BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective man...BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.展开更多
Robotic splicing of steel arches is a challenging task that is necessary to realize the grasping and docking of steel arches in a limited space.Steel arches often have a mass of more than 200 kg and length of more tha...Robotic splicing of steel arches is a challenging task that is necessary to realize the grasping and docking of steel arches in a limited space.Steel arches often have a mass of more than 200 kg and length of more than 4 m.Owing to the large volume and mass of steel arches and the high requirements for accurately positioning the splicing,it is difficult for a general manipulator to meet the stiffness requirements.To enhance the structural stiffness of the steel arch splicing manipulator,a single-degree-of-freedom(DOF)closed-loop mechanism was added to the grasping structure of the manipulator.Based on the basic principle of structural synthesis,a solution model of the single-DOF closed-loop mechanism was developed,and alternative kinematic pairs of the mechanism with different input constraints and output requirements were derived.Based on this model,a design method for a single-DOF closed-loop grasping mechanism and a posture adjustment mechanism for a steel arch was devised.Combined with the same dimensional subspace equivalence principle of the graphical-type synthesis method,12 types of steel arch splicing manipulator were constructed.By analyzing the motion/force transmission and structural complexity of the steel arch splicing manipulators,the best scheme was selected.A prototype of the steel arch splicing manipulator was manufactured.Adams software was used to obtain clearly the output trajectory of the end of the manipulator.The relative spatial positions of the upper and lower jaws under different working stages were analyzed,demonstrating that the manipulator satisfied the grasping requirements.Through a steel arch splicing experiment,the grasping effect,docking accuracy,and splicing efficiency of the manipulator met the design requirements.The steel arch splicing manipulator can replace the manual completion of the steel arch splicing operation,significantly improving the operation efficiency.展开更多
Objective： To identify the miRNA specific signature as novel diagnostic and prognostic tools for gastric cancer. Methods： miRNAs expression profiling of 3 normal gastric tissues, 24 malignant tissues, gastric cance...Objective： To identify the miRNA specific signature as novel diagnostic and prognostic tools for gastric cancer. Methods： miRNAs expression profiling of 3 normal gastric tissues, 24 malignant tissues, gastric cancer cell SGC7901 and normal gastric cell GES-1 were detected using microarray technology. The hierarchical clustering algorithm of the Cluster software was used to analyse the miRNAs expression of all samples. The expression levels of miR-433 and miR-9 which were significantly down-regulated in gastric cancer tissues and SGC7901 cells by microarray technology were validated by quantitative Real-time PCR （qRT-PCR）. Results： Differential expressions of 26 individual miRNAs between normal samples （including 3 normal gastric tissues and GES-1 cells） and carcinomas （including 24 malignant tissues and SGC7901 cells） were discovered, 19 of them showing down-regulation and 7 up-regulation in carcinoma samples. Hierarchical clustering of the Cancer samples by their miRNA expression accurately separated the carcinomas from normal samples and further their histotypes of carcinomas. The expression levels of miR-433 and miR-9 were significantly down-regulated in gastric cancer tissues and SGC7901cells Conclusion： The differential expression of miR-433 and miR-9 may be used as a novel diagnostic tool for gastric cancer.展开更多
Heat stroke is the most severe type of heat illness,it is often accompanied by severe multiorgan damage and has a high fatality rate.In January 2020,based on new research evidence and the experiences of Chinese expert...Heat stroke is the most severe type of heat illness,it is often accompanied by severe multiorgan damage and has a high fatality rate.In January 2020,based on new research evidence and the experiences of Chinese experts in heat stroke,the Expert Group of Heat Stroke Prevention and Treatment of the Chinese People’s Liberation Army(PLA)and the Professional Committee of Critical Care Medicine of the Chinese PLA jointly issued a new Expert Consensus on the Diagnosis and Treatment of Heat Stroke in China.This article aims to interpret and supplement the major updates to the new consensus.展开更多
Developing effective and practical electrocatalyst under industrial electrolysis conditions is critical for renewable hydrogen production.Herein,we report the self-supporting NiFe LDH-MoS_(x) integrated electrode for ...Developing effective and practical electrocatalyst under industrial electrolysis conditions is critical for renewable hydrogen production.Herein,we report the self-supporting NiFe LDH-MoS_(x) integrated electrode for water oxidation under normal alkaline test condition(1 M KOH at 25℃)and simulated industrial electrolysis conditions(5 M KOH at 65℃).Such optimized electrode exhibits excellent oxygen evolution reaction(OER)performance with overpotential of 195 and 290 mV at current density of 100 and 400 mA·cm^(-2) under normal alkaline test condition.Notably,only over-potential of 156 and 201 mV were required to achieve the current density of 100 and 400mA·cm^(-2) under simulated industrial electrolysis conditions.No significant degradations were observed after long-term durability tests for both conditions.When using in two-electrode system,the operational voltages of 1.44 and 1.72 V were required to achieve a current density of 10 and 100 mA·cm^(-2) for the overall water splitting test(NiFe LDH-MoS_(x)/INF||20%Pt/C).Additionally,the operational voltage of employing NiFe LDH-MoS_(x)/INF as both cathode and anode merely require 1.52 V at 50mA·cm^(-2) at simulated industrial electrolysis conditions.Notably,a membrane electrode assembly(MEA)for anion exchange membrane water electrolysis(AEMWEs)using NiFe LDH-MoS_(x)/INF as an anode catalyst exhibited an energy conversion efficiency of 71.8%at current density of 400 mA·cm^(-2)in 1 M KOH at 60℃.Further experimental results reveal that sulfurized substrate not only improved the conductivity of NiFe LDH,but also regulated its electronic configurations and atomic composition,leading to the excellent activity.The easy-obtained and cost-effective integrated electrodes are expected to meet the large-scale application of industrial water electrolysis.展开更多
Composite membranes and sponge scaffolds consisting chitosan (CS) and acellular derm matrix (ADM) in six ratios were prepared by solvent evaporation technique and freeze-drying method, respectively. The composite mate...Composite membranes and sponge scaffolds consisting chitosan (CS) and acellular derm matrix (ADM) in six ratios were prepared by solvent evaporation technique and freeze-drying method, respectively. The composite materials were characterized by water contact angle measurement, scanning electron microscopy (SEM), water absorption and HaCat cells compatibility. The SEM result showed that CS/ADM three-dimensional (3D) micro-porous structures were successfully produced. The water absorption value of all scaffolds was over 18 times of its initial weight, which is high enough for skin regeneration scaffold, but there were no significant differences of water absorption ratio between deionized water and PBS solution for same scaffold (P > 0.05). HaCat cells were distributed uniformly on the surfaces of membrane 4-6, and an almost confluent monolayer was formed on membrane 6 on the fifth day, whereas cells maintained round and spherical in shape on the surface of membrane 1. The results showed that the cell compatibility of pure CS membrane needed to be improved, and addition of ADM realized this purpose. The results of compatibility of HaCat cells on scaffolds showed that the cell proliferated well on the scaffolds 3 and 4. In our study, the cell’s attachment and growth on the composite membranes was mainly determined by the content of the membrane, whereas the cell’s attachment and growth in the scaffolds was determined by both the content and structure of the scaffolds.展开更多
1 Introduction The k-NN(k Nearest Neighbors)searching problem on road network constitutes a crucial aspect of location-oriented services,which has boasted the practical implications.
Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China...Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.展开更多
The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here,...The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 （PHF20） functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout （KO） for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly（ADP-ribose） polymerase 1 （PARP1） and directly binds to promoter regions of octamer-binding transcription factor 4 （OCT4） and sex determining region Y-box 2 （SOX2） to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit （H3K4me3）. Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.展开更多
1 Introduction With the rapid development of mobile networks,locationbased services has become popular in the daily lives of people.The service providers can recommend the profitable services to persons through mining...1 Introduction With the rapid development of mobile networks,locationbased services has become popular in the daily lives of people.The service providers can recommend the profitable services to persons through mining the frequent interests or places of persons.However,one aspect is that the historical data on Internet can easily cause the leakage of user-relationship privacy,another aspect is that the historical interests of person are always bound to time.Therefore,this paper devotes to study a privacy protection method on time-constrained point of interests(PoIs)based on the group relationships of users.展开更多
Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient ce...Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.展开更多
文摘BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.
基金Supported by Special funding support for the construction of innovative provinces in Hunan Province(Grant No.2019GK1010)National Key R&D Program of China(Grant No.2017YFB1302600).
文摘Robotic splicing of steel arches is a challenging task that is necessary to realize the grasping and docking of steel arches in a limited space.Steel arches often have a mass of more than 200 kg and length of more than 4 m.Owing to the large volume and mass of steel arches and the high requirements for accurately positioning the splicing,it is difficult for a general manipulator to meet the stiffness requirements.To enhance the structural stiffness of the steel arch splicing manipulator,a single-degree-of-freedom(DOF)closed-loop mechanism was added to the grasping structure of the manipulator.Based on the basic principle of structural synthesis,a solution model of the single-DOF closed-loop mechanism was developed,and alternative kinematic pairs of the mechanism with different input constraints and output requirements were derived.Based on this model,a design method for a single-DOF closed-loop grasping mechanism and a posture adjustment mechanism for a steel arch was devised.Combined with the same dimensional subspace equivalence principle of the graphical-type synthesis method,12 types of steel arch splicing manipulator were constructed.By analyzing the motion/force transmission and structural complexity of the steel arch splicing manipulators,the best scheme was selected.A prototype of the steel arch splicing manipulator was manufactured.Adams software was used to obtain clearly the output trajectory of the end of the manipulator.The relative spatial positions of the upper and lower jaws under different working stages were analyzed,demonstrating that the manipulator satisfied the grasping requirements.Through a steel arch splicing experiment,the grasping effect,docking accuracy,and splicing efficiency of the manipulator met the design requirements.The steel arch splicing manipulator can replace the manual completion of the steel arch splicing operation,significantly improving the operation efficiency.
基金supported by a grant from Chongqing City Board of Education, China (No.KJ060302).
文摘Objective： To identify the miRNA specific signature as novel diagnostic and prognostic tools for gastric cancer. Methods： miRNAs expression profiling of 3 normal gastric tissues, 24 malignant tissues, gastric cancer cell SGC7901 and normal gastric cell GES-1 were detected using microarray technology. The hierarchical clustering algorithm of the Cluster software was used to analyse the miRNAs expression of all samples. The expression levels of miR-433 and miR-9 which were significantly down-regulated in gastric cancer tissues and SGC7901 cells by microarray technology were validated by quantitative Real-time PCR （qRT-PCR）. Results： Differential expressions of 26 individual miRNAs between normal samples （including 3 normal gastric tissues and GES-1 cells） and carcinomas （including 24 malignant tissues and SGC7901 cells） were discovered, 19 of them showing down-regulation and 7 up-regulation in carcinoma samples. Hierarchical clustering of the Cancer samples by their miRNA expression accurately separated the carcinomas from normal samples and further their histotypes of carcinomas. The expression levels of miR-433 and miR-9 were significantly down-regulated in gastric cancer tissues and SGC7901cells Conclusion： The differential expression of miR-433 and miR-9 may be used as a novel diagnostic tool for gastric cancer.
基金supported by the Military Medical Innovation Project Fund(18CXZ01918CXZ024)+2 种基金a Chinese military fund dedicated tosupported by the Military Medical Innovation Project Fund(18CXZ01918CXZ024)a Chinese military fund dedicated to the prevention and control of heat-related illness with no commercial interest。
文摘Heat stroke is the most severe type of heat illness,it is often accompanied by severe multiorgan damage and has a high fatality rate.In January 2020,based on new research evidence and the experiences of Chinese experts in heat stroke,the Expert Group of Heat Stroke Prevention and Treatment of the Chinese People’s Liberation Army(PLA)and the Professional Committee of Critical Care Medicine of the Chinese PLA jointly issued a new Expert Consensus on the Diagnosis and Treatment of Heat Stroke in China.This article aims to interpret and supplement the major updates to the new consensus.
文摘Developing effective and practical electrocatalyst under industrial electrolysis conditions is critical for renewable hydrogen production.Herein,we report the self-supporting NiFe LDH-MoS_(x) integrated electrode for water oxidation under normal alkaline test condition(1 M KOH at 25℃)and simulated industrial electrolysis conditions(5 M KOH at 65℃).Such optimized electrode exhibits excellent oxygen evolution reaction(OER)performance with overpotential of 195 and 290 mV at current density of 100 and 400 mA·cm^(-2) under normal alkaline test condition.Notably,only over-potential of 156 and 201 mV were required to achieve the current density of 100 and 400mA·cm^(-2) under simulated industrial electrolysis conditions.No significant degradations were observed after long-term durability tests for both conditions.When using in two-electrode system,the operational voltages of 1.44 and 1.72 V were required to achieve a current density of 10 and 100 mA·cm^(-2) for the overall water splitting test(NiFe LDH-MoS_(x)/INF||20%Pt/C).Additionally,the operational voltage of employing NiFe LDH-MoS_(x)/INF as both cathode and anode merely require 1.52 V at 50mA·cm^(-2) at simulated industrial electrolysis conditions.Notably,a membrane electrode assembly(MEA)for anion exchange membrane water electrolysis(AEMWEs)using NiFe LDH-MoS_(x)/INF as an anode catalyst exhibited an energy conversion efficiency of 71.8%at current density of 400 mA·cm^(-2)in 1 M KOH at 60℃.Further experimental results reveal that sulfurized substrate not only improved the conductivity of NiFe LDH,but also regulated its electronic configurations and atomic composition,leading to the excellent activity.The easy-obtained and cost-effective integrated electrodes are expected to meet the large-scale application of industrial water electrolysis.
文摘Composite membranes and sponge scaffolds consisting chitosan (CS) and acellular derm matrix (ADM) in six ratios were prepared by solvent evaporation technique and freeze-drying method, respectively. The composite materials were characterized by water contact angle measurement, scanning electron microscopy (SEM), water absorption and HaCat cells compatibility. The SEM result showed that CS/ADM three-dimensional (3D) micro-porous structures were successfully produced. The water absorption value of all scaffolds was over 18 times of its initial weight, which is high enough for skin regeneration scaffold, but there were no significant differences of water absorption ratio between deionized water and PBS solution for same scaffold (P > 0.05). HaCat cells were distributed uniformly on the surfaces of membrane 4-6, and an almost confluent monolayer was formed on membrane 6 on the fifth day, whereas cells maintained round and spherical in shape on the surface of membrane 1. The results showed that the cell compatibility of pure CS membrane needed to be improved, and addition of ADM realized this purpose. The results of compatibility of HaCat cells on scaffolds showed that the cell proliferated well on the scaffolds 3 and 4. In our study, the cell’s attachment and growth on the composite membranes was mainly determined by the content of the membrane, whereas the cell’s attachment and growth in the scaffolds was determined by both the content and structure of the scaffolds.
基金supported by the National Natural Science Foundation of China(Grant Nos.61976032 and 62002039)the GenReral Scientific Research Project of Liaoning(No.LJKZ0063).
文摘1 Introduction The k-NN(k Nearest Neighbors)searching problem on road network constitutes a crucial aspect of location-oriented services,which has boasted the practical implications.
基金Ascletis BioScience Co.,Ltd.provided financial support for this study
文摘Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.
基金This work was supported by grants from the National Natural Science Foundation of China （81572766 and 31771630）, the National Key Research and Development Program of China （2017YFA0103800）, Guangdong Innovative and Entrepreneurial Research Team Program （2016ZT06S029）, Guangdong Natural Science Foundation （2016A030313215 and 2016A030313238）, SYSU Young Teachers Training Program （16YKZD14） and grants （CA101795 and IU54CA210181） from U.S. National Cancer Institute, National Institutes of Health （NIH）, DOD （W81XWH-16- 1-0417）, and CPRIT （DP150099, RP170537, and RP150611）.
文摘The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 （PHF20） functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout （KO） for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly（ADP-ribose） polymerase 1 （PARP1） and directly binds to promoter regions of octamer-binding transcription factor 4 （OCT4） and sex determining region Y-box 2 （SOX2） to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit （H3K4me3）. Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.61976032 and 62002039)the General Scientific Research Project of Liaoning(No.LJKZ0063).
文摘1 Introduction With the rapid development of mobile networks,locationbased services has become popular in the daily lives of people.The service providers can recommend the profitable services to persons through mining the frequent interests or places of persons.However,one aspect is that the historical data on Internet can easily cause the leakage of user-relationship privacy,another aspect is that the historical interests of person are always bound to time.Therefore,this paper devotes to study a privacy protection method on time-constrained point of interests(PoIs)based on the group relationships of users.
基金supported by Tulane Weatherhead Endowment Fund (USA)
文摘Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.
