IN March 2018, the United States slapped tariffs of 25 percent on steel imports and 10 percent on aluminum in the name of national security under Section 232 of the Trade Expansion Act of 1962. Then, the Office of the...IN March 2018, the United States slapped tariffs of 25 percent on steel imports and 10 percent on aluminum in the name of national security under Section 232 of the Trade Expansion Act of 1962. Then, the Office of the United States Trade Representative released a report on the investigation of China under Section 301 of the Trade Act of 1974, claiming China's acts, policies, and practices regarding technology transfer, intellectual property, and innovation are “unreasonable and discriminatory, and burden U.S. commerce.”展开更多
1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Part...1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Partial hepatectomy is recommended for patients with early stage HCC.[2]A large proportion of patients with HCC inChina are diagnosed in the intermediate to advanced HCC stages,rendering them ineligible for hepatectomy due to aspects such as liver dysfunction,insufficient residual liver volume,or surgical technique.展开更多
Emergency medical services (EMS) are a vital element of the public healthcare system in China,^([1])providing an opportunity to respond to critical medical conditions and save people’s lives.^([2])The accessibility o...Emergency medical services (EMS) are a vital element of the public healthcare system in China,^([1])providing an opportunity to respond to critical medical conditions and save people’s lives.^([2])The accessibility of EMS has received considerable attention in health and transport geography studies.^([3])One of the optimal gauges for evaluating the accessibility of EMS is the response time,which is defined as the time from receiving an emergency call to the arrival of an ambulance.^([4])Beijing has already reduced the response time to approximately12 min,and the next goal is to ensure that the response time across Beijing does not exceed 12 min (the information comes from the Beijing Emergency Medical Center).展开更多
Optogenetics,a technique that employs light for neuromodulation,has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type spe...Optogenetics,a technique that employs light for neuromodulation,has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type specificity.However,visible light,particularly blue and green light,commonly used in conventional optogenetics,has limited penetration in biological tissue.This limitation necessitates the implantation of optical fibers for light delivery,especially in deep brain regions,leading to tissue damage and experimental constraints.To overcome these challenges,the use of orange-red and infrared light with greater tissue penetration has emerged as a promising approach for tetherless optical neuromodulation.In this review,we provide an overview of the development and applications of tetherless optical neuromodulation methods with long wavelengths.We first discuss the exploration of orange-red wavelength-responsive rhodopsins and their performance in tetherless optical neuromodulation.Then,we summarize two novel tetherless neuromodulation methods using near-infrared light:upconversion nanoparticle-mediated optogenetics and photothermal neuromodulation.In addition,we discuss recent advances in mid-infrared optical neuromodulation.展开更多
Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical...Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.展开更多
Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet...Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.展开更多
The judicial application of digital evidence in criminal cases(criminal digital evidence)is an inevitable trend for the digital transformation of criminal proceedings in the macro context of the digital economy.It is ...The judicial application of digital evidence in criminal cases(criminal digital evidence)is an inevitable trend for the digital transformation of criminal proceedings in the macro context of the digital economy.It is characterized by digitization,diversification,and traceability.The application of criminal digital evidence can be divided into two main scenarios:the vertical scenario involving phases such as filing,prosecution,and trial;the horizontal scenario related to specific types of crimes.Criminal digital evidence is primarily applied to handling non-contact crimes,such as cybercrimes.However,the application of such evidence may infringe upon the basic rights of suspects,including their rights to privacy,rights to know,and rights to defense.Furthermore,the diversified and non-systematic nature of digital evidence may lead to challenges in applying the law,particularly with algorithmic“black boxes,”which can result in judicial discrimination and other drawbacks.Therefore,it is necessary to formulate or improve the regulatory framework for criminal digital evidence to ensure its lawful and standardized application.Additionally,judicial authorities must strengthen collaboration in case handling to ensure smooth coordination in collecting and applying digital evidence,thereby realizing its efficient litigation value.Furthermore,it is essential to check and balance the algorithm-based conviction and sentencing to protect the legitimate rights and interests of the parties involved,achieving high-quality human rights protection.展开更多
BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the dif...BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.展开更多
[Objective]The aim was to study the sensitive response characteristics of the main agronomic traits of somaclonal and the variation of sensitive response of the lines of somaclonal to sowing date. [Method]The RITSD ch...[Objective]The aim was to study the sensitive response characteristics of the main agronomic traits of somaclonal and the variation of sensitive response of the lines of somaclonal to sowing date. [Method]The RITSD changing of agronomic traits was studied by using 24 rice somaclonal and its donor parent under two sowing dates. [Result]The average values of RITSD were higher （over one） for the traits of pant height （PH）,density of spikelets （DS）,filled spikelets per panicle （FSP）,spikelets per panicle （SP） and grain weight per plant （GWP）,but lower for days of sowing to heading （DSH）,effective panicles （EP）,panicle length （PL）,seed setting rate （SS） and 1 000-grain weight （1 000-GW）. These showed that PH,DS,FSP,SP and GWP were easily affected by sowing date and tended to higher with the later sowing; the RITSD of somaclonal changed with the agronomic traits. The frequency of RITSD＇ variation of DSH and PH was higher than that of PL. The RITSD＇ value of EP,PL,DS,FSP,SP and SS became higher,and higher or lower for DSH and GWP in different somaclonal; compared with the donor,20 of 24 was significantly different,and the frequency of RITSD variation was over 83. 3%,however,RITSD of the most lines （75%） changed only for 1-2 characters; cluster analysis showed that the RITSD of agronomic traits belonged to different combinations of somaclonal in rice. [Conclusion]the study had provided a theoretical basis for the screening and using of the somaclonal.展开更多
In order to establish the relationship between the measured dynamic response and the health status of long-span bridges, a double-layer model updating method for steel-concrete composite beam cable-stayed bridges is p...In order to establish the relationship between the measured dynamic response and the health status of long-span bridges, a double-layer model updating method for steel-concrete composite beam cable-stayed bridges is proposed. Measured frequencies are selected as the first-layer reference data, and the mass of the bridge deck, the grid density, the modulus of concrete and the ballast on the side span are modified by using a manual tuning technique. Measured global positioning system （GPS） data is selected as the second-layer reference data, and the degradation of the integral structure stiffness EI of the whole bridge is taken into account for the second-layer model updating by using the finite element iteration algorithm. The Nanpu Bridge in Shanghai is taken as a case to verify the applicability of the proposed model updating method. After the first-layer model updating, the standard deviation of modal frequencies is smaller than 7%. After the second-layer model updating, the error of the deflection of the mid-span is smaller than 10%. The integral structure stiffness of the whole bridge decreases about 20%. The research results show a good agreement between the calculated response and the measured response.展开更多
It is acknowledged that teachers' instruction and guidance play an important role in students' improvements of schooling. A number of teachers, however, regard effectively responding to students' papers as...It is acknowledged that teachers' instruction and guidance play an important role in students' improvements of schooling. A number of teachers, however, regard effectively responding to students' papers as a touchy issue. In order to address this problem, this essay will review some of the major studies on teachers' response to students' writing in a historical way and, from these studies, some beneficial methods will be suggested, such as a process approach, collaborative ways of writing and motivational techniques.展开更多
Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% ...Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.展开更多
Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personali...Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.展开更多
This review aims to provide a concise overview of the trauma management evolution in the past decade. 1） Trauma care priorities have incorporated staff protection against infection and early decision making in additi...This review aims to provide a concise overview of the trauma management evolution in the past decade. 1） Trauma care priorities have incorporated staff protection against infection and early decision making in addition to the conventional ABCDE. 2） Five stratified levels for DAM have replaced the non-specific conventional Plans A ＆ B. 3） CT scanning can be the tunnel to death for the hemodynamically unstable patient. 4） DPL has virtually been replaced by the FAST USG. 5） Direct whole-body MDCT provides rapid imaging diagnosis ＆ expedites the definitive treatment but carries high radiation hazards. 6） The dynamic shock assessment by fluid resuscitation response provides more outcome-specific evaluation than the static blood volume loss model. 7） DCR comprising of permissive hypotension, hemostatic resuscitation ＆ DCS aims to overcome the lethal triad of trauma. Early transfusion of blood components of FFP ＆ platelet concentrates improves the outcome in massive blood transfusion. 8） DCS aims to rectify the deranged physiology and not to fully restore the damaged anatomy. 9） A pre-defined protocol for major pelvic fracture can be life-saving and the novel Pre-PPP （pre-peritoneal pelvic packing） may further reduce mortality coupled with the necessary TCAE. 10） Injury prevention is equally important if not more than the trauma resuscitation ＆ operation.展开更多
AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systemati...AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.展开更多
文摘IN March 2018, the United States slapped tariffs of 25 percent on steel imports and 10 percent on aluminum in the name of national security under Section 232 of the Trade Expansion Act of 1962. Then, the Office of the United States Trade Representative released a report on the investigation of China under Section 301 of the Trade Act of 1974, claiming China's acts, policies, and practices regarding technology transfer, intellectual property, and innovation are “unreasonable and discriminatory, and burden U.S. commerce.”
文摘1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Partial hepatectomy is recommended for patients with early stage HCC.[2]A large proportion of patients with HCC inChina are diagnosed in the intermediate to advanced HCC stages,rendering them ineligible for hepatectomy due to aspects such as liver dysfunction,insufficient residual liver volume,or surgical technique.
基金supported by National Key Research & Development Program of China (2022YFC3006201)。
文摘Emergency medical services (EMS) are a vital element of the public healthcare system in China,^([1])providing an opportunity to respond to critical medical conditions and save people’s lives.^([2])The accessibility of EMS has received considerable attention in health and transport geography studies.^([3])One of the optimal gauges for evaluating the accessibility of EMS is the response time,which is defined as the time from receiving an emergency call to the arrival of an ambulance.^([4])Beijing has already reduced the response time to approximately12 min,and the next goal is to ensure that the response time across Beijing does not exceed 12 min (the information comes from the Beijing Emergency Medical Center).
基金supported by China Postdoctoral Science Foundation(2022M723356),"From 0 to 1"Original Innovation Project of the Basic Frontier Scientific Research Program of the Chinese Academy of Sciences(29J20-015-Ⅲ)Chinese Academy of Sciences 100 Talents Project:Research on Task oriented Functional Brain Development of Infants(29J20-052-Ⅲ)Natural Science Basic Research Plan in Shaanxi Province of China(2022JQ544).
文摘Optogenetics,a technique that employs light for neuromodulation,has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type specificity.However,visible light,particularly blue and green light,commonly used in conventional optogenetics,has limited penetration in biological tissue.This limitation necessitates the implantation of optical fibers for light delivery,especially in deep brain regions,leading to tissue damage and experimental constraints.To overcome these challenges,the use of orange-red and infrared light with greater tissue penetration has emerged as a promising approach for tetherless optical neuromodulation.In this review,we provide an overview of the development and applications of tetherless optical neuromodulation methods with long wavelengths.We first discuss the exploration of orange-red wavelength-responsive rhodopsins and their performance in tetherless optical neuromodulation.Then,we summarize two novel tetherless neuromodulation methods using near-infrared light:upconversion nanoparticle-mediated optogenetics and photothermal neuromodulation.In addition,we discuss recent advances in mid-infrared optical neuromodulation.
文摘Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.
基金supported by the Taipei Tzu Chi Hospital through grants from the Buddhist Tzu Chi Medical Foundation under the Numbers TCRD-TPE-111-23(2/3)and TCRD-TPE-113-20,Taipei,Taiwan.
文摘Tazarotene-induced gene 1(TIG1)is induced by a derivative of vitamin A and is known to regulate many important biological processes and control the development of cancer.TIG1 is widely expressed in various tissues;yet in many cancer tissues,it is not expressed because of the methylation of its promoter.Additionally,the expression of TIG1 in cancer cells inhibits their growth and invasion,suggesting that TIG1 acts as a tumor suppressor gene.However,in some cancers,poor prognosis is associated with TIG1 expression,indicating its protumor growth characteristics,especially in promoting the invasion of inflammatory breast cancer cells.This review comprehensively summarizes the roles of the TIG1 gene in cancer development and details the mechanisms through which TIG1 regulates cancer development,with the aim of understanding its various roles in cancer development.
文摘The judicial application of digital evidence in criminal cases(criminal digital evidence)is an inevitable trend for the digital transformation of criminal proceedings in the macro context of the digital economy.It is characterized by digitization,diversification,and traceability.The application of criminal digital evidence can be divided into two main scenarios:the vertical scenario involving phases such as filing,prosecution,and trial;the horizontal scenario related to specific types of crimes.Criminal digital evidence is primarily applied to handling non-contact crimes,such as cybercrimes.However,the application of such evidence may infringe upon the basic rights of suspects,including their rights to privacy,rights to know,and rights to defense.Furthermore,the diversified and non-systematic nature of digital evidence may lead to challenges in applying the law,particularly with algorithmic“black boxes,”which can result in judicial discrimination and other drawbacks.Therefore,it is necessary to formulate or improve the regulatory framework for criminal digital evidence to ensure its lawful and standardized application.Additionally,judicial authorities must strengthen collaboration in case handling to ensure smooth coordination in collecting and applying digital evidence,thereby realizing its efficient litigation value.Furthermore,it is essential to check and balance the algorithm-based conviction and sentencing to protect the legitimate rights and interests of the parties involved,achieving high-quality human rights protection.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-C-005.
文摘BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.
基金Supported by Chongqing Major Research Project "Innovation in Hybrid Rice Breeding and New Materials" ( CSTC, 2007, AA1019 )Sichuan Province Breeding Research Project (06yzgg-01)~~
文摘[Objective]The aim was to study the sensitive response characteristics of the main agronomic traits of somaclonal and the variation of sensitive response of the lines of somaclonal to sowing date. [Method]The RITSD changing of agronomic traits was studied by using 24 rice somaclonal and its donor parent under two sowing dates. [Result]The average values of RITSD were higher （over one） for the traits of pant height （PH）,density of spikelets （DS）,filled spikelets per panicle （FSP）,spikelets per panicle （SP） and grain weight per plant （GWP）,but lower for days of sowing to heading （DSH）,effective panicles （EP）,panicle length （PL）,seed setting rate （SS） and 1 000-grain weight （1 000-GW）. These showed that PH,DS,FSP,SP and GWP were easily affected by sowing date and tended to higher with the later sowing; the RITSD of somaclonal changed with the agronomic traits. The frequency of RITSD＇ variation of DSH and PH was higher than that of PL. The RITSD＇ value of EP,PL,DS,FSP,SP and SS became higher,and higher or lower for DSH and GWP in different somaclonal; compared with the donor,20 of 24 was significantly different,and the frequency of RITSD variation was over 83. 3%,however,RITSD of the most lines （75%） changed only for 1-2 characters; cluster analysis showed that the RITSD of agronomic traits belonged to different combinations of somaclonal in rice. [Conclusion]the study had provided a theoretical basis for the screening and using of the somaclonal.
基金The Special Project of the Ministry of Construction ofChina (No.20060909).
文摘In order to establish the relationship between the measured dynamic response and the health status of long-span bridges, a double-layer model updating method for steel-concrete composite beam cable-stayed bridges is proposed. Measured frequencies are selected as the first-layer reference data, and the mass of the bridge deck, the grid density, the modulus of concrete and the ballast on the side span are modified by using a manual tuning technique. Measured global positioning system （GPS） data is selected as the second-layer reference data, and the degradation of the integral structure stiffness EI of the whole bridge is taken into account for the second-layer model updating by using the finite element iteration algorithm. The Nanpu Bridge in Shanghai is taken as a case to verify the applicability of the proposed model updating method. After the first-layer model updating, the standard deviation of modal frequencies is smaller than 7%. After the second-layer model updating, the error of the deflection of the mid-span is smaller than 10%. The integral structure stiffness of the whole bridge decreases about 20%. The research results show a good agreement between the calculated response and the measured response.
文摘It is acknowledged that teachers' instruction and guidance play an important role in students' improvements of schooling. A number of teachers, however, regard effectively responding to students' papers as a touchy issue. In order to address this problem, this essay will review some of the major studies on teachers' response to students' writing in a historical way and, from these studies, some beneficial methods will be suggested, such as a process approach, collaborative ways of writing and motivational techniques.
文摘Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.
基金Supported by Grants from Beijing Academic Leaders Program,NO.2009-2-17Beijing Natural Science Foundation,No.7102029+5 种基金Capital Medical Developed Research Fund,No.2007-1023New Scholar Star Program of Ministry of EducationNational Basic Research Program of China,No.2011CB504300Specialized Research Fund for the Doctoral Program of Higher Education,No.20130001110108National Natural Science Foundation for Distinguished Young Scholars,No.81301748Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No.IRT13003 and No.NIH/NCI U54 CA156735
文摘Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.
文摘This review aims to provide a concise overview of the trauma management evolution in the past decade. 1） Trauma care priorities have incorporated staff protection against infection and early decision making in addition to the conventional ABCDE. 2） Five stratified levels for DAM have replaced the non-specific conventional Plans A ＆ B. 3） CT scanning can be the tunnel to death for the hemodynamically unstable patient. 4） DPL has virtually been replaced by the FAST USG. 5） Direct whole-body MDCT provides rapid imaging diagnosis ＆ expedites the definitive treatment but carries high radiation hazards. 6） The dynamic shock assessment by fluid resuscitation response provides more outcome-specific evaluation than the static blood volume loss model. 7） DCR comprising of permissive hypotension, hemostatic resuscitation ＆ DCS aims to overcome the lethal triad of trauma. Early transfusion of blood components of FFP ＆ platelet concentrates improves the outcome in massive blood transfusion. 8） DCS aims to rectify the deranged physiology and not to fully restore the damaged anatomy. 9） A pre-defined protocol for major pelvic fracture can be life-saving and the novel Pre-PPP （pre-peritoneal pelvic packing） may further reduce mortality coupled with the necessary TCAE. 10） Injury prevention is equally important if not more than the trauma resuscitation ＆ operation.
文摘AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that the benefits of intraand cross-class switch do not significantly differ. Data on combination strategy are controversial regarding TCA-SSRI combination(positive results in old studies, negative in more recent study) and bupropion-SSRI combination(three open series studies but not three controlled trails support the useful of this combination) and positive regard mirtazapine(or its analogue mianserine) combination with ADs of different classes. As regards the augmentation strategy, available evidences supported the efficacy of TCA augmentation with lithium salts and thyroid hormone(T3), but are conflicting regard the SSRI augmentation with these two drugs(1 positive trial out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled studies showed the efficacy of AD augmentation with aripiprazole(5 positive trials out 5), quetiapine(3 positive trials out 3) and, at less extent, of fluoxetine augmentation with olanzapine(3 positive trials out 6), so these drugs received the FDA indication for the acute treatment of TRD. Results on AD augmentation with risperidone are conflicting(2 short term positive trials, 1 short-term and 1 long-term negative trials). Case series and open-label trials showed that AD augmentation with pramipexole or ropinirole, two dopamine agonists, could be an effective treatment for TRD(response rate to pramipexole 48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo-controlled study does not support the superiority of pramipexole over placebo. Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S-adenosil-Lmetionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD augmentation for TRD. Combining the available evidences with our experience we suggest treating non-responders to one SSRI bupropion or mirtazapine trial by switching to venlafaxine, and nonresponders to one venlafaxine trial by switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI or venlafaxine. In non-responders to two or more ADs(including at least one TCA if tolerated) current AD regimen could be augmented with lithium salts(mainly in patients with bipolar depression or suicidality), SGAs(mostly aripiprazole) or DA-agonists(mostly pramipexole). In patients with severe TRD, i.e., non-responders to combination and augmentation strategies as well as to electroconvulsive therapy if workable, we suggest to try a combination plus augmentation strategy.CONCLUSION: Our study identifies alternative effective treatment strategies for TRD. Further studies are needed to compare the efficacy of different strategies in more homogeneous subpopulations.
基金The Project Advanced Buildings technology in a Dense Urban Environment of Hong Kong Polytechnic University the Application Lab of Digital Seismic Wave Data in Center for Analysis and Prediction+1 种基金 China Seismological Bureau and the Earthquake Prediction
