-neutron stripping cross sections were similar to the cross sections of complete fusion in the^(6)Li+^(209)Bi system,but the one-neutron stripping cross sections decreased more gradually at the sub-barrier region.A coupled-reaction-channel calculation was performed to study the detailed reaction mechanism of the one-neutron stripping process in^(6)Li.The calculations indicated that the first excited state of 5 Li is critical in the actual one-neutron transfer mechanism,and the valence proton of 209Bi can be excited to the low-lying excited state in(^(6)Li,^(5)Li)reaction,unlike in the(d,p)reaction.展开更多
Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datas...Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.展开更多
Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model ...Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection injury.We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually decreased.To investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord tissue.We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury.Qualitative observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co rd.Additionally,transmission electron microscopy showed that axon and myelin sheath morphology was restored.Silencing serum response factor had the opposite effects of ove rexpression.These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury.The underlying mechanism may be related to the regulation of axonal regeneration.展开更多
Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologou...Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna.Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage,12 and 36 hours after subarachnoid hemorrhage.Compared with the controls,atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage,neurological function had clearly improved;brain edema was remarkably relieved;cell apoptosis was markedly reduced in the cerebral cortex of rats;the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only.The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated.The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage.However,these were contrary to the results of 3-methyladenine injection,which inhibits the signaling pathway of autophagy.These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy.The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University,China(904 Hospital of Joint Logistic Support Force of PLA;approval No.YXLL-2017-09)on February 22,2017.展开更多
A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles wou...A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles would settle down under the force of gravity.High volume fraction(50%)particle reinforced AZ91 composites could be easily obtained via this novel method.This is difficult to achieve for other traditional liquid fabrication methods.In addition,there was a good dispersion of TC4 particles in the AZ91 matrix and no clusters were found,which indicate that this method was feasible.Interfacial reaction occurred and the reaction product was confirmed to be Al2Ti.Three kinds of pre-dispersion technologies were used before the settling process and different interfacial microstructures were found.Theoretical calculation and experimental results both indicated that the interfacial product which was embedded in the matrix strengthened the composites and improved the tensile strength.展开更多
Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV ...Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV to 111 MeV. It is a powerful and hopeful researchplatform to reveal the underlying physics of the nuclear, the basic particles and the vacuum or to check the exist basic physical models, quantumelectrodynamic (QED) theories. In the platform, a 1.064 mm Nd:YAG laser system and a 10.6 mm CO_(2) laser system are employed. All the triggersignals to the laser system and the electron control system are from the only reference clock at the very beginning of the LINAC to make sure thetemporal synchronization. Two optical transition radiation (OTR) targets and two charged-couple devices (CCD) are used to monitor and to alignthe electron beam and the laser beam. With the LCS gamma-ray source, it is proposed to experimentally check the gamma-ray calibrations, thephoton-nuclear physics, nuclear astrophysics and some basic QED phenomena.展开更多
Given the challenges facing the cyberspace of the nation, this paper presents the tripartite theory of cyberspace, based on the status quo of cyberspace. Corresponding strategies and a research architecture are propos...Given the challenges facing the cyberspace of the nation, this paper presents the tripartite theory of cyberspace, based on the status quo of cyberspace. Corresponding strategies and a research architecture are proposed for common public networks (C space), secure classified networks (S space), and key infras- tructure networks (K space), based on their individual characteristics. The features and security require- ments of these networks are then discussed. Taking C space as an example, we introduce the SMCRC (which stands for "situation awareness, monitoring and management, cooperative defense, response and recovery, and countermeasures and traceback") loop for constructing a cyberspace security ecosys- tem. Following a discussion on its characteristics and information exchange, our analysis focuses on the critical technologies of the SMCRC loop. To obtain more insight into national cyberspace security, special attention should be paid to global sensing and precise mapping, continuous detection and active manage- ment, cross-domain cooperation and systematic defense, autonomous response and rapid processing, and accurate traceback and countermeasure deterrence.展开更多
Finite element analysis(FEA) method was employed to perform three-dimensional(3D) electric field simulations for gas detectors with multiple wire electrodes.A new element refinement method developed for use in conjunc...Finite element analysis(FEA) method was employed to perform three-dimensional(3D) electric field simulations for gas detectors with multiple wire electrodes.A new element refinement method developed for use in conjunction with the FEA program ANSYS allows successful meshing of the wires without physically inputting the wires in the chamber geometry. First, we demonstrate a model with only one wire, for which we calculate the potential distributions on the central plane and the end-cap region. The results are compared to the calculations obtained using GARFIELD, a two-dimensional program that uses the nearly exact boundary element method. Then we extend the method to same model, but with seven wires.Our results suggest that the new method can be applied easily to the 3D electric field calculations for complicated gas detectors with many wires and complicated geometry such as multiwire proportional chambers and time projection chambers.展开更多
Objective:The ongoing coronavirus disease 2019(COVID-19)epidemic has caused extensive damage worldwide.We explored whether the medical care conduct of patients with psoriasis has changed and whether the COVID-19 epide...Objective:The ongoing coronavirus disease 2019(COVID-19)epidemic has caused extensive damage worldwide.We explored whether the medical care conduct of patients with psoriasis has changed and whether the COVID-19 epidemic has placed more psychological pressure on these patients.Methods:A questionnaire survey was administered to patients with psoriasis in the Dermatology Department of Peking University Third Hospital in July 2022.Information about the patients’general demographics,psoriasis condition,mental state of anxiety(Generalized Anxiety Disorder-7[GAD-7]score),changes in medical care conduct,and Concerns about COVID-19-Related Risk Score for Psoriasis(CCRSP,a self-designed questionnaire)was collected.Univariate analysis with the Mann-Whitney U test for continuous variables was used in the estimation of statistical differences.Results:A total of 112 patients with psoriasis completed the survey.Purchasing medicine was the factor that added difficulty for most participants(32.1%).Fewer participants(26.8%)encountered medical registration difficulties than economic and transportation difficulties.Nearly three-quarters of participants(73.2%)reported at least one medical care conduct change resulting from the COVID-19 epidemic.A small proportion of participants(12.5%)thought that COVID-19 prevented them from seeking medical services for psoriasis.The top three items that caused the most concern were psoriasis aggravation resulting from drug reduction and withdrawal because of COVID-19(44.7%),psoriasis aggravation after infection with COVID-19(38.4%),and psoriasis-related side effects of the COVID-19 vaccine(35.7%).The GAD-7 score of patients with a high CCRSP(score of>10)was significantly higher than that of patients with a low CCRSP(score of≤10)(nonparametric test,P=0.047).Conclusion:COVID-19 poses challenges and places a mental burden on patients with psoriasis.Doctors should regulate the medical behavior of patients with psoriasis according to their specific COVID-19 situation and help patients ease their anxiety to maintain the stability of their psoriasis condition.展开更多
Background: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the...Background: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the treatment of psoriasis in vitro and in vivo. Methods: HaCaT cells were treated with matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay was used to assess the growth and proliferation of HaCaT cells. Cell cycle and apoptosis were detected by flow cytometry. Expression of protein was detected by Western blotting. Autophagy was observed by transmission electron microscopy. Then HaCaT cells were assigned to normal saline (NS) control group, matrine (0.4 mg/mL) group, acitretin (10 μmol/L) group, and matrine plus acitretin group, and the above methods were repeated. In animal experiments, the cumulative score (erythema, scaling, thickening) as a measure of the severity of inflammation was used to measure the skin performance of mice after treated with matrine 50 mg/kg, acitretin 4.5 mg/kg or combination of the two drugs on the psoriasis-like mouse models, respectively. Pathological findings of the lesions were observed, and the protein expressions in the lesions were detected by immunohistochemistry. Results: Cell proliferation inhibition was seen in HaCaT cells with treatment of matrine in a dose- and time-dependent manner (P < 0.01, respectively). Cell cycle G0/G1 phase arrest was observed in a dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and Beclin 1 (P < 0.01) increased and the expression of cyclin D1 (P < 0.05) decreased with increasing doses of matrine. Compared with the blank control, more autophagosomes were seen in HaCaT cells treated with matrine at 0.4 mg/mL by transmission electron microscopy (2.667 ± 1.202 vs. 21.33 ± 1.453, t = 9.899, P < 0.01). Cell proliferation inhibition and degree of the G0/G1 phase arrest was significantly higher in matrine plus acitretin group than those in matrine, acitretin, or the NS control group (P < 0.01, respectively). Compared with matrine or acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in matrine plus acitretin group increased significantly and the expression of cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with matrine or acitretin, matrine plus acitretin significantly down-regulated the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its downstream p-p70S6K (P < 0.05). In addition, the cumulative score of mice in the matrine plus acitretin group was significantly better than that in the matrine or acitretin group (1.480 ± 0.230 vs. 2.370 ± 0.241, P < 0.01;1.480 ± 0.230 vs. 2.888 ± 0.341, P < 0.01). The expression of LC3 protein in the matrine plus acitretin group was also higher than that in the matrine, acitretin, or the NS control group (P < 0.05, respectively). Conclusions: Matrine has therapeutic potentials for psoriasis. Matrine and acitretin show synergistic effect via cell cycle arrest and autophagy induction by PI3K/Akt/mTOR pathway.展开更多
We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patie...We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital (Shanghai, China) from May 2007 to November 2015. TSV was successfully performed in 381 cases (90.9%). Hemospermia was alleviated or disappeared in 324 (85.0%) patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 (1.9%), 32 (7.6%), 341 (81.4%), and 38 (9.1%) cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.展开更多
Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been sugg...Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer.However,the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups,and contradictory results have been reported in Asian patients.We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians.We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China.We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan–Meier analysis.Finally,a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients.McNemar’s test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods.The positive rates of TMPRSS2-ERG fusion were 16%in our samples and 27%in Asian patients.In our samples,9.4%and 19.3%of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry,respectively.No significant association between the fusion and clinical parameters was observed.TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China.Besides ethnic difference,detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.展开更多
Prostate cancer(PCa)risk calculators(RCs)with prostate-specific antigen(PSA)and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA.The European Randomized Study of ...Prostate cancer(PCa)risk calculators(RCs)with prostate-specific antigen(PSA)and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA.The European Randomized Study of Screening for PCa Risk Calculator(ERSPC-RC)and the Prostate Cancer Prevention Trial Risk Calculator(PCPT-RC)are developed on the Western population.However,the Western RCs showed limited diagnostic efficacy in the Eastern Asian population,mainly due to racial differences between the two populations.We aimed to review the application of Western RCs and Eastern Asian RCs in Eastern Asian cohorts and to identify the characteristics and efficacy of these RCs.展开更多
Psoriasis is a common chronic recurrent inflammatory disease.Plaque psoriasis accounts for more than 90%of psoriasis patients.Currently,no therapies are curative.Biologics have greatly improved the clinical efficacy a...Psoriasis is a common chronic recurrent inflammatory disease.Plaque psoriasis accounts for more than 90%of psoriasis patients.Currently,no therapies are curative.Biologics have greatly improved the clinical efficacy and potentially provide a better long-term safety profile,with respect to toxicity to major organs,than conventional treatments;however,relapse after treatment withdrawal is still an important issue.Although maintenance treatment is recommended in most guidelines,treatment withdrawal occurs quite frequently in real-world clinical practice.Thus,the time to relapse is an important consideration when choosing among the different therapies.展开更多
Magnetic skyrmion, which is a kind of swirl-like topological protected spin structure, shows great potential in the racetrack memory. So far, this progress is in obstacle by the skyrmion Hall effect which means that t...Magnetic skyrmion, which is a kind of swirl-like topological protected spin structure, shows great potential in the racetrack memory. So far, this progress is in obstacle by the skyrmion Hall effect which means that the direction of skyrmion motion will deviate from the driving direction.展开更多
A series of novel praseodymium(Pr)-bonded polymers were successfully synthesized via the coordination reaction and palladium-catalyzed Suzuki coupling reaction of 2,7-dibromo-9,9’-dioctylfluorene and different amou...A series of novel praseodymium(Pr)-bonded polymers were successfully synthesized via the coordination reaction and palladium-catalyzed Suzuki coupling reaction of 2,7-dibromo-9,9’-dioctylfluorene and different amounts of 5,5’-dibromo-2,2’-bipyridine. The resulting polymers were characterized by;H-NMR and GPC. The photoluminescence(PL) and electroluminescence(EL) properties of the resulting polymers were studied to explore the effects of the Pr triisopropyloxide. The results showed that the incorporation of Pr into the polymers caused better coplanarity and effective intermolecular or intramolecular interaction, leading to the higher emission intensity at long-wavelength. Further, it was also found that the emission light color could be tuned from blue to green by introduction of a small amount of Pr into the polymer main chain. A single-layer green emitting EL device based on PF(Bipy Pr)6 with 6 mol% Pr content was fabricated. The device had a low turn-on voltage of 6 V, a brightness of 705.3 cd·m;, the maximum luminous efficiency of 1.53 cd·A;and the maximum power efficiency of 0.69 lm·W;.展开更多
To the Editor:Generalized pustular psoriasis(GPP)is a rare and severe form of psoriasis for which traditional treatment approaches may not be effective.The traditional approach is systemic treatment with acitretin,met...To the Editor:Generalized pustular psoriasis(GPP)is a rare and severe form of psoriasis for which traditional treatment approaches may not be effective.The traditional approach is systemic treatment with acitretin,methotrexate,and cyclosporin;however,obvious side effects often occur during drug administration,limiting their clinical application.Secukinumab,a fully human anti-interleukin(IL)-17A monoclonal antibody,demonstrates efficacy in treating moderate to severe plaque-type psoriasis.Nonetheless,there are limited evidence-based real-world data on GPP treatment with secukinumab.Two cases of GPP were successfully treated with secukinumab in Peking University Third Hospital recently.This study was approved by the Ethics Committee of our hospital(No.328-01).展开更多
To the Editor:Psoriasis is a chronic,recurrent,systemic,immune-mediated inflammatory disease that mainly affects the skin,nails,and joints.Plaque psoriasis is the most common type of psoriasis,accounting for more than...To the Editor:Psoriasis is a chronic,recurrent,systemic,immune-mediated inflammatory disease that mainly affects the skin,nails,and joints.Plaque psoriasis is the most common type of psoriasis,accounting for more than 80%to 90%of all cases.Secukinumab,a human IgG monoclonal antibody that antagonizes interleukin 17A(IL-17A),was approved by the US Food and Drug Administration in 2015 to treat moderate-to-severe plaque psoriasis.A Chinese multicenter,double-blind,placebo-controlled phase III randomized clinical trial(RCT)demonstrated excellent efficacy and safety.[1]Secukinumab has been available on the Chinese market since May 2019,with a recommended dose of 300 mg.It is well-known that RCTs,due to their rigorous,normalized design schemes,cannot fully reflect what happens in clinical practice settings.The concept of the"efficacy-effectiveness gap"was also introduced,[2]which supports the importance of real-world study.Here,we retrospectively summarized all the inpatients with plaque psoriasis who were treated with secukinumab at Peking University Third Hospital from June to December 2019.General information(sex,age,weight,body mass index,etc.)and clinical features(disease duration,family history,comorbidities,laboratory tests,previous treatments,concomitant treatments,etc.)were collected from clinical records.The psoriasis area severity index(PASI),body surface area(BSA),dermatology life quality index(DLQI),psoriasis scalp severity index(PSSI),nail psoriasis severity index(NAPSI),and palmoplantar psoriasis area and severity index(ppPASI)were also recorded.展开更多
Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-...Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.展开更多
A new one-step synthesis of 3-hydroxymethylbenzofuran, based on intramolecular cyclization of 2- (methoxymethyl)-2-(2'-methoxymethyl-4'-methylphenyl)-butanone I under diluted hydrochloric acid in THF, was develo...A new one-step synthesis of 3-hydroxymethylbenzofuran, based on intramolecular cyclization of 2- (methoxymethyl)-2-(2'-methoxymethyl-4'-methylphenyl)-butanone I under diluted hydrochloric acid in THF, was developed. The mechanism for this process was investigated via chemical equilibrium shift of tautomer in acidic conditions. The applicability of this new method was studied further in this paper.展开更多
基金the National Nature Science Foundation of China(Nos.U2167204,11975040,and U1832130)the Brazilian funding agencies CAPES,CNPq,FAPERJ,and the INCT-FNA(Instituto Nacional de Ciência e Tecnologia-Física Nuclear e Aplicações)+5 种基金research project 464898/2014-5.S.P.Hu was supported by Guang dong Key Research And Development Program(No.2020B040420005)Guang dong Basic and Applied Basic Research Foundation(No.2021B1515120027)Ling Chuang Research Project of China National Nuclear Corporation(No.20221024000072F6-0002-7)Nuclear Energy Development and Research Project(No.HNKF202224(28))the‘111’center(B20065)the U.S.Department of Energy,Office of Science,Office of Nuclear Physics,under contract number DE-AC02-06CH1135.
文摘One-neutron stripping process between^(6)Li and^(209)Bi was studied at 28,30,and 34 MeV using the in-beamγ-ray spectroscopy method.Theγ-γcoincident analysis clearly identified twoγ-rays feeding the ground and long-lived isomeric states,which were employed to determine the cross section.The one-neutron stripping cross sections were similar to the cross sections of complete fusion in the^(6)Li+^(209)Bi system,but the one-neutron stripping cross sections decreased more gradually at the sub-barrier region.A coupled-reaction-channel calculation was performed to study the detailed reaction mechanism of the one-neutron stripping process in^(6)Li.The calculations indicated that the first excited state of 5 Li is critical in the actual one-neutron transfer mechanism,and the valence proton of 209Bi can be excited to the low-lying excited state in(^(6)Li,^(5)Li)reaction,unlike in the(d,p)reaction.
基金supported by the Project of the 940 Hospital of the Joint Logistics Support Force of the Chinese PLA(no.2021yxky057).
文摘Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.
基金supported by the National Natural Science Foundation of China,No.81 8 70985 (to FH)Project of Shandong Province Higher Education Science and Technology Program,No.J18KA258 (to NLZ)+1 种基金Xu Rongxiang Regenerative Medicine Science and Technology Program of Binzhou Medical University,No.BY2020XRX06 (to NLZ)the Natural Science Foundation of Shandong Province,No.BS2015SW021 (to NLZ)。
文摘Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection injury.We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually decreased.To investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord tissue.We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury.Qualitative observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co rd.Additionally,transmission electron microscopy showed that axon and myelin sheath morphology was restored.Silencing serum response factor had the opposite effects of ove rexpression.These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury.The underlying mechanism may be related to the regulation of axonal regeneration.
基金supported by the Wuxi Foundation for Development of Science and Technology of China,No.WX18IIAN041(to JHC)the Major Project of Nanjing Military Area Research Fund of China,No.15DX003(to JHC)the Wuxi Youth Medical Fund of China,No.QNRC046(to TW)
文摘Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna.Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage,12 and 36 hours after subarachnoid hemorrhage.Compared with the controls,atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage,neurological function had clearly improved;brain edema was remarkably relieved;cell apoptosis was markedly reduced in the cerebral cortex of rats;the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only.The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated.The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage.However,these were contrary to the results of 3-methyladenine injection,which inhibits the signaling pathway of autophagy.These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy.The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University,China(904 Hospital of Joint Logistic Support Force of PLA;approval No.YXLL-2017-09)on February 22,2017.
基金the National Natural Science Foundation of China(Grant No.51471059).
文摘A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles would settle down under the force of gravity.High volume fraction(50%)particle reinforced AZ91 composites could be easily obtained via this novel method.This is difficult to achieve for other traditional liquid fabrication methods.In addition,there was a good dispersion of TC4 particles in the AZ91 matrix and no clusters were found,which indicate that this method was feasible.Interfacial reaction occurred and the reaction product was confirmed to be Al2Ti.Three kinds of pre-dispersion technologies were used before the settling process and different interfacial microstructures were found.Theoretical calculation and experimental results both indicated that the interfacial product which was embedded in the matrix strengthened the composites and improved the tensile strength.
基金This work was supported by National Natural Science Foundation of China(11655003)Innovation Project of IHEP(542017IHEPZZBS11820)This work was supported in part by the CAS Center for Excellence in Particle Physics(CCEPP).
文摘Based on the LINAC of BEPCII, a high-polarized, high bightness, energy-tunable, monoenergetic laser compton backscattering (LCS)gamma-ray source is under construction at IHEP. The gamma-ray energy range is from 1 MeV to 111 MeV. It is a powerful and hopeful researchplatform to reveal the underlying physics of the nuclear, the basic particles and the vacuum or to check the exist basic physical models, quantumelectrodynamic (QED) theories. In the platform, a 1.064 mm Nd:YAG laser system and a 10.6 mm CO_(2) laser system are employed. All the triggersignals to the laser system and the electron control system are from the only reference clock at the very beginning of the LINAC to make sure thetemporal synchronization. Two optical transition radiation (OTR) targets and two charged-couple devices (CCD) are used to monitor and to alignthe electron beam and the laser beam. With the LCS gamma-ray source, it is proposed to experimentally check the gamma-ray calibrations, thephoton-nuclear physics, nuclear astrophysics and some basic QED phenomena.
文摘Given the challenges facing the cyberspace of the nation, this paper presents the tripartite theory of cyberspace, based on the status quo of cyberspace. Corresponding strategies and a research architecture are proposed for common public networks (C space), secure classified networks (S space), and key infras- tructure networks (K space), based on their individual characteristics. The features and security require- ments of these networks are then discussed. Taking C space as an example, we introduce the SMCRC (which stands for "situation awareness, monitoring and management, cooperative defense, response and recovery, and countermeasures and traceback") loop for constructing a cyberspace security ecosys- tem. Following a discussion on its characteristics and information exchange, our analysis focuses on the critical technologies of the SMCRC loop. To obtain more insight into national cyberspace security, special attention should be paid to global sensing and precise mapping, continuous detection and active manage- ment, cross-domain cooperation and systematic defense, autonomous response and rapid processing, and accurate traceback and countermeasure deterrence.
基金supported by the National Nature Science Foundation of China(No.11605009)China Scholarship Council,the U.S.Department of Energy under Grant No.DE-SC0014530+1 种基金the National Science Foundation(No.PHY-1565546)the Fundamental Research Funds for the Central Universities(No.2018NTST08)
文摘Finite element analysis(FEA) method was employed to perform three-dimensional(3D) electric field simulations for gas detectors with multiple wire electrodes.A new element refinement method developed for use in conjunction with the FEA program ANSYS allows successful meshing of the wires without physically inputting the wires in the chamber geometry. First, we demonstrate a model with only one wire, for which we calculate the potential distributions on the central plane and the end-cap region. The results are compared to the calculations obtained using GARFIELD, a two-dimensional program that uses the nearly exact boundary element method. Then we extend the method to same model, but with seven wires.Our results suggest that the new method can be applied easily to the 3D electric field calculations for complicated gas detectors with many wires and complicated geometry such as multiwire proportional chambers and time projection chambers.
基金funded by the National Natural Science Foundation of China(No.81972560)the Beijing Municipal Natural Science Foundation(No.7202231).
文摘Objective:The ongoing coronavirus disease 2019(COVID-19)epidemic has caused extensive damage worldwide.We explored whether the medical care conduct of patients with psoriasis has changed and whether the COVID-19 epidemic has placed more psychological pressure on these patients.Methods:A questionnaire survey was administered to patients with psoriasis in the Dermatology Department of Peking University Third Hospital in July 2022.Information about the patients’general demographics,psoriasis condition,mental state of anxiety(Generalized Anxiety Disorder-7[GAD-7]score),changes in medical care conduct,and Concerns about COVID-19-Related Risk Score for Psoriasis(CCRSP,a self-designed questionnaire)was collected.Univariate analysis with the Mann-Whitney U test for continuous variables was used in the estimation of statistical differences.Results:A total of 112 patients with psoriasis completed the survey.Purchasing medicine was the factor that added difficulty for most participants(32.1%).Fewer participants(26.8%)encountered medical registration difficulties than economic and transportation difficulties.Nearly three-quarters of participants(73.2%)reported at least one medical care conduct change resulting from the COVID-19 epidemic.A small proportion of participants(12.5%)thought that COVID-19 prevented them from seeking medical services for psoriasis.The top three items that caused the most concern were psoriasis aggravation resulting from drug reduction and withdrawal because of COVID-19(44.7%),psoriasis aggravation after infection with COVID-19(38.4%),and psoriasis-related side effects of the COVID-19 vaccine(35.7%).The GAD-7 score of patients with a high CCRSP(score of>10)was significantly higher than that of patients with a low CCRSP(score of≤10)(nonparametric test,P=0.047).Conclusion:COVID-19 poses challenges and places a mental burden on patients with psoriasis.Doctors should regulate the medical behavior of patients with psoriasis according to their specific COVID-19 situation and help patients ease their anxiety to maintain the stability of their psoriasis condition.
文摘Background: Acitretin and matrine have been used in the treatment of psoriasis in China. This study was designed to investigate the role and related mechanisms of matrine alone and in combination with acitretin in the treatment of psoriasis in vitro and in vivo. Methods: HaCaT cells were treated with matrine at different concentrations of 0 (blank control), 0.2, 0.4, 0.8, and 1.6 mg/mL for 24, 48, 72 h, respectively. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay was used to assess the growth and proliferation of HaCaT cells. Cell cycle and apoptosis were detected by flow cytometry. Expression of protein was detected by Western blotting. Autophagy was observed by transmission electron microscopy. Then HaCaT cells were assigned to normal saline (NS) control group, matrine (0.4 mg/mL) group, acitretin (10 μmol/L) group, and matrine plus acitretin group, and the above methods were repeated. In animal experiments, the cumulative score (erythema, scaling, thickening) as a measure of the severity of inflammation was used to measure the skin performance of mice after treated with matrine 50 mg/kg, acitretin 4.5 mg/kg or combination of the two drugs on the psoriasis-like mouse models, respectively. Pathological findings of the lesions were observed, and the protein expressions in the lesions were detected by immunohistochemistry. Results: Cell proliferation inhibition was seen in HaCaT cells with treatment of matrine in a dose- and time-dependent manner (P < 0.01, respectively). Cell cycle G0/G1 phase arrest was observed in a dose-dependent way (P < 0.01). The expression of p21 (P < 0.05), LC3II/I (P < 0.01), and Beclin 1 (P < 0.01) increased and the expression of cyclin D1 (P < 0.05) decreased with increasing doses of matrine. Compared with the blank control, more autophagosomes were seen in HaCaT cells treated with matrine at 0.4 mg/mL by transmission electron microscopy (2.667 ± 1.202 vs. 21.33 ± 1.453, t = 9.899, P < 0.01). Cell proliferation inhibition and degree of the G0/G1 phase arrest was significantly higher in matrine plus acitretin group than those in matrine, acitretin, or the NS control group (P < 0.01, respectively). Compared with matrine or acitretin group, the expression of p21 (P < 0.05, P < 0.05) and LC3II/I (P < 0.01, P < 0.05) in matrine plus acitretin group increased significantly and the expression of cyclin D1 (P < 0.01, P < 0.05) and p62 (P < 0.05, P < 0.05) was reduced significantly. Compared with matrine or acitretin, matrine plus acitretin significantly down-regulated the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway (P < 0.05) and its downstream p-p70S6K (P < 0.05). In addition, the cumulative score of mice in the matrine plus acitretin group was significantly better than that in the matrine or acitretin group (1.480 ± 0.230 vs. 2.370 ± 0.241, P < 0.01;1.480 ± 0.230 vs. 2.888 ± 0.341, P < 0.01). The expression of LC3 protein in the matrine plus acitretin group was also higher than that in the matrine, acitretin, or the NS control group (P < 0.05, respectively). Conclusions: Matrine has therapeutic potentials for psoriasis. Matrine and acitretin show synergistic effect via cell cycle arrest and autophagy induction by PI3K/Akt/mTOR pathway.
文摘We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital (Shanghai, China) from May 2007 to November 2015. TSV was successfully performed in 381 cases (90.9%). Hemospermia was alleviated or disappeared in 324 (85.0%) patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 (1.9%), 32 (7.6%), 341 (81.4%), and 38 (9.1%) cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.
基金This research was funded by the National Nature Science Foundation Youth Project(Grant No.81702514)the National Natural Science Foundation of China(Grant No.81430058)the Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning(Grant No.20184Y0130).
文摘Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog(TMPRSS2-ERG fusion)is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer.However,the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups,and contradictory results have been reported in Asian patients.We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians.We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China.We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan–Meier analysis.Finally,a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients.McNemar’s test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods.The positive rates of TMPRSS2-ERG fusion were 16%in our samples and 27%in Asian patients.In our samples,9.4%and 19.3%of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry,respectively.No significant association between the fusion and clinical parameters was observed.TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China.Besides ethnic difference,detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
基金This study is supported by the Fund for National Natural Science Foundation Youth Project(No.81702514 to RC).
文摘Prostate cancer(PCa)risk calculators(RCs)with prostate-specific antigen(PSA)and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA.The European Randomized Study of Screening for PCa Risk Calculator(ERSPC-RC)and the Prostate Cancer Prevention Trial Risk Calculator(PCPT-RC)are developed on the Western population.However,the Western RCs showed limited diagnostic efficacy in the Eastern Asian population,mainly due to racial differences between the two populations.We aimed to review the application of Western RCs and Eastern Asian RCs in Eastern Asian cohorts and to identify the characteristics and efficacy of these RCs.
基金the 2019 Grant of Milstein Medical Asian American Partnership Foundation.
文摘Psoriasis is a common chronic recurrent inflammatory disease.Plaque psoriasis accounts for more than 90%of psoriasis patients.Currently,no therapies are curative.Biologics have greatly improved the clinical efficacy and potentially provide a better long-term safety profile,with respect to toxicity to major organs,than conventional treatments;however,relapse after treatment withdrawal is still an important issue.Although maintenance treatment is recommended in most guidelines,treatment withdrawal occurs quite frequently in real-world clinical practice.Thus,the time to relapse is an important consideration when choosing among the different therapies.
基金financially supported by the National Natural Scientific Fund of China (Nos. 51771086 and 12074158)the Program of the Ministry of Education of China for Introducing Talents of Discipline to Universities (No. B20063)。
文摘Magnetic skyrmion, which is a kind of swirl-like topological protected spin structure, shows great potential in the racetrack memory. So far, this progress is in obstacle by the skyrmion Hall effect which means that the direction of skyrmion motion will deviate from the driving direction.
基金financially supported by the National Natural Science Foundation of China(Nos.21574021 and 51573026)the Natural Science Foundation of Fujian Province(No.2015J01189)+1 种基金the Program for Innovative Research Team in Science and Technology in Fujian Province(IRTSTFJ)the Program of the Education Department of Fujian Province(No.JA14078)
文摘A series of novel praseodymium(Pr)-bonded polymers were successfully synthesized via the coordination reaction and palladium-catalyzed Suzuki coupling reaction of 2,7-dibromo-9,9’-dioctylfluorene and different amounts of 5,5’-dibromo-2,2’-bipyridine. The resulting polymers were characterized by;H-NMR and GPC. The photoluminescence(PL) and electroluminescence(EL) properties of the resulting polymers were studied to explore the effects of the Pr triisopropyloxide. The results showed that the incorporation of Pr into the polymers caused better coplanarity and effective intermolecular or intramolecular interaction, leading to the higher emission intensity at long-wavelength. Further, it was also found that the emission light color could be tuned from blue to green by introduction of a small amount of Pr into the polymer main chain. A single-layer green emitting EL device based on PF(Bipy Pr)6 with 6 mol% Pr content was fabricated. The device had a low turn-on voltage of 6 V, a brightness of 705.3 cd·m;, the maximum luminous efficiency of 1.53 cd·A;and the maximum power efficiency of 0.69 lm·W;.
文摘To the Editor:Generalized pustular psoriasis(GPP)is a rare and severe form of psoriasis for which traditional treatment approaches may not be effective.The traditional approach is systemic treatment with acitretin,methotrexate,and cyclosporin;however,obvious side effects often occur during drug administration,limiting their clinical application.Secukinumab,a fully human anti-interleukin(IL)-17A monoclonal antibody,demonstrates efficacy in treating moderate to severe plaque-type psoriasis.Nonetheless,there are limited evidence-based real-world data on GPP treatment with secukinumab.Two cases of GPP were successfully treated with secukinumab in Peking University Third Hospital recently.This study was approved by the Ethics Committee of our hospital(No.328-01).
基金National Natural Science Foundation of China(No.81972560)Beijing Municipal Natural Science Foundation(No.7202231)。
文摘To the Editor:Psoriasis is a chronic,recurrent,systemic,immune-mediated inflammatory disease that mainly affects the skin,nails,and joints.Plaque psoriasis is the most common type of psoriasis,accounting for more than 80%to 90%of all cases.Secukinumab,a human IgG monoclonal antibody that antagonizes interleukin 17A(IL-17A),was approved by the US Food and Drug Administration in 2015 to treat moderate-to-severe plaque psoriasis.A Chinese multicenter,double-blind,placebo-controlled phase III randomized clinical trial(RCT)demonstrated excellent efficacy and safety.[1]Secukinumab has been available on the Chinese market since May 2019,with a recommended dose of 300 mg.It is well-known that RCTs,due to their rigorous,normalized design schemes,cannot fully reflect what happens in clinical practice settings.The concept of the"efficacy-effectiveness gap"was also introduced,[2]which supports the importance of real-world study.Here,we retrospectively summarized all the inpatients with plaque psoriasis who were treated with secukinumab at Peking University Third Hospital from June to December 2019.General information(sex,age,weight,body mass index,etc.)and clinical features(disease duration,family history,comorbidities,laboratory tests,previous treatments,concomitant treatments,etc.)were collected from clinical records.The psoriasis area severity index(PASI),body surface area(BSA),dermatology life quality index(DLQI),psoriasis scalp severity index(PSSI),nail psoriasis severity index(NAPSI),and palmoplantar psoriasis area and severity index(ppPASI)were also recorded.
基金The phase III trial on which this subanalysis is based (NCT03912259) was sponsored by Sanofi. Medical writing assistance with the preparation of this article was also funded by Sanofi.
文摘Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.
基金supported by the National Mega-Project for Innovative Drugs (No. 2012zx09301002-002)State Key Laboratory of Bioactive Substance and Function of Natural Medicines
文摘A new one-step synthesis of 3-hydroxymethylbenzofuran, based on intramolecular cyclization of 2- (methoxymethyl)-2-(2'-methoxymethyl-4'-methylphenyl)-butanone I under diluted hydrochloric acid in THF, was developed. The mechanism for this process was investigated via chemical equilibrium shift of tautomer in acidic conditions. The applicability of this new method was studied further in this paper.