Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexp...Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.展开更多
Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclon...Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.展开更多
OBJECTIVE The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy. METHODS Advanced ...OBJECTIVE The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy. METHODS Advanced cancer patients, all of whom had previously undergone chemotherapy, were randomly divided into 2 groups, one receiving chemotherapy only as the control group, and the other receiving CDA-2 in addition to chemotherapy as the combination group. The therapeutic efficacies and the toxic maniestations of the 2 groups were compared based on the WHO criteria. RESULTS Of 454 cancer patients enrolled in phase Ⅲ clinical trials of CDA-2, 80, 188, and 186 were breast cancer, NSCLC, and primary hepatoma patients, respectively. Among them 378 patients completed treatments according to the protocols. The results showed that the overall effective rate of the combination group was 2.6 fold that of the control group, 4.8 fold in the case of breast cancer, 2.3 fold in the case of primary hepatoma, and 2.2 fold in the case of NSCLC. Surprisingly, the combination therapy appeared to work better for stage Ⅳ than stage Ⅲ patients. CDA-2 did not contribute additional toxicity. On the contrary, it reduced toxic manifestations of chemotherapy, particularly regarding white blood cells, nausea and vomiting. CONCLUSION Modulation of abnormal methylation enzymes by CDA-2 is definitely helpful to supplement chemotherapy. It significantly increased the therapeutic efficacy and reduced the toxic manifestation of cytotoxic chemotherapy on breast cancer and NSCLC.展开更多
Diffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin’s lymphoma(NHL)and has high heterogeneity.Approximately 30%–50%of patients develop relapsed/refractory(R/R)disease,which remains a major cause of mo...Diffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin’s lymphoma(NHL)and has high heterogeneity.Approximately 30%–50%of patients develop relapsed/refractory(R/R)disease,which remains a major cause of mortality1-3.In recent years,a variety of novel therapies have emerged,including bispecific T-cell engagers(BiTEs),antibody–drug conjugates(ADCs),chimeric antigen receptor T cells(CAR-T),and selective BTK inhibitors,which have provided effective treatment strategies for patients with DLBCL1,4.Recently,the 58th Annual Meeting of the American Society of Clinical Oncology(ASCO)was held in Chicago,presenting cutting-edge studies in DLBCL.Here,we discuss a selection of interesting data on this topic.展开更多
OBJECTIVE To study the potential relationship between the expression of PPT-I, NK-1, NK2 and the development of breast cancer cells in bone marrow stroma and to provide evidence of potential molecular mechanisms of br...OBJECTIVE To study the potential relationship between the expression of PPT-I, NK-1, NK2 and the development of breast cancer cells in bone marrow stroma and to provide evidence of potential molecular mechanisms of breast cancer patients. of bone metastasis in early stage METHODS The cocultures of breast cancer cell line T-47D and marrow-derived mesenchymal stem cells (MSC) were established with equal numbers. T-47D cells were separated from the coculture system at 48 h and 96 h after coculture by MACS magnetic cell sorting (MicroBeads). The expression of PPT-I, NK-1, NK-2 in T-47D was then examined before and after coculture by real-time PCR and by Western blot. Alterations in cellular ultrastructure of T-47D cells were detected before and after coculture under electron microscope. Finally, changes in cell cycle distribution were examined by flow cytometry, and growth curves from before and after coculture were drawn and analyzed. RESULTS Following coculture of T-47D and MSC, the expression of PPT-I mRNA and protein was significantly upregulated, while the expression of NK-1 and NK-2 mRNA and protein was greatly downregulated. The analysis of cell cycle distribution by flow cytometry showed that the proportion of T-47D during S phase was increased, and the duration of the G2/M phase was sharply decreased. Under electron microscope, we observed that the synthesis of hereditary material was increased, but the hepatin granules were shown prominent stacking in T-47D cells. These results suggest that although the synthesis of DNA was increased, the proliferation of cells was inhibited after coculture. The cell growth curve confirmed the findings from the observation under the electron microscope and flow cytometry. CONCLUSION Tumor cells could survive through the upregulation in expression of preprotachykinin-I gene during early bone metastasis in breast cancer. The phenomenon of growth suppression in breast cancer cells after coculture in the current study could be induced by downregulation in expression of NK-1 and NK-2.展开更多
This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.go...This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.展开更多
Introduction:The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization(AEFI)using routinely obtained data in China.Four different ...Introduction:The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization(AEFI)using routinely obtained data in China.Four different methods for detecting vaccine safety signals were evaluated.Methods:The AEFI data from 2011 to 2015 was collected for our study.We analyzed the data using four different methods to detect signals:the proportional reporting ratio(PRR),reporting odds ratio(ROR),Bayesian confidence propagation neural network(BCPNN),and multi-item gamma Poisson shrinker(MGPS).Each method was evaluated at 1–3 thresholds for positivity.To assess the performance of these methods,we used the published signal rates as gold standards to determine the sensitivity and specificity.Results:The number of identified signals varied from 602 for PRR1(with a threshold of 1)to 127 for MGPS1.When considering the common reactions as the reference standard,the sensitivity ranged from 0.9%for MGPS1/2 to 38.2%for PRR1/2,and the specificity ranged from 85.2%for PRR1 and ROR1 to 96.7%for MGPS1.When considering the rare reactions as the reference standard,PRR1,PRR2,ROR1,ROR2,and BCPNN exhibited the highest sensitivity(73.3%),while MGPS1 exhibited the highest specificity(96.9%).Discussion:For common reactions,the sensitivities were modest and the specificities were high.For rare reactions,both the sensitivities and specificities were high.Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.展开更多
Introduction:Detecting poliovirus infections proves to be highly challenging due to their asymptomatic nature and infectious potential,highlighting the crucial importance of effective detection methods in the context ...Introduction:Detecting poliovirus infections proves to be highly challenging due to their asymptomatic nature and infectious potential,highlighting the crucial importance of effective detection methods in the context of polio eradication efforts.In many countries,including China,the primary approach for identifying polio outbreaks has been through acute flaccid paralysis(AFP)surveillance.In this study,we conducted an evaluation spanning three decades(1993–2022)to assess the effectiveness of AFP surveillance in China.Methods:Data on all AFP cases identified since 1993 and national-level AFP surveillance system quality indicators aligned with the World Health Organization(WHO)standards were collected for analysis.The quality indicators assess surveillance sensitivity,completeness,timeliness of detection notification,case investigation,and laboratory workup.Surveillance sensitivity is determined by the non-polio AFP(NPAFP)detection rate among children under 15 years of age.Results:Between 1993 and 2022,a total of 150,779 AFP cases were identified and reported.Within this pool,surveillance identified 95 cases of wild poliovirus(WPV)and 24 cases due to vaccinederived poliovirus.From 1995 onwards,the detection rate of NPAFP cases consistently adhered to the WHO and national standards of≥1 case per 100,000,falling between 1.38 and 2.76.Starting in 1997,all timeliness indicators consistently achieved the criteria of 80%,apart from the consistency in meeting standards set for the rate of positive specimens sent to the national laboratory.Conclusions:AFP surveillance has been instrumental in China’s accomplishment of maintaining a polio-free status.The ongoing adherence to key performance indicators,ensuring sensitivity and prompt specimen collection,demonstrates that AFP surveillance is proficient in detecting poliovirus in China.As we move into the post-eradication phase,AFP surveillance remains crucial for the sustained absence of polioviruses in the long term.展开更多
What is already known about this topic?The incidences of vaccine-preventable diseases(VPDs)included in the Expanded Program on Immunization in China have decreased significantly in recent decades.What is added by this...What is already known about this topic?The incidences of vaccine-preventable diseases(VPDs)included in the Expanded Program on Immunization in China have decreased significantly in recent decades.What is added by this report?This study summarizes the national incidences of nine VPDs and the seroprevalence of hepatitis B surface antigen(HBsAg)under different immunization strategies from 1950 through 2021 in China.The sharpest decreases in VPD incidence and under-5-year HBsAg seroprevalence occurred during the latest stage of the National Immunization Program.The decreases in VPD incidence were most prominent among children under five years of age.What are the implications for public health practice?These findings provide valuable insights for vaccine value assessment and emphasize the importance of implementing immunization strategies in targeted populations.展开更多
Real-world study(RWS)gained prominence starting with a significant investigation on ramipril’s impact on hypertension in 1993(1).A key advancement for the Food and Drug Administration(FDA)occurred with the enactment ...Real-world study(RWS)gained prominence starting with a significant investigation on ramipril’s impact on hypertension in 1993(1).A key advancement for the Food and Drug Administration(FDA)occurred with the enactment of the 21st Century Cures Act in 2016,emphasizing RWS(2).The FDA’s Real-world Evidence Program establishes real-world data(RWD)as“data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources”,while real-world evidence(RWE)is“clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD”(3).The proliferation of big data,electronic medical records(EMR),electronic health records(EHR),and medical claims data offers vast information resources facilitating RWS.Enhanced access to RWD allows for worldwide monitoring of the impacts of various public health initiatives like vaccination programs.While randomized clinical trials(RCTs)traditionally gauge vaccine efficacy and shortterm safety,RWS can assess vaccine performance and safety across larger,more diverse populations and are adept at identifying rare events not easily discernible in RCTs due to their infrequency.展开更多
Measles,an acute respiratory infectious disease caused by the measles virus,was responsible for millions of deaths annually before the introduction of the measles vaccine(MV)(1).Widespread availability of measles vacc...Measles,an acute respiratory infectious disease caused by the measles virus,was responsible for millions of deaths annually before the introduction of the measles vaccine(MV)(1).Widespread availability of measles vaccines and the initiation of the Expanded Program on Immunization,approved at the 27th World Health Assembly in 1974(2),have significantly improved global measles control.In China,measles has been a statutorily notifiable disease since the establishment of the National Notifiable Diseases Reporting System(NNDRS)in 1950(3).展开更多
Summary What is already known on this topic?Chronic obstructive pulmonary disease(COPD)exacerbations increase household economic burden,but there is limited evidence from prospective cohort studies in China about the ...Summary What is already known on this topic?Chronic obstructive pulmonary disease(COPD)exacerbations increase household economic burden,but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden.What is added by this report?This study demonstrated the economic burden of COPD exacerbations,pneumonia,and hospitalization in COPD patients in China is substantial.Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine(PPSV23),separately or together,were significantly associated with decreased economic burden.What are the implications for public health practice?Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.展开更多
In an offshore wind farm,a high‐voltage switchgear interruption in an offshore substation creates a high‐frequency,high‐amplitude overvoltage that can cause severe electromagnetic interference problems in the intel...In an offshore wind farm,a high‐voltage switchgear interruption in an offshore substation creates a high‐frequency,high‐amplitude overvoltage that can cause severe electromagnetic interference problems in the intelligent electronic device.To address this issue,mathematical models,vector fitting and finite element method were used to build an integrated electromagnetic disturbance conduction model,whose accuracy was verified by large current interruption tests.Through the simulation of a typical offshore wind farm's single‐phase grounding fault interruption process,the electromagnetic disturbance characteristics and the impact of the ground position are obtained.The results show that during the fault interruption process of phase B grounded,the dominant frequency of disturbance voltage can reach 4.34 MHz,and the amplitude can reach 1.12 kV.The ground grid has a large impact on the interference voltage,which can reach a maximum value of 2.28 kV under specific conditions.The disturbance voltage in the fault process mainly comes through the current transformer,while during the interruption process,it mainly comes through the ground grid.The authors provide a method to establish the integrated electromagnetic disturbance simulation model,which can improve the accuracy of the electromagnetic disturbance conduction process simulation of intelligent components.展开更多
Sparse signal is a kind of sparse matrices which can carry fault information and simplify the signal at the same time.This can effectively reduce the cost of signal storage,improve the efficiency of data transmission,...Sparse signal is a kind of sparse matrices which can carry fault information and simplify the signal at the same time.This can effectively reduce the cost of signal storage,improve the efficiency of data transmission,and ultimately save the cost of equipment fault diagnosis in the aviation field.At present,the existing sparse decomposition methods generally extract sparse fault characteristics signals based on orthogonal basis atoms,which limits the adaptability of sparse decomposition.In this paper,a self-adaptive atom is extracted by the improved dual-channel tunable Q-factor wavelet transform(TQWT)method to construct a self-adaptive complete dictionary.Finally,the sparse signal is obtained by the orthogonal matching pursuit(OMP)algorithm.The atoms obtained by this method are more flexible,and are no longer constrained to an orthogonal basis to reflect the oscillation characteristics of signals.Therefore,the sparse signal can better extract the fault characteristics.The simulation and experimental results show that the selfadaptive dictionary with the atom extracted from the dual-channel TQWT has a stronger decomposition freedom and signal matching ability than orthogonal basis dictionaries,such as discrete cosine transform(DCT),discrete Hartley transform(DHT)and discrete wavelet transform(DWT).In addition,the sparse signal extracted by the self-adaptive complete dictionary can reflect the time-domain characteristics of the vibration signals,and can more accurately extract the bearing fault feature frequency.展开更多
Introduction:In the early stages of the coronavirus disease 2019(COVID-19)epidemic in China,the highest level of public health emergency response(Level 1 Response)was launched in all province-level administrative divi...Introduction:In the early stages of the coronavirus disease 2019(COVID-19)epidemic in China,the highest level of public health emergency response(Level 1 Response)was launched in all province-level administrative divisions(PLADs)across the country.Provision of vaccination services was selectively suspended due to the physical distancing and gathering restrictions required of Level 1 Response.The purpose of this paper is to evaluate the impact of COVID-19 on vaccination services and the effectiveness of selective vaccination service suspension and catch-up vaccinations in China.Methods:Vaccine doses administered,routine vaccination coverage levels,catch-up vaccine doses administered,and coverage levels after the catch-up campaign were determined from individual vaccination records in sampled clinics,standard routine immunization administrative coverage reports,and catch-up vaccination activity reports submitted by PLADs between October 2019 and October 2020.Results:National Immunization Program(NIP)and non-NIP vaccine doses administered in sampled clinics decreased by 80% and 90%,respectively,compared with doses administered before the COVID-19 pandemic.Coverage with the birth dose of hepatitis B vaccine(HepB1)and the Bacillus Calmette-Guérin vaccine(BCG)—two vaccinations recommended to continue throughout the epidemic due to their timecritical nature—were maintained at over 85%,while coverage of other NIP vaccines decreased to below 60%by February 2020.Catch-up vaccination coverage of the 29 PLADs,excluding Xinjiang and Xizang(Tibet),began in April 2020 and exceeded 90%;Hubei catch-up coverage was 95% by October 2020.Conclusions and Implications for Public Health Practice:The COVID-19 pandemic had a great impact on China’s vaccination services.During the epidemic and time of local transmission of the coronavirus,HepB1,BCG,rabies vaccine for postexposure prophylaxis,and tetanus antitoxin(TAT)for wound prophylaxis were maintained at high levels.Of the 69 million vaccine doses postponed during the time of local transmission of the coronavirus,94% were administered in the catch-up campaign.China’s pandemic immunization practices may provide evidence for other countries’immunization programs.展开更多
Based on the finite deformation theory of the continuum and poroelastic theory, the aeoustoelastic theory for fluid-saturated porous media (FSPM) in natural and initial coordi- nates is developed to investigate the ...Based on the finite deformation theory of the continuum and poroelastic theory, the aeoustoelastic theory for fluid-saturated porous media (FSPM) in natural and initial coordi- nates is developed to investigate the influence of effective stresses and fluid pore pressure on wave velocities. Firstly, the assumption of a small dynamic motion superimposed on a largely static pre- deformation of the FSPM yields natural, initial, and final configurations, whose displacements, strains, and stresses of the solid-skeleton and the fluid in an FSPM particle could be described in natural and initial coordinates, respectively. Secondly, the subtraction of initial-state equations of equilibrium from the final-state equations of motion and the introduction of non-linear constitu- rive relations of the FSPM lead to equations of motion for the small dynamic motion. Thirdly, the consideration of homogeneous pre-deformation and the plane harmonic form of the small dynamic motion gives an acoustoelastic equation, which provides analytical formulations for the relation of the fast longitudinal wave, the fast shear wave, the slow shear wave, and the slow longitudinal wave with solid-skeleton stresses and fluid pore-pressure. Lastly, an isotropic FSPM under the close-pore jacketed condition, open-pore jacketed condition, traditional unjacketed condition, and triaxial condition is taken as an example to discuss the velocities of the fast and slow shear waves propagating along the direction of one of the initial principal solid-skeleton strains. The detailed discussion shows that the wave velocities of the FSPM are usually influenced by the effective stresses and the fluid pore pressure. The fluid pore-pressure has little effect on the wave velocities of the FSPM only when the components of the applied initial principal solid-skeleton stresses or strains are equal, which is consistent with the previous experimental results.展开更多
The effects of porous media grain size distribution on the transport and deposition of polydisperse suspended particles under different flow velocities were investigated. Selected Kaolinite particles (2-30 μm) and ...The effects of porous media grain size distribution on the transport and deposition of polydisperse suspended particles under different flow velocities were investigated. Selected Kaolinite particles (2-30 μm) and Fluorescein (dissolved tracer) were injected in the porous media by step input injection technique. Three sands filled columns were used: Fine sand, Coarse sand, and a third sand (Mixture) obtained by mixing the two last sands in equal weight proportion. The porous media performance on the particle removal was evaluated by analysing particles breakthrough curves, hydro-dispersive parameters determined using the analytical solution of convection-dispersion equation with a first order deposition kinetics, particles deposition profiles, and particle-size distribution of the recovered and the deposited particles. The deposition kinetics and the longitudinal hydrodynamic dispersion coefficients are controlled by the porous media grain size distribution. Mixture sand is more dispersive than Fine and Coarse sands. More the uniformity coefficient of the porous medium is large, higher is the filtration efficiency. At low velocities, porous media capture all sizes of suspended particles injected with larger ones mainly captured at the entrance. A high flow velocity carries the particles deeper into the porous media, producing more gradual changes in the deposition profile. The median diameter of the deposited particles at different depth increases with flow velocity. The large grain size distribution leads to build narrow pores enhancing the deposition of the particles by straining.展开更多
What is already known about this topic?After the type 2 strain of the live,attenuated poliovirus vaccine was withdrawn globally in 2016,any identification of a type 2 poliovirus is a Public Health Emergency of Interna...What is already known about this topic?After the type 2 strain of the live,attenuated poliovirus vaccine was withdrawn globally in 2016,any identification of a type 2 poliovirus is a Public Health Emergency of International Concern.A vaccinederived type 2 poliovirus(VDPV2)was identified in Sichuan,prompting an urgent,comprehensive investigation and response.What is added by this report?Type 2 monovalent,live,attenuated oral poliovirus vaccine(mOPV2)is being used to respond to the numerous VDPV2 outbreaks seen around the world.In contrast,the response in Sichuan used Sabin strain inactivated poliovirus(sIPV)to stop circulation of the VDPV2.In the 6 months following the vaccination response,there have been no VDPV2s detected in Sichuan,despite extensive search.What are the implications for public health practices?Further search for the VDPV2 must continue in order to determine whether transmission has been stopped.The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.展开更多
What is already known about this topic?China has historically had high measles incidence and many associated deaths.A comprehensive measles elimination plan during 2006-2012 substantially reduced measles incidence;how...What is already known about this topic?China has historically had high measles incidence and many associated deaths.A comprehensive measles elimination plan during 2006-2012 substantially reduced measles incidence;however,a resurgence occurred during 2013-2015.What is added by this report?In China,measles surveillance,outbreak response,research,and program evaluation were used to strengthen routine immunization and target immunization activities for eliminating measles.Measles incidence declined from 31 per million in 2015 to 2.8 in 2018;only one measles-associated death has been reported during 2018-June 2019.What are the implications for public health practice?The World Health Organization-recommended strategy to eliminate measles can be effective,including in large,densely populated countries like China.展开更多
In late December 2019,clinicians in Hubei Province noticed and reported to health authorities a cluster of cases of pneumonia of unknown etiology(PUE)that turned out to be the start of the coronavirus disease 2019(COV...In late December 2019,clinicians in Hubei Province noticed and reported to health authorities a cluster of cases of pneumonia of unknown etiology(PUE)that turned out to be the start of the coronavirus disease 2019(COVID-19)pandemic(1).By January 29,2020,all provincial-level administrative divisions(PLADs)across the country had launched their highest public health emergency responses(Level 1 responses)(2-3).展开更多
基金supported by a grant from the National Natural Science Foundation of China (Grant No.81372539)
文摘Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.
基金funded by Sinocelltech Ltd, Beijing Chinapartly supported by China National Major Project for New Drug Innovation (No. 2012ZX09303012 and No. 2017ZX09304015)
文摘Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.
文摘OBJECTIVE The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy. METHODS Advanced cancer patients, all of whom had previously undergone chemotherapy, were randomly divided into 2 groups, one receiving chemotherapy only as the control group, and the other receiving CDA-2 in addition to chemotherapy as the combination group. The therapeutic efficacies and the toxic maniestations of the 2 groups were compared based on the WHO criteria. RESULTS Of 454 cancer patients enrolled in phase Ⅲ clinical trials of CDA-2, 80, 188, and 186 were breast cancer, NSCLC, and primary hepatoma patients, respectively. Among them 378 patients completed treatments according to the protocols. The results showed that the overall effective rate of the combination group was 2.6 fold that of the control group, 4.8 fold in the case of breast cancer, 2.3 fold in the case of primary hepatoma, and 2.2 fold in the case of NSCLC. Surprisingly, the combination therapy appeared to work better for stage Ⅳ than stage Ⅲ patients. CDA-2 did not contribute additional toxicity. On the contrary, it reduced toxic manifestations of chemotherapy, particularly regarding white blood cells, nausea and vomiting. CONCLUSION Modulation of abnormal methylation enzymes by CDA-2 is definitely helpful to supplement chemotherapy. It significantly increased the therapeutic efficacy and reduced the toxic manifestation of cytotoxic chemotherapy on breast cancer and NSCLC.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82070206)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-053B).
文摘Diffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin’s lymphoma(NHL)and has high heterogeneity.Approximately 30%–50%of patients develop relapsed/refractory(R/R)disease,which remains a major cause of mortality1-3.In recent years,a variety of novel therapies have emerged,including bispecific T-cell engagers(BiTEs),antibody–drug conjugates(ADCs),chimeric antigen receptor T cells(CAR-T),and selective BTK inhibitors,which have provided effective treatment strategies for patients with DLBCL1,4.Recently,the 58th Annual Meeting of the American Society of Clinical Oncology(ASCO)was held in Chicago,presenting cutting-edge studies in DLBCL.Here,we discuss a selection of interesting data on this topic.
基金supported by a grant from the National Natural Science Foundation of China(No.30670802).
文摘OBJECTIVE To study the potential relationship between the expression of PPT-I, NK-1, NK2 and the development of breast cancer cells in bone marrow stroma and to provide evidence of potential molecular mechanisms of breast cancer patients. of bone metastasis in early stage METHODS The cocultures of breast cancer cell line T-47D and marrow-derived mesenchymal stem cells (MSC) were established with equal numbers. T-47D cells were separated from the coculture system at 48 h and 96 h after coculture by MACS magnetic cell sorting (MicroBeads). The expression of PPT-I, NK-1, NK-2 in T-47D was then examined before and after coculture by real-time PCR and by Western blot. Alterations in cellular ultrastructure of T-47D cells were detected before and after coculture under electron microscope. Finally, changes in cell cycle distribution were examined by flow cytometry, and growth curves from before and after coculture were drawn and analyzed. RESULTS Following coculture of T-47D and MSC, the expression of PPT-I mRNA and protein was significantly upregulated, while the expression of NK-1 and NK-2 mRNA and protein was greatly downregulated. The analysis of cell cycle distribution by flow cytometry showed that the proportion of T-47D during S phase was increased, and the duration of the G2/M phase was sharply decreased. Under electron microscope, we observed that the synthesis of hereditary material was increased, but the hepatin granules were shown prominent stacking in T-47D cells. These results suggest that although the synthesis of DNA was increased, the proliferation of cells was inhibited after coculture. The cell growth curve confirmed the findings from the observation under the electron microscope and flow cytometry. CONCLUSION Tumor cells could survive through the upregulation in expression of preprotachykinin-I gene during early bone metastasis in breast cancer. The phenomenon of growth suppression in breast cancer cells after coculture in the current study could be induced by downregulation in expression of NK-1 and NK-2.
基金This study was sponsored by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.(Nanjing,China)and was supported by grants from National Natural Science Foundation of China(Grant Number,81872902,82073917,and 82070206)National Natural Science Foundation of Guangdong Province(Grant Number,2023A1515011525)+1 种基金The Lymphoma Research Fund of China Anti-Cancer Association,and the Sun Yat-sen University Cancer Center Clinical Research 308 Program(Grant Number,2014-fxy-106 and 2016-fxy-079)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant Number,TJYXZDXK-053B).
文摘This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.
基金Supported by the Beijing Natural Science Foundation(L212058).
文摘Introduction:The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization(AEFI)using routinely obtained data in China.Four different methods for detecting vaccine safety signals were evaluated.Methods:The AEFI data from 2011 to 2015 was collected for our study.We analyzed the data using four different methods to detect signals:the proportional reporting ratio(PRR),reporting odds ratio(ROR),Bayesian confidence propagation neural network(BCPNN),and multi-item gamma Poisson shrinker(MGPS).Each method was evaluated at 1–3 thresholds for positivity.To assess the performance of these methods,we used the published signal rates as gold standards to determine the sensitivity and specificity.Results:The number of identified signals varied from 602 for PRR1(with a threshold of 1)to 127 for MGPS1.When considering the common reactions as the reference standard,the sensitivity ranged from 0.9%for MGPS1/2 to 38.2%for PRR1/2,and the specificity ranged from 85.2%for PRR1 and ROR1 to 96.7%for MGPS1.When considering the rare reactions as the reference standard,PRR1,PRR2,ROR1,ROR2,and BCPNN exhibited the highest sensitivity(73.3%),while MGPS1 exhibited the highest specificity(96.9%).Discussion:For common reactions,the sensitivities were modest and the specificities were high.For rare reactions,both the sensitivities and specificities were high.Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.
基金Supported by the public health emergency response mechanism operated by the Chinese Center for Disease Control and Prevention(No.102393220020010000017).
文摘Introduction:Detecting poliovirus infections proves to be highly challenging due to their asymptomatic nature and infectious potential,highlighting the crucial importance of effective detection methods in the context of polio eradication efforts.In many countries,including China,the primary approach for identifying polio outbreaks has been through acute flaccid paralysis(AFP)surveillance.In this study,we conducted an evaluation spanning three decades(1993–2022)to assess the effectiveness of AFP surveillance in China.Methods:Data on all AFP cases identified since 1993 and national-level AFP surveillance system quality indicators aligned with the World Health Organization(WHO)standards were collected for analysis.The quality indicators assess surveillance sensitivity,completeness,timeliness of detection notification,case investigation,and laboratory workup.Surveillance sensitivity is determined by the non-polio AFP(NPAFP)detection rate among children under 15 years of age.Results:Between 1993 and 2022,a total of 150,779 AFP cases were identified and reported.Within this pool,surveillance identified 95 cases of wild poliovirus(WPV)and 24 cases due to vaccinederived poliovirus.From 1995 onwards,the detection rate of NPAFP cases consistently adhered to the WHO and national standards of≥1 case per 100,000,falling between 1.38 and 2.76.Starting in 1997,all timeliness indicators consistently achieved the criteria of 80%,apart from the consistency in meeting standards set for the rate of positive specimens sent to the national laboratory.Conclusions:AFP surveillance has been instrumental in China’s accomplishment of maintaining a polio-free status.The ongoing adherence to key performance indicators,ensuring sensitivity and prompt specimen collection,demonstrates that AFP surveillance is proficient in detecting poliovirus in China.As we move into the post-eradication phase,AFP surveillance remains crucial for the sustained absence of polioviruses in the long term.
基金Supported by Operation of the CDC Public Health Emergency Response Mechanism in China(131031001000150001).
文摘What is already known about this topic?The incidences of vaccine-preventable diseases(VPDs)included in the Expanded Program on Immunization in China have decreased significantly in recent decades.What is added by this report?This study summarizes the national incidences of nine VPDs and the seroprevalence of hepatitis B surface antigen(HBsAg)under different immunization strategies from 1950 through 2021 in China.The sharpest decreases in VPD incidence and under-5-year HBsAg seroprevalence occurred during the latest stage of the National Immunization Program.The decreases in VPD incidence were most prominent among children under five years of age.What are the implications for public health practice?These findings provide valuable insights for vaccine value assessment and emphasize the importance of implementing immunization strategies in targeted populations.
文摘Real-world study(RWS)gained prominence starting with a significant investigation on ramipril’s impact on hypertension in 1993(1).A key advancement for the Food and Drug Administration(FDA)occurred with the enactment of the 21st Century Cures Act in 2016,emphasizing RWS(2).The FDA’s Real-world Evidence Program establishes real-world data(RWD)as“data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources”,while real-world evidence(RWE)is“clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD”(3).The proliferation of big data,electronic medical records(EMR),electronic health records(EHR),and medical claims data offers vast information resources facilitating RWS.Enhanced access to RWD allows for worldwide monitoring of the impacts of various public health initiatives like vaccination programs.While randomized clinical trials(RCTs)traditionally gauge vaccine efficacy and shortterm safety,RWS can assess vaccine performance and safety across larger,more diverse populations and are adept at identifying rare events not easily discernible in RCTs due to their infrequency.
文摘Measles,an acute respiratory infectious disease caused by the measles virus,was responsible for millions of deaths annually before the introduction of the measles vaccine(MV)(1).Widespread availability of measles vaccines and the initiation of the Expanded Program on Immunization,approved at the 27th World Health Assembly in 1974(2),have significantly improved global measles control.In China,measles has been a statutorily notifiable disease since the establishment of the National Notifiable Diseases Reporting System(NNDRS)in 1950(3).
基金National Key R&D Program of China(2017YFC1309304).
文摘Summary What is already known on this topic?Chronic obstructive pulmonary disease(COPD)exacerbations increase household economic burden,but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden.What is added by this report?This study demonstrated the economic burden of COPD exacerbations,pneumonia,and hospitalization in COPD patients in China is substantial.Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine(PPSV23),separately or together,were significantly associated with decreased economic burden.What are the implications for public health practice?Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.
基金National Key R&D Program of China,Grant/Award Number:2017YFB0902400。
文摘In an offshore wind farm,a high‐voltage switchgear interruption in an offshore substation creates a high‐frequency,high‐amplitude overvoltage that can cause severe electromagnetic interference problems in the intelligent electronic device.To address this issue,mathematical models,vector fitting and finite element method were used to build an integrated electromagnetic disturbance conduction model,whose accuracy was verified by large current interruption tests.Through the simulation of a typical offshore wind farm's single‐phase grounding fault interruption process,the electromagnetic disturbance characteristics and the impact of the ground position are obtained.The results show that during the fault interruption process of phase B grounded,the dominant frequency of disturbance voltage can reach 4.34 MHz,and the amplitude can reach 1.12 kV.The ground grid has a large impact on the interference voltage,which can reach a maximum value of 2.28 kV under specific conditions.The disturbance voltage in the fault process mainly comes through the current transformer,while during the interruption process,it mainly comes through the ground grid.The authors provide a method to establish the integrated electromagnetic disturbance simulation model,which can improve the accuracy of the electromagnetic disturbance conduction process simulation of intelligent components.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFB1503103).
文摘Sparse signal is a kind of sparse matrices which can carry fault information and simplify the signal at the same time.This can effectively reduce the cost of signal storage,improve the efficiency of data transmission,and ultimately save the cost of equipment fault diagnosis in the aviation field.At present,the existing sparse decomposition methods generally extract sparse fault characteristics signals based on orthogonal basis atoms,which limits the adaptability of sparse decomposition.In this paper,a self-adaptive atom is extracted by the improved dual-channel tunable Q-factor wavelet transform(TQWT)method to construct a self-adaptive complete dictionary.Finally,the sparse signal is obtained by the orthogonal matching pursuit(OMP)algorithm.The atoms obtained by this method are more flexible,and are no longer constrained to an orthogonal basis to reflect the oscillation characteristics of signals.Therefore,the sparse signal can better extract the fault characteristics.The simulation and experimental results show that the selfadaptive dictionary with the atom extracted from the dual-channel TQWT has a stronger decomposition freedom and signal matching ability than orthogonal basis dictionaries,such as discrete cosine transform(DCT),discrete Hartley transform(DHT)and discrete wavelet transform(DWT).In addition,the sparse signal extracted by the self-adaptive complete dictionary can reflect the time-domain characteristics of the vibration signals,and can more accurately extract the bearing fault feature frequency.
基金funded by grants from the Vaccine Preventable Diseases and Immunization(VDI)of World Health Organization Office in China(No.2020/1017283-0).
文摘Introduction:In the early stages of the coronavirus disease 2019(COVID-19)epidemic in China,the highest level of public health emergency response(Level 1 Response)was launched in all province-level administrative divisions(PLADs)across the country.Provision of vaccination services was selectively suspended due to the physical distancing and gathering restrictions required of Level 1 Response.The purpose of this paper is to evaluate the impact of COVID-19 on vaccination services and the effectiveness of selective vaccination service suspension and catch-up vaccinations in China.Methods:Vaccine doses administered,routine vaccination coverage levels,catch-up vaccine doses administered,and coverage levels after the catch-up campaign were determined from individual vaccination records in sampled clinics,standard routine immunization administrative coverage reports,and catch-up vaccination activity reports submitted by PLADs between October 2019 and October 2020.Results:National Immunization Program(NIP)and non-NIP vaccine doses administered in sampled clinics decreased by 80% and 90%,respectively,compared with doses administered before the COVID-19 pandemic.Coverage with the birth dose of hepatitis B vaccine(HepB1)and the Bacillus Calmette-Guérin vaccine(BCG)—two vaccinations recommended to continue throughout the epidemic due to their timecritical nature—were maintained at over 85%,while coverage of other NIP vaccines decreased to below 60%by February 2020.Catch-up vaccination coverage of the 29 PLADs,excluding Xinjiang and Xizang(Tibet),began in April 2020 and exceeded 90%;Hubei catch-up coverage was 95% by October 2020.Conclusions and Implications for Public Health Practice:The COVID-19 pandemic had a great impact on China’s vaccination services.During the epidemic and time of local transmission of the coronavirus,HepB1,BCG,rabies vaccine for postexposure prophylaxis,and tetanus antitoxin(TAT)for wound prophylaxis were maintained at high levels.Of the 69 million vaccine doses postponed during the time of local transmission of the coronavirus,94% were administered in the catch-up campaign.China’s pandemic immunization practices may provide evidence for other countries’immunization programs.
基金supported by the National Natural Science Foundation of China(No.11072224)research grantsfrom Institute of Crustal Dynamics(No.ZDJ2012-20) and overseas-returned scholar,Personnel Ministry of China
文摘Based on the finite deformation theory of the continuum and poroelastic theory, the aeoustoelastic theory for fluid-saturated porous media (FSPM) in natural and initial coordi- nates is developed to investigate the influence of effective stresses and fluid pore pressure on wave velocities. Firstly, the assumption of a small dynamic motion superimposed on a largely static pre- deformation of the FSPM yields natural, initial, and final configurations, whose displacements, strains, and stresses of the solid-skeleton and the fluid in an FSPM particle could be described in natural and initial coordinates, respectively. Secondly, the subtraction of initial-state equations of equilibrium from the final-state equations of motion and the introduction of non-linear constitu- rive relations of the FSPM lead to equations of motion for the small dynamic motion. Thirdly, the consideration of homogeneous pre-deformation and the plane harmonic form of the small dynamic motion gives an acoustoelastic equation, which provides analytical formulations for the relation of the fast longitudinal wave, the fast shear wave, the slow shear wave, and the slow longitudinal wave with solid-skeleton stresses and fluid pore-pressure. Lastly, an isotropic FSPM under the close-pore jacketed condition, open-pore jacketed condition, traditional unjacketed condition, and triaxial condition is taken as an example to discuss the velocities of the fast and slow shear waves propagating along the direction of one of the initial principal solid-skeleton strains. The detailed discussion shows that the wave velocities of the FSPM are usually influenced by the effective stresses and the fluid pore pressure. The fluid pore-pressure has little effect on the wave velocities of the FSPM only when the components of the applied initial principal solid-skeleton stresses or strains are equal, which is consistent with the previous experimental results.
基金supported by Région Haute Normandie(CPER)_R2014-CPER-0094
文摘The effects of porous media grain size distribution on the transport and deposition of polydisperse suspended particles under different flow velocities were investigated. Selected Kaolinite particles (2-30 μm) and Fluorescein (dissolved tracer) were injected in the porous media by step input injection technique. Three sands filled columns were used: Fine sand, Coarse sand, and a third sand (Mixture) obtained by mixing the two last sands in equal weight proportion. The porous media performance on the particle removal was evaluated by analysing particles breakthrough curves, hydro-dispersive parameters determined using the analytical solution of convection-dispersion equation with a first order deposition kinetics, particles deposition profiles, and particle-size distribution of the recovered and the deposited particles. The deposition kinetics and the longitudinal hydrodynamic dispersion coefficients are controlled by the porous media grain size distribution. Mixture sand is more dispersive than Fine and Coarse sands. More the uniformity coefficient of the porous medium is large, higher is the filtration efficiency. At low velocities, porous media capture all sizes of suspended particles injected with larger ones mainly captured at the entrance. A high flow velocity carries the particles deeper into the porous media, producing more gradual changes in the deposition profile. The median diameter of the deposited particles at different depth increases with flow velocity. The large grain size distribution leads to build narrow pores enhancing the deposition of the particles by straining.
基金supported by National Science and Technology Major Project of China(2018ZX10101002-003).
文摘What is already known about this topic?After the type 2 strain of the live,attenuated poliovirus vaccine was withdrawn globally in 2016,any identification of a type 2 poliovirus is a Public Health Emergency of International Concern.A vaccinederived type 2 poliovirus(VDPV2)was identified in Sichuan,prompting an urgent,comprehensive investigation and response.What is added by this report?Type 2 monovalent,live,attenuated oral poliovirus vaccine(mOPV2)is being used to respond to the numerous VDPV2 outbreaks seen around the world.In contrast,the response in Sichuan used Sabin strain inactivated poliovirus(sIPV)to stop circulation of the VDPV2.In the 6 months following the vaccination response,there have been no VDPV2s detected in Sichuan,despite extensive search.What are the implications for public health practices?Further search for the VDPV2 must continue in order to determine whether transmission has been stopped.The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.
文摘What is already known about this topic?China has historically had high measles incidence and many associated deaths.A comprehensive measles elimination plan during 2006-2012 substantially reduced measles incidence;however,a resurgence occurred during 2013-2015.What is added by this report?In China,measles surveillance,outbreak response,research,and program evaluation were used to strengthen routine immunization and target immunization activities for eliminating measles.Measles incidence declined from 31 per million in 2015 to 2.8 in 2018;only one measles-associated death has been reported during 2018-June 2019.What are the implications for public health practice?The World Health Organization-recommended strategy to eliminate measles can be effective,including in large,densely populated countries like China.
文摘In late December 2019,clinicians in Hubei Province noticed and reported to health authorities a cluster of cases of pneumonia of unknown etiology(PUE)that turned out to be the start of the coronavirus disease 2019(COVID-19)pandemic(1).By January 29,2020,all provincial-level administrative divisions(PLADs)across the country had launched their highest public health emergency responses(Level 1 responses)(2-3).