The formation of wood is affected by the growing season and the environment.Ring-porous tree species have distinct earlywood-latewood differences.However,it is not clear how early wood and latewood respond to drought ...The formation of wood is affected by the growing season and the environment.Ring-porous tree species have distinct earlywood-latewood differences.However,it is not clear how early wood and latewood respond to drought and the differences in adaptation.Therefore,based on the analyses of phenology,growth,and xylem development over a year,xylem development in Fraxinus mandshurica was divided into earlyw ood,transition,and latewood stages.Variation patterns of 38 wood indices from 31 genotypes indicated that the formation of wood tissues was inhibited,and the proportion of xylem cells was affected by drought at each stage.However,soluble sugar affected osmotic regulation only during drought across early wood and transition stages.To maintain water and nutrient transport during drought and to resist embolism risk,drought in the early wood stage leads to varying degrees of early wood vessel diameter reduction,with pits enlarging to compensate.In contrast,during the late wood stage,drought causes latewood vessel diameter to increase and pits to shrink accordingly.In addition,the results indicate that several wood indices correlate with drought resistance at each stage,but early wood vessel diameter,soluble sugar,and latewood ves sel diameters exhibited the strongest correlations in the early wood,transition,and latewood stages.These findings provide clues to understanding plant survival strategies under drought stress and are of significance for plant ecology research on the growth and adaptation of tree species under climate change.展开更多
Cerium fluoride(CeF_(3))semiconductor with upconversion property was constructed on graphite carbonitride(g-C_(3) N_(4))nanosheets by microwave hydrothermal method.The X-ray diffraction,transmission election microscop...Cerium fluoride(CeF_(3))semiconductor with upconversion property was constructed on graphite carbonitride(g-C_(3) N_(4))nanosheets by microwave hydrothermal method.The X-ray diffraction,transmission election microscopy,Fourier transform infrared,and X-ray photoelectron spectra techniques were used to characterize the CeF_(3)/g-C_(3)N_(4) nanocomposite.The study shows that CeF_(3) has upconversion property and can convert visible light(Vis)and near-infrared light(NIR)into ultraviolet light(UV).Mo reover,CeF3 and g-C_(3) N_(4) can form well-defined heterojunction and promote the effective separation of photogenerated electrons and holes.The synergistic effect of the CeF_(3)/g-C_(3)N_(4) nanocomposite was evaluated by photocatalytic degradation of dibenzothiophene(DBT).The optimum photocatalyst of CeF_(3)/g-C_(3)N_(4)(40 wt%)composites exhibit the highest photocatalytic desulfurization rate of the model oil under visible light radiation.展开更多
Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethra...Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.展开更多
BACKGROUND Urothelial encrusted pyelo-ureteritis disease is an infrequent condition and there is no unified surgical treatment and reference standard to consult.We have used a minimally invasive endoscopic method to t...BACKGROUND Urothelial encrusted pyelo-ureteritis disease is an infrequent condition and there is no unified surgical treatment and reference standard to consult.We have used a minimally invasive endoscopic method to treat three such cases,which yielded excellent results.CASE SUMMARY The first case was a 45-year-old man who had unilateral ureteropelvic junction(UPJ)atresia and contralateral stenosis and was treated by double endoscopic surgery using an anterograde percutaneous nephroscope coupled with a rigid retrograde ureteroscope.The second case was a 12-year-old boy who received a percutaneous nephroscopy on one side and a percutaneous nephroscopy with a rigid ureteroscope on the other side due to the presence of bilateral UPJ stenosis.The third case was a 32-year-old woman with bilateral lower ureteral stricture treated using a rigid retrograde ureteroscope.Endoscopic surgeries were successfully performed on all the three patients.Varying degrees of encrustation and erosion of the urothelium were observed during the operation.The calcified layer composition analysis showed magnesium ammonium phosphate or carbonate apatite.Two patients achieved a good prognosis.CONCLUSION Minimally invasive endoscopic treatment for urothelial encrusted pyelo-ureteritis disease can yield better results.展开更多
Parallel computing assigns the computing model to different processors on different devices and implements it simultaneously.Accordingly,it has broad applications in the numerical simulation of geotechnical engineerin...Parallel computing assigns the computing model to different processors on different devices and implements it simultaneously.Accordingly,it has broad applications in the numerical simulation of geotechnical engineering and underground engineering,of which models are always large-scale.With parallel computing,the computing time or the memory requirements will be reduced by splitting the original domain of the numerical model into many subdomains,which is thus named as the domain decomposition method.In this study,a cubic and equal volume domain decomposition strategy was utilized to realize the parallel computing on the distributed memory system of four-dimensional lattice spring model(4D-LSM)based on the message passing interface.With a more efficient communication strategy introduced,this study aimed at operating an one-billion-particle model on a supercomputer platform.The preprocessing procedure of the parallelized 4D-LSM was restructured and the particle generation strategy suitable for the supercomputer platform was employed to minimize the time consumption in preprocessing and calculation.On this basis,numerical calculations were performed on TianHe-3 prototype E class supercomputer at the National Supercomputer Center in Tianjin.Two fieldscale three-dimensional blasting wave propagation models were carried out,of which the numerical results verify the computing power and the advantage of the parallelized 4D-LSM in the simulation of large-scale three-dimension models.Subsequently,the time complexity and spatial complexity of 4D-LSM and other particle discrete element methods were analyzed.展开更多
Ischemic cardiovascular diseases(ICVD),including ischemic stroke and coronary heart disease,has become the top cause of death in China[11.A 10-year 1CVD risk prediction model in Chinese adults has been developed and v...Ischemic cardiovascular diseases(ICVD),including ischemic stroke and coronary heart disease,has become the top cause of death in China[11.A 10-year 1CVD risk prediction model in Chinese adults has been developed and validated,which involved seven parameters including sex,age,systolic blood pressure,total cholesterol,body mass index,current smoking status,and diabetes[2].Since this model requires information from questionnaire,invasive blood tests,and physical examinations,its practice in primary healthcare settings is limited[2].展开更多
Concrete strength mainly depends on the hydration between water and cement and how the resulting calcium silicate hydrate(C-S-H)crystals binds the other concrete components together.Traditional empirical formulas can ...Concrete strength mainly depends on the hydration between water and cement and how the resulting calcium silicate hydrate(C-S-H)crystals binds the other concrete components together.Traditional empirical formulas can hardly incorporate all relevant factors to accurately predict concrete properties.Over the past two decades,newly developed machine learning algorithms have been applied to practical problems across different fields.These machine learning algorithms offer an alternative approach to predicting concrete properties(e.g.,strength and permeability),reconstruct digital twin models,and capture surface defects.This paper reviews the application and improvement of machine learning algorithms in predicting and characterizing the mechanical properties and morphology of concrete,including the traditional machine learning(K-nearest neighbors,support vector machines),artificial neural networks,deep learning models(convolutional neural networks and generative adversarial networks),and physics-informed neural networks.Potential models for the prediction or characterization of a specific property are summarized.This paper will help researchers in the area of concrete materials in selecting and establishing a machine learning model.展开更多
Percutaneous nephrolithotomy(PCNL)has achieved remarkable acceptance during the past decade.The minimization of the instruments used and flexible scope improvements helped lead to its popularity.A previous literature ...Percutaneous nephrolithotomy(PCNL)has achieved remarkable acceptance during the past decade.The minimization of the instruments used and flexible scope improvements helped lead to its popularity.A previous literature proved that the tract size was positively correlated with the rate of bleeding and renal injuries.11 On the basis of this conception,we devised a new PCNL technique,called"needle-perc"as the needle was even thinner than the micro-perc technique.In this study,we present our initial experience of using the needle-perc method to deal with small renal stones and to assess its feasibility and safety as new instrumentation in the field of minimally invasive endourology.展开更多
Background:Psoriasis is a common chronic inflammatory skin disease with 2%to 3%prevalence worldwide and a heavy social-psychological burden for patients and their families.As the exact pathogenesis of psoriasis is sti...Background:Psoriasis is a common chronic inflammatory skin disease with 2%to 3%prevalence worldwide and a heavy social-psychological burden for patients and their families.As the exact pathogenesis of psoriasis is still unknown,the current treatment is far from satisfactory.Thus,there is an urgent need to find a more effective therapy for this disease.Keratin 17(K17),a type I intermediate filament,is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis.Therefore,we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis.This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA(siRNA)on mice with imiquimod(IMQ)-induced psoriasis-like dermatitis.Methods:Eight-week-old female BALB/c mice were administered a 5%IMQ cream on both ears to produce psoriatic dermatitis.On day 3,K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days.The right ears of the mice were treated in parallel with negative control(NC)siRNA.Inflammation was evaluated by gross ear thickness,histopathology,the infiltration of inflammatory cells(CD3+T cells and neutrophils)using immunofluorescence,and the expression of cytokine production using real-time quantitative polymerase chain reaction.The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.Results:The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears,as evidenced by the alleviated ear inflammation phenotype,including decreased ear thickness,infiltration of inflammatory cells(CD3+T cells and neutrophils),and inflammatory cytokine/chemokine expression levels(interleukin 17[IL-17],IL-22,IL-23,C-X-C motif chemokine ligand 1,and C-C motif chemokine ligand 20)(P<0.05 vs.the Blank or NC siRNA groups).Compared to the NC siRNA treatment,the K17 siRNA treatment resulted in increased K1 and K10 expression,which are characteristic of keratinocyte differentiation(vs.NC siRNA,K17 siRNA1 group:K1,t=4.782,P=0.0050;K10,t=3.365,P=0.0120;K17 siRNA2 group:K1,t=4.104,P=0.0093;K10,t=4.168,P=0.0042;siRNA Mix group:K1,t=3.065,P=0.0221;K10,t=10.83,P<0.0001),and decreased K16 expression,which is characteristic of keratinocyte proliferation(vs.NC siRNA,K17 siRNA1 group:t=4.156,P=0.0043;K17 siRNA2 group:t=2.834,P=0.0253;siRNA Mix group:t=2.734,P=0.0250).Conclusions:Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis.Thus,gene therapy targeting K17 may be a potential treatment approach for psoriasis.展开更多
Introduction Psoriasis is a chronic,recurrent skin disease featured by scaly papules or plaques.Although the vast majority of patients have mild psoriasis,approxi-mately 20%-30% of patients have moderate or severe p...Introduction Psoriasis is a chronic,recurrent skin disease featured by scaly papules or plaques.Although the vast majority of patients have mild psoriasis,approxi-mately 20%-30% of patients have moderate or severe psoriasis,which is defined as body surface area (BSA) > 10,psoriasis area and severity index (PASI) > 10,and dermatology life quality index (DLQI) > 10.These patients have severe symptoms and worse quality of life,warranting consideration of systemic therapy[1].Biologic treatments directly target specific steps in the pathogenesis of psoriasis,providing a revolution for treatment.展开更多
基金supported by the National Key R&D Program of China(2021YFD2200303)the National Natural Science Foundation of China(32271903,U24A20428)。
文摘The formation of wood is affected by the growing season and the environment.Ring-porous tree species have distinct earlywood-latewood differences.However,it is not clear how early wood and latewood respond to drought and the differences in adaptation.Therefore,based on the analyses of phenology,growth,and xylem development over a year,xylem development in Fraxinus mandshurica was divided into earlyw ood,transition,and latewood stages.Variation patterns of 38 wood indices from 31 genotypes indicated that the formation of wood tissues was inhibited,and the proportion of xylem cells was affected by drought at each stage.However,soluble sugar affected osmotic regulation only during drought across early wood and transition stages.To maintain water and nutrient transport during drought and to resist embolism risk,drought in the early wood stage leads to varying degrees of early wood vessel diameter reduction,with pits enlarging to compensate.In contrast,during the late wood stage,drought causes latewood vessel diameter to increase and pits to shrink accordingly.In addition,the results indicate that several wood indices correlate with drought resistance at each stage,but early wood vessel diameter,soluble sugar,and latewood ves sel diameters exhibited the strongest correlations in the early wood,transition,and latewood stages.These findings provide clues to understanding plant survival strategies under drought stress and are of significance for plant ecology research on the growth and adaptation of tree species under climate change.
基金supported by the National Natural Science Foundation of China(11774178,51801172)the Jiangsu Province Key Laboratory of Materials Surface Science and Technology and School-level Research Projects of Yancheng Institute of Technology(xjr2019026)。
文摘Cerium fluoride(CeF_(3))semiconductor with upconversion property was constructed on graphite carbonitride(g-C_(3) N_(4))nanosheets by microwave hydrothermal method.The X-ray diffraction,transmission election microscopy,Fourier transform infrared,and X-ray photoelectron spectra techniques were used to characterize the CeF_(3)/g-C_(3)N_(4) nanocomposite.The study shows that CeF_(3) has upconversion property and can convert visible light(Vis)and near-infrared light(NIR)into ultraviolet light(UV).Mo reover,CeF3 and g-C_(3) N_(4) can form well-defined heterojunction and promote the effective separation of photogenerated electrons and holes.The synergistic effect of the CeF_(3)/g-C_(3)N_(4) nanocomposite was evaluated by photocatalytic degradation of dibenzothiophene(DBT).The optimum photocatalyst of CeF_(3)/g-C_(3)N_(4)(40 wt%)composites exhibit the highest photocatalytic desulfurization rate of the model oil under visible light radiation.
基金the National Key Research and Development Plan of China(Technology helps Economy 20202016YFC0106300)+1 种基金the National Natural Science Foundation of China(82174230)Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52).
文摘Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline “2018 Standard Edition”. However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy;the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.
文摘BACKGROUND Urothelial encrusted pyelo-ureteritis disease is an infrequent condition and there is no unified surgical treatment and reference standard to consult.We have used a minimally invasive endoscopic method to treat three such cases,which yielded excellent results.CASE SUMMARY The first case was a 45-year-old man who had unilateral ureteropelvic junction(UPJ)atresia and contralateral stenosis and was treated by double endoscopic surgery using an anterograde percutaneous nephroscope coupled with a rigid retrograde ureteroscope.The second case was a 12-year-old boy who received a percutaneous nephroscopy on one side and a percutaneous nephroscopy with a rigid ureteroscope on the other side due to the presence of bilateral UPJ stenosis.The third case was a 32-year-old woman with bilateral lower ureteral stricture treated using a rigid retrograde ureteroscope.Endoscopic surgeries were successfully performed on all the three patients.Varying degrees of encrustation and erosion of the urothelium were observed during the operation.The calcified layer composition analysis showed magnesium ammonium phosphate or carbonate apatite.Two patients achieved a good prognosis.CONCLUSION Minimally invasive endoscopic treatment for urothelial encrusted pyelo-ureteritis disease can yield better results.
基金National Natural Science Foundation of China,Grant/Award Number:51979187。
文摘Parallel computing assigns the computing model to different processors on different devices and implements it simultaneously.Accordingly,it has broad applications in the numerical simulation of geotechnical engineering and underground engineering,of which models are always large-scale.With parallel computing,the computing time or the memory requirements will be reduced by splitting the original domain of the numerical model into many subdomains,which is thus named as the domain decomposition method.In this study,a cubic and equal volume domain decomposition strategy was utilized to realize the parallel computing on the distributed memory system of four-dimensional lattice spring model(4D-LSM)based on the message passing interface.With a more efficient communication strategy introduced,this study aimed at operating an one-billion-particle model on a supercomputer platform.The preprocessing procedure of the parallelized 4D-LSM was restructured and the particle generation strategy suitable for the supercomputer platform was employed to minimize the time consumption in preprocessing and calculation.On this basis,numerical calculations were performed on TianHe-3 prototype E class supercomputer at the National Supercomputer Center in Tianjin.Two fieldscale three-dimensional blasting wave propagation models were carried out,of which the numerical results verify the computing power and the advantage of the parallelized 4D-LSM in the simulation of large-scale three-dimension models.Subsequently,the time complexity and spatial complexity of 4D-LSM and other particle discrete element methods were analyzed.
基金supported by the National Natural Science Foundation of China(81974489 and 81974490)。
文摘Ischemic cardiovascular diseases(ICVD),including ischemic stroke and coronary heart disease,has become the top cause of death in China[11.A 10-year 1CVD risk prediction model in Chinese adults has been developed and validated,which involved seven parameters including sex,age,systolic blood pressure,total cholesterol,body mass index,current smoking status,and diabetes[2].Since this model requires information from questionnaire,invasive blood tests,and physical examinations,its practice in primary healthcare settings is limited[2].
基金supported by the Central University Basic Research Fund of China(grant No.3072024CFJ0202).
文摘Concrete strength mainly depends on the hydration between water and cement and how the resulting calcium silicate hydrate(C-S-H)crystals binds the other concrete components together.Traditional empirical formulas can hardly incorporate all relevant factors to accurately predict concrete properties.Over the past two decades,newly developed machine learning algorithms have been applied to practical problems across different fields.These machine learning algorithms offer an alternative approach to predicting concrete properties(e.g.,strength and permeability),reconstruct digital twin models,and capture surface defects.This paper reviews the application and improvement of machine learning algorithms in predicting and characterizing the mechanical properties and morphology of concrete,including the traditional machine learning(K-nearest neighbors,support vector machines),artificial neural networks,deep learning models(convolutional neural networks and generative adversarial networks),and physics-informed neural networks.Potential models for the prediction or characterization of a specific property are summarized.This paper will help researchers in the area of concrete materials in selecting and establishing a machine learning model.
基金This study was supported by a grant of the Capital Health Research and Development of Special(No.2016-1-2241).
文摘Percutaneous nephrolithotomy(PCNL)has achieved remarkable acceptance during the past decade.The minimization of the instruments used and flexible scope improvements helped lead to its popularity.A previous literature proved that the tract size was positively correlated with the rate of bleeding and renal injuries.11 On the basis of this conception,we devised a new PCNL technique,called"needle-perc"as the needle was even thinner than the micro-perc technique.In this study,we present our initial experience of using the needle-perc method to deal with small renal stones and to assess its feasibility and safety as new instrumentation in the field of minimally invasive endourology.
基金National Natural Science Foundation of China(Nos.81803125 and 81903192)。
文摘Background:Psoriasis is a common chronic inflammatory skin disease with 2%to 3%prevalence worldwide and a heavy social-psychological burden for patients and their families.As the exact pathogenesis of psoriasis is still unknown,the current treatment is far from satisfactory.Thus,there is an urgent need to find a more effective therapy for this disease.Keratin 17(K17),a type I intermediate filament,is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis.Therefore,we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis.This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA(siRNA)on mice with imiquimod(IMQ)-induced psoriasis-like dermatitis.Methods:Eight-week-old female BALB/c mice were administered a 5%IMQ cream on both ears to produce psoriatic dermatitis.On day 3,K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days.The right ears of the mice were treated in parallel with negative control(NC)siRNA.Inflammation was evaluated by gross ear thickness,histopathology,the infiltration of inflammatory cells(CD3+T cells and neutrophils)using immunofluorescence,and the expression of cytokine production using real-time quantitative polymerase chain reaction.The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.Results:The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears,as evidenced by the alleviated ear inflammation phenotype,including decreased ear thickness,infiltration of inflammatory cells(CD3+T cells and neutrophils),and inflammatory cytokine/chemokine expression levels(interleukin 17[IL-17],IL-22,IL-23,C-X-C motif chemokine ligand 1,and C-C motif chemokine ligand 20)(P<0.05 vs.the Blank or NC siRNA groups).Compared to the NC siRNA treatment,the K17 siRNA treatment resulted in increased K1 and K10 expression,which are characteristic of keratinocyte differentiation(vs.NC siRNA,K17 siRNA1 group:K1,t=4.782,P=0.0050;K10,t=3.365,P=0.0120;K17 siRNA2 group:K1,t=4.104,P=0.0093;K10,t=4.168,P=0.0042;siRNA Mix group:K1,t=3.065,P=0.0221;K10,t=10.83,P<0.0001),and decreased K16 expression,which is characteristic of keratinocyte proliferation(vs.NC siRNA,K17 siRNA1 group:t=4.156,P=0.0043;K17 siRNA2 group:t=2.834,P=0.0253;siRNA Mix group:t=2.734,P=0.0250).Conclusions:Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis.Thus,gene therapy targeting K17 may be a potential treatment approach for psoriasis.
基金the Key Program of the National Natural Science Foundation of China(81430073)%General Program of the National Science Foundation of China(81371738)
文摘Introduction Psoriasis is a chronic,recurrent skin disease featured by scaly papules or plaques.Although the vast majority of patients have mild psoriasis,approxi-mately 20%-30% of patients have moderate or severe psoriasis,which is defined as body surface area (BSA) > 10,psoriasis area and severity index (PASI) > 10,and dermatology life quality index (DLQI) > 10.These patients have severe symptoms and worse quality of life,warranting consideration of systemic therapy[1].Biologic treatments directly target specific steps in the pathogenesis of psoriasis,providing a revolution for treatment.