Background Adequate data collection can enhance the realism of online rendering or offline playback of haptic surface textures.A parallel challenge is to reduce communication delays and improve storage space utilizati...Background Adequate data collection can enhance the realism of online rendering or offline playback of haptic surface textures.A parallel challenge is to reduce communication delays and improve storage space utilization.Methods Based on the similarity of the short-term amplitude spectrum trend,this study proposes a frequency-domain compression method.A compression framework is designed,which first maps the amplitude spectrum into grayscale images,compresses them with a still image compression method,and then adaptively encodes the maximum amplitude and part of the initial phase for each time window to achieve the final compression.Results The comparison between the original signal and the recovered signal shows that when the time-frequency similarity is 90%,the average compression ratio of our method is 9.85%in the case of a single interaction point.The subjective score for similarity was found to be high,with an average of 87.85.Conclusions Our method can be used for offline compression of vibrotactile data.For multi-interaction points in space,the trend similarity grayscale image can be reused,and the compression ratio is further reduced.展开更多
Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening ps...Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention.Here,the validity of distress thermometer(DT)in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed,and the prevalence of anxiety and depression was evaluated.Methods:We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study.Before the first cycle of adjuvant chemotherapy,the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale(HADS).In total,191 valid cases were analyzed.HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points.Results:The definitive prevalence of both anxiety and depression was 8.90%.The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85,respectively,both of which were significantly higher than corresponding Chinese norms(P<0.01).The areas under receiver operating characteristic curves of DT for the diagnoses of FCs'anxiety and depression were 0.904 and 0.885,respectively.A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression.Conclusions:The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm.DT might be an effective tool to initially screen psychological distress among FCs.This process could be integrated into the palliative care of breast cancer patients and warrant further research.展开更多
背景与目的越来越多的癌症患者死于心血管疾病。三阴性乳腺癌(triple-negative breast cancer,TNBC)可选的治疗方法有限,因此化疗引起的心脏毒性对该类患者非常重要。心脏自噬是心脏毒性的重要机制之一。本研究旨在研究化疗对TNBC患者...背景与目的越来越多的癌症患者死于心血管疾病。三阴性乳腺癌(triple-negative breast cancer,TNBC)可选的治疗方法有限,因此化疗引起的心脏毒性对该类患者非常重要。心脏自噬是心脏毒性的重要机制之一。本研究旨在研究化疗对TNBC患者的心脏毒性,筛选易感人群,探讨心脏毒性与自噬相关基因多态性的相关性。方法在2450例I–III期TNBC患者中,有147例纳入了本研究。大多数患者在化疗周期前进行心电图(electrocardiography,ECG)检查,并根据临床需要进行超声心动图(echocardiography,UCG)检查。所有ECG和UCG资料均由阜外医院国家心血管病中心的心血管专家重新评判。根据美国国家生物技术信息中心数据库和癌症体细胞突变目录数据库,我们筛选了25个与自噬相关的单核苷酸多态性(single nucleotide polymorphisms,SNPs),并对147例TNBC患者进行了基因分型。采用配对样本T检验、卡方检验和logistic回归模型进行分析。结果每个化疗周期后,只有46(31.3%)例患者的ECG完全正常。在接受UCG的16例患者中,有2(12.5%)例患者左心室射血分数可逆性下降。使用蒽环类药物和过量饮酒是ECG异常的危险因素。随着化疗的持续,心率逐渐增加。蒽环类药物与QRS期持续异常有关(P=0.043)。我们对25个与自噬有关的SNP进行基因分型后发现,自噬相关基因13(ATG13)rs10838611的G等位基因与ECG异常显著相关(优势比=2.258,95%置信区间:1.318–3.869;P=0.003)。结论化疗引起的ECG异常在真实世界中很常见。自噬相关单核苷酸多态性与化疗引起的心脏毒性相关,本研究为自噬是化疗所致心脏损害的原因提供了新的证据。展开更多
In this paper,we focus on the problem of joint estimation of DOA,power and polarization angle from sparse reconstruction perspective with array gain-phase errors,where a partly calibrated cocentered orthogonal loop an...In this paper,we focus on the problem of joint estimation of DOA,power and polarization angle from sparse reconstruction perspective with array gain-phase errors,where a partly calibrated cocentered orthogonal loop and dipole(COLD)array is utilized.In detailed implementations,we first combine the output of loop and dipole in second-order statistics domain to receive the source signals completely,and then we use continuous multiplication operator to achieve gain-phase errors calibration.After compensating the gain-phase errors,we construct a log-penalty-based optimization problem to approximate`0 norm and further exploit difference of convex(DC)functions decomposition to achieve DOA.With the aid of the estimated DOAs,the power and polarization angle estimation are obtained by the least squares(LS)method.By conducting numerical simulations,we show the effectiveness and superiorities of the proposed method.展开更多
Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the a...Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.展开更多
This paper takes advantage of the depth camera of somatosensory kinect and sensors to implement gesture recognition and design a virtual instrument system. As long as the user waves his arm without the help of other e...This paper takes advantage of the depth camera of somatosensory kinect and sensors to implement gesture recognition and design a virtual instrument system. As long as the user waves his arm without the help of other equipments, our system can automatically recognize the hand gesture and make suitable sound. In order to achieve depth camera's detection of hands movement,this paper introduce the depth imaging technology Light Coding and bone tracking technology to obtain the actual position information and hand movement information of the human body. Feet movement detection uses sensor technology, different stampede strength outputs different digital number after AD conversion so that the intensity can be controlled. A series of experiments show that the system has good fluency and practicality and increased the fun of playing instruments.展开更多
Background Ultrasonic tactile representation utilizes focused ultrasound to create tactile sensations on the bare skin of a user's hand that is not in contact with a device.This study is a preliminary investigatio...Background Ultrasonic tactile representation utilizes focused ultrasound to create tactile sensations on the bare skin of a user's hand that is not in contact with a device.This study is a preliminary investigation on whether different ultrasonic haptic rendering methods have an impact on the perceptual threshold.Methods This study conducted experiments with the adaptive step method to obtain participants'perceptual thresholds.We examine(1)whether different parts on the palm of the hand have different perceptual thresholds;(2)whether the perceptual threshold is different when the ultrasonic focus point is stationary and when it moves in different trajectories;(3)whether different moving speeds of the ultrasonic focus point have an influence on the perceptual threshold;and(4)whether the addition of a DC offset to the modulating wave has an impact on the perceptual threshold.Results The results show that the center of the palm is more sensitive to ultrasonic haptics than the fingertip;compared with a fast-moving focus point,the palm is more sensitive to a stationary and slow-moving focus point.When the modulating wave has a DC offset,the palm is sensitive to a much smaller modulation amplitude.Conclusion For the future ultrasonic tactile representation systems,dynamic adjustment of intensity is required to compensate the difference in perceptual thresholds under different rendering methods to achieve more realistic ultrasonic haptics.展开更多
Background:Vaccination has been shown effective in controlling the global coronavirus disease 2019(COVID-19)pandemic and reducing severe cases.This study was to assess the flare and change in disease activity after CO...Background:Vaccination has been shown effective in controlling the global coronavirus disease 2019(COVID-19)pandemic and reducing severe cases.This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis(RA).Methods:A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status.Each of them was examined every 3 to 6 months.In the vaccination group,disease activity was compared before and after vaccination.The rates of flare defined as disease activity scores based on 28-joint count(DAS28)>3.2 withΔDAS28≥0.6 were compared between vaccination and non-vaccination groups.Results:A total of 202 eligible RA patients were enrolled.Of these,98 patients received no vaccine shot(non-vaccination group),and 104 patients received two doses of vaccine(vaccination group).The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days,respectively.The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar.At enrollment,gender,RA disease course,seropositivity,and disease activity were comparable across the two groups.Flare was observed in five(4.8%)of the vaccination group patients and nine(9.2%)of the non-vaccination group patients at post-vaccination assessment(P=0.221).In terms of safety,29(27.9%)patients experienced adverse events(AEs)after vaccination.No serious AEs occurred.Conclusions:COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity.Patients with stable RA should be encouraged to receive the COVID-19 vaccination.展开更多
Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been ...Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast cancer.Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical practice.This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.Methods:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood samples.Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.Results:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomogram was constructed based on the criteria and significant clinicopatho-logical characteristics with a C-index of 0.613(P=0.010).Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer.展开更多
Genetic gain-of-function mutations of warm temperature-sensitive transient receptor potential vanilloid 3(TRPV3)channel cause Olmsted syndrome characterized by severe itching and keratoderma,indicating that pharmacolo...Genetic gain-of-function mutations of warm temperature-sensitive transient receptor potential vanilloid 3(TRPV3)channel cause Olmsted syndrome characterized by severe itching and keratoderma,indicating that pharmacological inhibition of TRPV3 may hold promise for therapy of chronic pruritus and skin diseases.However,currently available TRPV3 tool inhibitors are either nonselective or less potent,thus impeding the validation of TRPV3 as therapeutic target.Using whole-cell patch-clamp and single-channel recordings,we report the identification of two natural dicaffeoylquinic acid isomers isochlorogenic acid A(IAA)and isochlorogenic acid B(IAB)that selectively inhibit TRPV3 currents with IC50 values of 2.7±1.3 and 0.9±0.3μmol/L,respectively,and reduce the channel open probability to 3.7±1.2%and 3.2±1.1%from 26.9±5.5%,respectively.In vivo evaluation confirms that both IAA and IAB significantly reverse the ear swelling of dermatitis and chronic pruritus.Furthermore,the isomer IAB is able to rescue the keratinocyte death induced by TRPV3 agonist carvacrol.Molecular docking combined with site-directed mutations reveals two residues T636 and F666 critical for the binding of the two isomers.Taken together,our identification of isochlorogenic acids A and B that act as specific TRPV3 channel inhibitors and gating modifiers not only provides an essential pharmacological tool for further investigation of the channel pharmacology and pathology,but also holds developmental potential for treatment of dermatitis and chronic pruritus.展开更多
Background:An increasing number of cancer patients die of cardiovascular diseases.The cardiotoxicity of chemo-therapy is particularly important in triple-negative breast cancer(TNBC)with limited therapeutic options.Ca...Background:An increasing number of cancer patients die of cardiovascular diseases.The cardiotoxicity of chemo-therapy is particularly important in triple-negative breast cancer(TNBC)with limited therapeutic options.Cardiac autophagy is an important mechanism of cardiotoxicity.This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC,screen the susceptible population,and determine the relationship between cardiotoxicity and autophagy-related polymorphisms.Methods:From a total of 2450 stage I-III TNBC patients,147 met the inclusion criteria and finally recruited.Electro-cardiography(ECG)was performed before most chemotherapy cycles,and echocardiography(UCG)was performed according to clinical needs.All ECG and UCG records were re-interpreted by cardiologists at the National Center for Cardiovascular Disease,Fuwai Hospital.According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database,we selected 25 single nucleotide polymorphisms(SNPs)related to autophagy and genotyped the 147 TNBC patients.Paired-sample T tests,Chi squared tests,and logistic regression models were employed for the analysis.Results:Only 46(31.3%)patients had normal ECG records after every chemotherapy cycle.Among the 16 patients who underwent UCG,2(12.5%)had a reversible decrease of left ventricular ejection fraction.The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities.With the continuation of chemotherapy,heart rate gradually increased.Anthracyclines were associated with QRS duration abnormalities(P=0.043).After genotyping for 25 autophagy-related SNPs,we found that the G allele of autophagy-related 13(ATG13)rs10838611 was significantly associated with ECG abnormalities(odds ratio=2.258,95%confidence interval=1.318-3.869;P=0.003).Conclusion:ECG abnormalities caused by chemotherapy are common in the real world.Autophagy-related SNPs are associated with chemotherapy-induced cardiotoxicity,thereby providing new evidence for autophagy as a cause of chemotherapy-induced cardiac damage.展开更多
Main observation and conclusion The stability of nanosized platinum catalyst in direct propane dehydrogenation reaction is one of most critical challenges,which hin-ders the further improvements of catalytic performan...Main observation and conclusion The stability of nanosized platinum catalyst in direct propane dehydrogenation reaction is one of most critical challenges,which hin-ders the further improvements of catalytic performance.The cokes from side reaction covering the active site seriously undermine the catalyst stability.In this work,first principles calculations are performed to explore the catalytic properties of supported subna-nometer platinum cluster on carbon nanotube support and focus is put on the inhibition of deep dehydrogenation.The reactivities of metal,interface,and tin promoter are investigated at the same footing.The whole reaction pathway from propane adsorption to propene desorption is revealed for different sites.It turns out that the C-H bond activation in propane is not the catalytic step with the largest barrier.Instead,the desorption of propene is more difficult.The comparison between different sites indicates that the in-terface between metal and support and Sn promoter is helpful to curb the propene deep dehydrogenation.Moreover,a descriptor is proposed to screen the potential effective propane direct dehydrogenation catalyst.The current work provides important insights on the development of new dehydrogenation catalyst.展开更多
基金Supported by the Natural Science Foundation of China(61631010)。
文摘Background Adequate data collection can enhance the realism of online rendering or offline playback of haptic surface textures.A parallel challenge is to reduce communication delays and improve storage space utilization.Methods Based on the similarity of the short-term amplitude spectrum trend,this study proposes a frequency-domain compression method.A compression framework is designed,which first maps the amplitude spectrum into grayscale images,compresses them with a still image compression method,and then adaptively encodes the maximum amplitude and part of the initial phase for each time window to achieve the final compression.Results The comparison between the original signal and the recovered signal shows that when the time-frequency similarity is 90%,the average compression ratio of our method is 9.85%in the case of a single interaction point.The subjective score for similarity was found to be high,with an average of 87.85.Conclusions Our method can be used for offline compression of vibrotactile data.For multi-interaction points in space,the trend similarity grayscale image can be reused,and the compression ratio is further reduced.
基金supported by the National Science Foundation of China(91545117)the Natural Science Foundation of Liaoning Province(201602676)+1 种基金the Fundamental Research Funds for Colleges and Universities in Liaoning Province(LQN201703)the Startup Foundation for Doctors of Shenyang Normal University(BS201620)~~
文摘Objective:Family caregivers(FCs)of breast cancer patients play a vital role throughout the treatment process.Psychological distress of FCs is common and often ignored.A simple and effective instrument for screening psychological distress would help in selecting those FCs requiring special attention and intervention.Here,the validity of distress thermometer(DT)in FCs of Chinese breast cancer patients receiving postoperative chemotherapy was assessed,and the prevalence of anxiety and depression was evaluated.Methods:We recruited 200 FCs of hospitalized breast cancer patients in this cross-sectional descriptive study.Before the first cycle of adjuvant chemotherapy,the levels of anxiety and depression among FCs were assessed using DT and Hospital Anxiety and Depression Scale(HADS).In total,191 valid cases were analyzed.HADS was used as the diagnostic standard to assess the effectiveness of DT as a screening tool for anxiety and depression as well as to analyze the diagnostic efficiency of DT at various cutoff points.Results:The definitive prevalence of both anxiety and depression was 8.90%.The mean level of anxiety and depression among FCs was 5.64±3.69 and 5.09±3.85,respectively,both of which were significantly higher than corresponding Chinese norms(P<0.01).The areas under receiver operating characteristic curves of DT for the diagnoses of FCs'anxiety and depression were 0.904 and 0.885,respectively.A cutoff value of 5 produced the best diagnostic effects of DT for anxiety and depression.Conclusions:The levels of both anxiety and depression were higher in the FCs of Chinese breast cancer patients receiving postoperative chemotherapy than the national norm.DT might be an effective tool to initially screen psychological distress among FCs.This process could be integrated into the palliative care of breast cancer patients and warrant further research.
文摘背景与目的越来越多的癌症患者死于心血管疾病。三阴性乳腺癌(triple-negative breast cancer,TNBC)可选的治疗方法有限,因此化疗引起的心脏毒性对该类患者非常重要。心脏自噬是心脏毒性的重要机制之一。本研究旨在研究化疗对TNBC患者的心脏毒性,筛选易感人群,探讨心脏毒性与自噬相关基因多态性的相关性。方法在2450例I–III期TNBC患者中,有147例纳入了本研究。大多数患者在化疗周期前进行心电图(electrocardiography,ECG)检查,并根据临床需要进行超声心动图(echocardiography,UCG)检查。所有ECG和UCG资料均由阜外医院国家心血管病中心的心血管专家重新评判。根据美国国家生物技术信息中心数据库和癌症体细胞突变目录数据库,我们筛选了25个与自噬相关的单核苷酸多态性(single nucleotide polymorphisms,SNPs),并对147例TNBC患者进行了基因分型。采用配对样本T检验、卡方检验和logistic回归模型进行分析。结果每个化疗周期后,只有46(31.3%)例患者的ECG完全正常。在接受UCG的16例患者中,有2(12.5%)例患者左心室射血分数可逆性下降。使用蒽环类药物和过量饮酒是ECG异常的危险因素。随着化疗的持续,心率逐渐增加。蒽环类药物与QRS期持续异常有关(P=0.043)。我们对25个与自噬有关的SNP进行基因分型后发现,自噬相关基因13(ATG13)rs10838611的G等位基因与ECG异常显著相关(优势比=2.258,95%置信区间:1.318–3.869;P=0.003)。结论化疗引起的ECG异常在真实世界中很常见。自噬相关单核苷酸多态性与化疗引起的心脏毒性相关,本研究为自噬是化疗所致心脏损害的原因提供了新的证据。
基金the National Natural Science Foundation of China under Grant 61171137.
文摘In this paper,we focus on the problem of joint estimation of DOA,power and polarization angle from sparse reconstruction perspective with array gain-phase errors,where a partly calibrated cocentered orthogonal loop and dipole(COLD)array is utilized.In detailed implementations,we first combine the output of loop and dipole in second-order statistics domain to receive the source signals completely,and then we use continuous multiplication operator to achieve gain-phase errors calibration.After compensating the gain-phase errors,we construct a log-penalty-based optimization problem to approximate`0 norm and further exploit difference of convex(DC)functions decomposition to achieve DOA.With the aid of the estimated DOAs,the power and polarization angle estimation are obtained by the least squares(LS)method.By conducting numerical simulations,we show the effectiveness and superiorities of the proposed method.
基金supported by grant from the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021I2M-1-014)。
文摘Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.
文摘This paper takes advantage of the depth camera of somatosensory kinect and sensors to implement gesture recognition and design a virtual instrument system. As long as the user waves his arm without the help of other equipments, our system can automatically recognize the hand gesture and make suitable sound. In order to achieve depth camera's detection of hands movement,this paper introduce the depth imaging technology Light Coding and bone tracking technology to obtain the actual position information and hand movement information of the human body. Feet movement detection uses sensor technology, different stampede strength outputs different digital number after AD conversion so that the intensity can be controlled. A series of experiments show that the system has good fluency and practicality and increased the fun of playing instruments.
基金the National Key Research and Development Program(2016YFB1001304)and the National Natural Science Foundation of China(61631010).
文摘Background Ultrasonic tactile representation utilizes focused ultrasound to create tactile sensations on the bare skin of a user's hand that is not in contact with a device.This study is a preliminary investigation on whether different ultrasonic haptic rendering methods have an impact on the perceptual threshold.Methods This study conducted experiments with the adaptive step method to obtain participants'perceptual thresholds.We examine(1)whether different parts on the palm of the hand have different perceptual thresholds;(2)whether the perceptual threshold is different when the ultrasonic focus point is stationary and when it moves in different trajectories;(3)whether different moving speeds of the ultrasonic focus point have an influence on the perceptual threshold;and(4)whether the addition of a DC offset to the modulating wave has an impact on the perceptual threshold.Results The results show that the center of the palm is more sensitive to ultrasonic haptics than the fingertip;compared with a fast-moving focus point,the palm is more sensitive to a stationary and slow-moving focus point.When the modulating wave has a DC offset,the palm is sensitive to a much smaller modulation amplitude.Conclusion For the future ultrasonic tactile representation systems,dynamic adjustment of intensity is required to compensate the difference in perceptual thresholds under different rendering methods to achieve more realistic ultrasonic haptics.
基金supported by grants from the National Natural Science Foundation of China(Nos.81771740,81901646)Interdisciplinary Clinical Research Project of Peking University First Hospital(No.2021CR30)Peking University Medicine Seed Fund for Interdisciplinary Research supported by the Fundamental Research Funds for the Central Universities(No.BMU2022MX003)
文摘Background:Vaccination has been shown effective in controlling the global coronavirus disease 2019(COVID-19)pandemic and reducing severe cases.This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis(RA).Methods:A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status.Each of them was examined every 3 to 6 months.In the vaccination group,disease activity was compared before and after vaccination.The rates of flare defined as disease activity scores based on 28-joint count(DAS28)>3.2 withΔDAS28≥0.6 were compared between vaccination and non-vaccination groups.Results:A total of 202 eligible RA patients were enrolled.Of these,98 patients received no vaccine shot(non-vaccination group),and 104 patients received two doses of vaccine(vaccination group).The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days,respectively.The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar.At enrollment,gender,RA disease course,seropositivity,and disease activity were comparable across the two groups.Flare was observed in five(4.8%)of the vaccination group patients and nine(9.2%)of the non-vaccination group patients at post-vaccination assessment(P=0.221).In terms of safety,29(27.9%)patients experienced adverse events(AEs)after vaccination.No serious AEs occurred.Conclusions:COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity.Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
基金This study was funded by the National Natural Science Foundation of China(81472453)National High Technology Research and Development Program of China(2015AA020408)+3 种基金the Major Project of Beijing Municipal Science and Technology Commission(D161100000816004)the CAMS Initiative for Innovative Medicine(CAMS-12M-1-010,2017-I2M-3-004)PUMC Innovation Fund for Graduates(2018-1002-02-24)We thank all the physicians and nurses involved in the study for their contributions.
文摘Background:Epithelial-mesenchymal transition(EMT)is implicated in the metastatic process and presents a chal-lenge to epithelial cell adhesion molecule-based detection of circulating tumor cells(CTCs),which have been demon-strated to be a prognostic indicator in metastatic breast cancer.Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression,no standard recommendations have been established for clinical practice.This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients.Methods:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes(including epithelial CTCs,biphenotypic epithelial/mesenchymal CTCs,and mesenchymal CTCs)in peripheral blood samples.Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival(PFS)rate were conducted to determine the optimal cut-off values,and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination.Results:For predicting the 1-year PFS rate,the optimal cut-off value of total CTC count was 9.5(Area under the curve[AUC]=0.538,95%confidence interval[CI]=0.418-0.657),and that of the proportion of mesenchymal CTCs was 10.7%(AUC=0.581,95%CI=0.463-0.699).We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%.Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria(6.2 vs.9.9 months,P=0.010).A nomogram was constructed based on the criteria and significant clinicopatho-logical characteristics with a C-index of 0.613(P=0.010).Conclusions: The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer.
基金supported by National Natural Science Foundation of China(81903734,81973299 and 81573410)the Ministry of Science and Technology of the People’s Republic of China(2018ZX09711001-004-006)。
文摘Genetic gain-of-function mutations of warm temperature-sensitive transient receptor potential vanilloid 3(TRPV3)channel cause Olmsted syndrome characterized by severe itching and keratoderma,indicating that pharmacological inhibition of TRPV3 may hold promise for therapy of chronic pruritus and skin diseases.However,currently available TRPV3 tool inhibitors are either nonselective or less potent,thus impeding the validation of TRPV3 as therapeutic target.Using whole-cell patch-clamp and single-channel recordings,we report the identification of two natural dicaffeoylquinic acid isomers isochlorogenic acid A(IAA)and isochlorogenic acid B(IAB)that selectively inhibit TRPV3 currents with IC50 values of 2.7±1.3 and 0.9±0.3μmol/L,respectively,and reduce the channel open probability to 3.7±1.2%and 3.2±1.1%from 26.9±5.5%,respectively.In vivo evaluation confirms that both IAA and IAB significantly reverse the ear swelling of dermatitis and chronic pruritus.Furthermore,the isomer IAB is able to rescue the keratinocyte death induced by TRPV3 agonist carvacrol.Molecular docking combined with site-directed mutations reveals two residues T636 and F666 critical for the binding of the two isomers.Taken together,our identification of isochlorogenic acids A and B that act as specific TRPV3 channel inhibitors and gating modifiers not only provides an essential pharmacological tool for further investigation of the channel pharmacology and pathology,but also holds developmental potential for treatment of dermatitis and chronic pruritus.
基金The National Natural Sciences Foundation of China(Grant No.81573410)the Ministry of Science and Technology of China(Grant No.2014ZX09507003-006-004)the Natural Sciences Foundation of Shandong Province(Grant No.ZR2015QL008)
基金supported by the National Natural Science Foundation of China(No.81472453).
文摘Background:An increasing number of cancer patients die of cardiovascular diseases.The cardiotoxicity of chemo-therapy is particularly important in triple-negative breast cancer(TNBC)with limited therapeutic options.Cardiac autophagy is an important mechanism of cardiotoxicity.This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC,screen the susceptible population,and determine the relationship between cardiotoxicity and autophagy-related polymorphisms.Methods:From a total of 2450 stage I-III TNBC patients,147 met the inclusion criteria and finally recruited.Electro-cardiography(ECG)was performed before most chemotherapy cycles,and echocardiography(UCG)was performed according to clinical needs.All ECG and UCG records were re-interpreted by cardiologists at the National Center for Cardiovascular Disease,Fuwai Hospital.According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database,we selected 25 single nucleotide polymorphisms(SNPs)related to autophagy and genotyped the 147 TNBC patients.Paired-sample T tests,Chi squared tests,and logistic regression models were employed for the analysis.Results:Only 46(31.3%)patients had normal ECG records after every chemotherapy cycle.Among the 16 patients who underwent UCG,2(12.5%)had a reversible decrease of left ventricular ejection fraction.The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities.With the continuation of chemotherapy,heart rate gradually increased.Anthracyclines were associated with QRS duration abnormalities(P=0.043).After genotyping for 25 autophagy-related SNPs,we found that the G allele of autophagy-related 13(ATG13)rs10838611 was significantly associated with ECG abnormalities(odds ratio=2.258,95%confidence interval=1.318-3.869;P=0.003).Conclusion:ECG abnormalities caused by chemotherapy are common in the real world.Autophagy-related SNPs are associated with chemotherapy-induced cardiotoxicity,thereby providing new evidence for autophagy as a cause of chemotherapy-induced cardiac damage.
基金the National Natural Science Foun-dation of China(No.91845201)the Liaoning Natural Science Foundation(No.2019-ZD-0908).
文摘Main observation and conclusion The stability of nanosized platinum catalyst in direct propane dehydrogenation reaction is one of most critical challenges,which hin-ders the further improvements of catalytic performance.The cokes from side reaction covering the active site seriously undermine the catalyst stability.In this work,first principles calculations are performed to explore the catalytic properties of supported subna-nometer platinum cluster on carbon nanotube support and focus is put on the inhibition of deep dehydrogenation.The reactivities of metal,interface,and tin promoter are investigated at the same footing.The whole reaction pathway from propane adsorption to propene desorption is revealed for different sites.It turns out that the C-H bond activation in propane is not the catalytic step with the largest barrier.Instead,the desorption of propene is more difficult.The comparison between different sites indicates that the in-terface between metal and support and Sn promoter is helpful to curb the propene deep dehydrogenation.Moreover,a descriptor is proposed to screen the potential effective propane direct dehydrogenation catalyst.The current work provides important insights on the development of new dehydrogenation catalyst.
