The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bioni...The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.展开更多
This study describes the development of a cervical traction therapy simulation model that evaluates two types of the traction positions, namely the sitting position and the inclined position. An anatomically correct h...This study describes the development of a cervical traction therapy simulation model that evaluates two types of the traction positions, namely the sitting position and the inclined position. An anatomically correct human skeleton model and two mechanical traction device models were constructed in simulations using a physics engine. The anterior and posterior intervertebral separations were measured at both positions with a series of traction forces (60N to 200N) and traction angles (10°? to 40°?). The result suggested that the sitting position caused the subject to lean forward and as a result led to excessive anterior compression when traction angle is over 20 degrees. The inclined position creates greater intervertebral separations on both the anterior and posterior sides than the sitting position. This suggests that the inclined position may be more effective in increasing intervertebral separation than the sitting position.展开更多
This paper develops a generalized dynamical model to describe the interactive dynamics between normal cells, tumor cells, immune cells, drug therapy, electromagnetic field of the human cells, extracellular heat and fl...This paper develops a generalized dynamical model to describe the interactive dynamics between normal cells, tumor cells, immune cells, drug therapy, electromagnetic field of the human cells, extracellular heat and fluid transfer, and intercellular fractional mass of Oxygen, cell acidity and Pancreatin enzyme. The overall dynamics stability, controllability and observability have been investigated. Moreover, Cesium therapy is considered as a control input to the 11-dimensional dynamics using state-feedback controlled system and pole placement technique. This approach is found to be effective in driving the desired rate of tumor cell kill and converging the system to healthy equilibrium state. Furthermore, the ranges of the system dynamics parameters which lead to instability and growth of tumor cells have been identified. Finally, simulation results are demonstrated to verify the effectiveness of the applied approach which can be implemented successfully to cancer patients.展开更多
Purpose: We performed both, dosimetric and positional accuracy verification of dynamic tumor tracking (DTT) intensity modulated radiation therapy (IMRT), with the Vero4DRT system using a moving phantom (QUASAR respira...Purpose: We performed both, dosimetric and positional accuracy verification of dynamic tumor tracking (DTT) intensity modulated radiation therapy (IMRT), with the Vero4DRT system using a moving phantom (QUASAR respiratory motion platform;QUASAR phantom) and system log files. Methods: The QUASAR phantom was placed on a treatment couch. Measurement of the point dose and dose distribution was performed for conventional IMRT, with the QUASAR phantom static and moving;for DTT IMRT, this was performed with the phantom moving for pyramid shaped, prostate, paranasal sinus, and pancreas targets. The QUASAR phantom was driven by a sinusoidal signal in the superior-inferior direction. Furthermore, predicted positional errors induced by the Vero4DRT system and mechanical positional errors of the gimbal head, were calculated using the system log files. Results and Conclusion: For DTT IMRT, the dose at the evaluation point was within 3% compared with the verification plan, and the dose distribution in the passing rates of γ was 97.9%, with the criteria of 3% dose and 3 mm distance to agreement. The position error calculated from the log files was within 2 mm, suggesting the feasibility of employing DTT IMRT with high accuracy using the Vero4DRT system.展开更多
This work was undertaken to see how Ru II complexes can be suitable for photodynamic therapy through theoretical prediction. For that, four Ru II complexes, α-RuCl<sub>2</sub>(Azpy)<sub>2</sub>...This work was undertaken to see how Ru II complexes can be suitable for photodynamic therapy through theoretical prediction. For that, four Ru II complexes, α-RuCl<sub>2</sub>(Azpy)<sub>2</sub>, , and were used in unrestricted state by providing with no more energy than 2.68 eV. The unrestricted state allows the complex molecule to display each of its electrons in one orbital. All the calculations such as optimization, frequency and TD-DFT calculations were performed at WB97XD/Lanl2dz level. It resulted from this investigation that Ru II complexes are active for both mechanisms suitable for photodynamic therapy in presence or absence of <sup>3</sup>O<sub>2</sub>. Moreover, this reaction was assumed to take place only with Guanine DNA base as demonstrated in literature. Therefore, Guanine is admitted as the base most reacting with ruthenium complexes for photodynamic therapy. This work confirms our prediction regarding metallic complexes that are assumed to be photosensitized in condition that an electron must be isolated to favor the excitation. Nevertheless, Ru II complexes are found suitable for superficial therapy while Ru III must be active for deep therapy.展开更多
Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disorders including focal ische...Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disorders including focal ischemic stroke, a leading cause of brain injury and human death. One of the prominent pathological features of focal ischemic stroke is reactive astrogliosis and glial scar formation associated with morphological changes and proliferation. This review paper discusses the recent advances in spatial and temporal dynamics of morphology and proliferation of reactive astrocytes after ischemic stroke based on results from experimental animal studies. As reactive astrocytes exhibit stem cell-like properties, knowledge of dynamics of reactive astrocytes and glial scar formation will provide important insiehts for astrocvte-based cell therapy in stroke.展开更多
The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simples...The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simplest-level electron nuclear dynamics(SLEND)method.SLEND describes nuclei via classical mechanics and electrons with a singledeterminantal Thouless wavefunction.The 3402 SLEND conducted simulations from 42 independent CO2 target orientations provide a full description of all the reactive processes and their mechanisms in this system:non-charge-transfer scattering(NCTS),charge-transfer scattering(CTS),and single C=O bond dissociation;all this valuable information about reactivity is not accessible experimentally.Numerous details of the projectile scattering patterns are provided,including the appearance and coalescence of primary and secondary rainbow angles as a function of the target orientation.SLEND NCTS and CTS differential cross sections(DCSs)are evaluated in conjunction with advanced semi-classical techniques.SLEND NCTS DCS agrees well with its experimental counterpart at all the measured scattering angles,whereas SLEND CTS DCS agrees well at high scattering angles but less satisfactorily at lower ones.Remarkably,both NCTS and CTS SLEND DCSs predict the primary rainbow angle signatures in agreement with the experiment.展开更多
This study aims to validate the accuracy of a cervical traction therapy simulation model by comparing the intervertebral separations of six asymptomatic male adults when traction was applied to their cervical spines. ...This study aims to validate the accuracy of a cervical traction therapy simulation model by comparing the intervertebral separations of six asymptomatic male adults when traction was applied to their cervical spines. The subjects were tested on two mechanical traction devices, representing the inclined and sitting positions. A total of 55 radiographic images of their cervical spines were taken before and during traction. The result showed statistically significant intervertebral space changes in the inclined position but the changes in the sitting position were not statistically significant. The observed changes of the cervical spine were used to adjust parameters of the traction therapy model, which contains a human model with cervical spine built with springs and dampers and two traction devices in inclined and sitting positions. A series of traction forces and traction angles were applied to the model to simulate the actual parameters used in the experiment and the new model was used to evaluate the two traction positions. The result suggested that inclined position creates greater intervertebral separations on the posterior sides. Differences in separations due to age were not observed in both positions. The result also suggested that the inclined position provides better control in positioning the separations at different spinal segments than the sitting position.展开更多
This paper uses a molecular dynamics (MD) method for intensity-modulated proton therapy treatment planning optimization to overcome the problem of gradient-based optimization methods such as quasi-Newton, which is sen...This paper uses a molecular dynamics (MD) method for intensity-modulated proton therapy treatment planning optimization to overcome the problem of gradient-based optimization methods such as quasi-Newton, which is sensitive to starting conditions and is easily trapped in local minima. We implemented a molecular dynamics (MD) method and a quasi-Newton method for plan optimization. Three types of cancer cases, prostate, head-and-neck and lung cancer, were tested with three starting different initial conditions. Overall, the MD method consistently resulted in solutions with lower objective function values (OFVs) compared to those from the quasi-Newton algorithm. Furthermore, the MD method converged on the same OFV regardless of its initial starting points used for the prostate cancer case.展开更多
This paper is concerned with Hepato-Cellular Carcinoma (HCC) patients treated naturopathic agents. Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents. The great effect...This paper is concerned with Hepato-Cellular Carcinoma (HCC) patients treated naturopathic agents. Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents. The great effect is seen in patients treated with at least 4 agents that include Cordyceps sinensis. This greater certainty of patient survival without toxic side effects is significant benefit comparing with the conventional therapy. Treatment of HCC with a regimen of ≥4 agents prepared from natural products is associated with greater certainty of patient survival in a substantial portion of patients. The information dynamic model for certainty of patient survival is derived based on fluid mechanics, where a series of approximate solutions of the flow between two parallel flat walls, one of which is at rest, the other is suddenly accelerated from the rest to a constant velocity are used. The kinetic energy of certainty of patient survival decreases with increasing time, while the potential energy increases with increasing time. Total mechanical energy of patients treated with 4 or more agents is smaller than that treated with 3 or fewer agents. The kinetic energy (potential energy) of patients treated with 4 or more agents decreases (increases) more slower than the kinetic energy (potential energy) of patients treated with 3 or fewer agents.展开更多
Most patients with multiple myeloma (MM) respond well to initial therapy, but invariably relapse due to evolution of resistant phenotypes. Here we examine the evolutionary dynamics of proliferation of resistant MM phe...Most patients with multiple myeloma (MM) respond well to initial therapy, but invariably relapse due to evolution of resistant phenotypes. Here we examine the evolutionary dynamics of proliferation of resistant MM phenotypes during therapy. By applying computational models to data from three clinical trials for newly diagnosed MM patients, we have quantified the size and level of chemoresistance of subpopulations within the tumor burden in 124 patients, prior to and during therapy. Subsequently, we used the computational models to explore an alternative strategy of “adaptive therapy” (AT), which includes defined treatment holidays, to improve the duration of “controlled disease” (CD). Simulations showed that AT could prolong CD in all three trials: 50.0% vs. 11.1% 50-month CD for a single agent approach in older adults (P = 0.0123), 80.4% vs. 58.8% 60-month CD for a multi-agent bortezomib based therapy (P = 0.0082), and 54.0% vs. 24.0% 60-month CD for a multi-agent lenalidomide based therapy (P < 0.0001). Increases in duration of CD resulted from the stabilization of tumor burden, which in turn would delay the growth of chemoresistant sub-populations in patients with partial (PR), or very good partial response (VGPR). These computational algorithms suggest that AT may provide an alternative and feasible therapeutic management strategy in MM.展开更多
Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (al...Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.展开更多
BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plu...BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.展开更多
目的:应用磁共振动态增强(DCE-MRI)半定量参数评估子宫肌瘤射频治疗的疗效。方法:回顾性分析2015年1月—2020年4月大庆油田总医院经射频治疗的52例子宫肌瘤患者的临床资料。术前及术后行磁共振动态增强检查,测量达峰时间(time to peak,T...目的:应用磁共振动态增强(DCE-MRI)半定量参数评估子宫肌瘤射频治疗的疗效。方法:回顾性分析2015年1月—2020年4月大庆油田总医院经射频治疗的52例子宫肌瘤患者的临床资料。术前及术后行磁共振动态增强检查,测量达峰时间(time to peak,TTP)、最大浓度(maximum concentration,MAX Conc)、时间—浓度曲线下面积(area under the time concentration curve,AUC)及最大斜率(maximum slope,MAX Slope),并利用四组参数对病灶进行疗效评估。结果:TTp、MAX Conc、AUC、MAX Slope比较,差异有统计学意义(Z=-4.025、-5.929、-6.011、-5.646,P<0.05)。结论:磁共振动态增强半定量参数TTp、MAX Conc、AUC、MAX Slope在术后疗效评估中具有重要意义,可作为有效的评估手段。展开更多
Efficient intracellular delivery of protein drugs is critical for protein therapy.The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect.However,co-deli...Efficient intracellular delivery of protein drugs is critical for protein therapy.The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect.However,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties.Herein,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)moieties.The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior.Under the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their endocytosis.Upon cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs.In cytoplasm,the high level of GSH removed the modification of 2-APBA on drugs.The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect.This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.展开更多
目的观察针刺配合穴位贴敷治疗卒中后排便障碍的临床疗效及其对患者营养状况、肠道菌落数及肛管直肠动力学影响。方法将94例卒中后排便障碍患者随机分为观察组和对照组,每组47例。两组均接受基础治疗,观察组采用针刺配合穴位贴敷治疗,...目的观察针刺配合穴位贴敷治疗卒中后排便障碍的临床疗效及其对患者营养状况、肠道菌落数及肛管直肠动力学影响。方法将94例卒中后排便障碍患者随机分为观察组和对照组,每组47例。两组均接受基础治疗,观察组采用针刺配合穴位贴敷治疗,对照组采用单纯穴位贴敷治疗。观察两组治疗前后各项营养状况指标[转铁蛋白(transferrin,TRF)、前白蛋白(prealbumin,PA)、血清白蛋白(albumin,ALB)水平]、肠道菌落数指标[双歧杆菌、肠杆菌、乳杆菌计数及短链脂肪酸(short-chain fatty acids,SCFAs)含量]、肛管直肠动力学指标(直肠初始阈值、肛管静息压、肛管最大收缩压、直肠排便感觉阈值)、临床症状评分(排便困难、排便频率、排便时间和腹胀评分)、便秘评分系统(constipation scoring system,CSS)评分及便秘患者生活质量量表(patient assessment of constipation quality of life questionnaire,PAC-QOL)评分的变化情况,比较两组临床疗效。结果观察组总有效率为97.9%,明显高于对照组的83.0%(P<0.05)。两组治疗后各项营养状况指标、SCFAs含量及双歧杆菌、乳杆菌计数均较同组治疗前显著升高,肠杆菌计数、各项肛管直肠动力学指标、各项临床症状评分、CSS评分及PAC-QOL评分均显著降低,差异均具有统计学意义(P<0.05)。观察组治疗后各项营养状况指标、SCFAs含量及双歧杆菌、乳杆菌计数均明显高于对照组,肠杆菌计数、各项肛管直肠动力学指标、各项临床症状评分、CSS评分及PAC-QOL评分均明显低于对照组,差异均具有统计学意义(P<0.05)。结论在基础治疗的基础上,针刺配合穴位贴敷治疗卒中后排便障碍疗效确切,可改善患者营养状态、肛管直肠动力学指标和临床症状,提升SCFAs含量,调节肠道菌落微生态。展开更多
基金This work was supported by the National Natural Science Foundation of China(51773231)Shenzhen Science and Technology Project(JCYJ20190807160801664)the Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(2011A060901013).
文摘The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.
文摘This study describes the development of a cervical traction therapy simulation model that evaluates two types of the traction positions, namely the sitting position and the inclined position. An anatomically correct human skeleton model and two mechanical traction device models were constructed in simulations using a physics engine. The anterior and posterior intervertebral separations were measured at both positions with a series of traction forces (60N to 200N) and traction angles (10°? to 40°?). The result suggested that the sitting position caused the subject to lean forward and as a result led to excessive anterior compression when traction angle is over 20 degrees. The inclined position creates greater intervertebral separations on both the anterior and posterior sides than the sitting position. This suggests that the inclined position may be more effective in increasing intervertebral separation than the sitting position.
文摘This paper develops a generalized dynamical model to describe the interactive dynamics between normal cells, tumor cells, immune cells, drug therapy, electromagnetic field of the human cells, extracellular heat and fluid transfer, and intercellular fractional mass of Oxygen, cell acidity and Pancreatin enzyme. The overall dynamics stability, controllability and observability have been investigated. Moreover, Cesium therapy is considered as a control input to the 11-dimensional dynamics using state-feedback controlled system and pole placement technique. This approach is found to be effective in driving the desired rate of tumor cell kill and converging the system to healthy equilibrium state. Furthermore, the ranges of the system dynamics parameters which lead to instability and growth of tumor cells have been identified. Finally, simulation results are demonstrated to verify the effectiveness of the applied approach which can be implemented successfully to cancer patients.
文摘Purpose: We performed both, dosimetric and positional accuracy verification of dynamic tumor tracking (DTT) intensity modulated radiation therapy (IMRT), with the Vero4DRT system using a moving phantom (QUASAR respiratory motion platform;QUASAR phantom) and system log files. Methods: The QUASAR phantom was placed on a treatment couch. Measurement of the point dose and dose distribution was performed for conventional IMRT, with the QUASAR phantom static and moving;for DTT IMRT, this was performed with the phantom moving for pyramid shaped, prostate, paranasal sinus, and pancreas targets. The QUASAR phantom was driven by a sinusoidal signal in the superior-inferior direction. Furthermore, predicted positional errors induced by the Vero4DRT system and mechanical positional errors of the gimbal head, were calculated using the system log files. Results and Conclusion: For DTT IMRT, the dose at the evaluation point was within 3% compared with the verification plan, and the dose distribution in the passing rates of γ was 97.9%, with the criteria of 3% dose and 3 mm distance to agreement. The position error calculated from the log files was within 2 mm, suggesting the feasibility of employing DTT IMRT with high accuracy using the Vero4DRT system.
文摘This work was undertaken to see how Ru II complexes can be suitable for photodynamic therapy through theoretical prediction. For that, four Ru II complexes, α-RuCl<sub>2</sub>(Azpy)<sub>2</sub>, , and were used in unrestricted state by providing with no more energy than 2.68 eV. The unrestricted state allows the complex molecule to display each of its electrons in one orbital. All the calculations such as optimization, frequency and TD-DFT calculations were performed at WB97XD/Lanl2dz level. It resulted from this investigation that Ru II complexes are active for both mechanisms suitable for photodynamic therapy in presence or absence of <sup>3</sup>O<sub>2</sub>. Moreover, this reaction was assumed to take place only with Guanine DNA base as demonstrated in literature. Therefore, Guanine is admitted as the base most reacting with ruthenium complexes for photodynamic therapy. This work confirms our prediction regarding metallic complexes that are assumed to be photosensitized in condition that an electron must be isolated to favor the excitation. Nevertheless, Ru II complexes are found suitable for superficial therapy while Ru III must be active for deep therapy.
基金supported by the National Institutes of Health[Grant no.R01NS069726]the American Heart Association Grant in Aid Grant[Grant no.13GRNT17020004]to SD
文摘Astrocytes are specialized and most numerous glial cell type in the central nervous system and play important roles in physiology. Astrocytes are also critically involved in many neural disorders including focal ischemic stroke, a leading cause of brain injury and human death. One of the prominent pathological features of focal ischemic stroke is reactive astrogliosis and glial scar formation associated with morphological changes and proliferation. This review paper discusses the recent advances in spatial and temporal dynamics of morphology and proliferation of reactive astrocytes after ischemic stroke based on results from experimental animal studies. As reactive astrocytes exhibit stem cell-like properties, knowledge of dynamics of reactive astrocytes and glial scar formation will provide important insiehts for astrocvte-based cell therapy in stroke.
基金Present calculations were performed at the Texas Tech University High Performance Computer Center and the Texas Advanced Computing Center at the University of Texas at Austin.Prof.Morales acknowledges financial support from the Cancer Prevention and Research Institute of Texas(CPRIT)grant RP140478.Prof.Yan acknowledges the financial support from the National Natural Science Foundation of China(No.21373064)and the Program for Innovative Research Team of Guizhou Province(No.QKTD[2014]4021).
文摘The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simplest-level electron nuclear dynamics(SLEND)method.SLEND describes nuclei via classical mechanics and electrons with a singledeterminantal Thouless wavefunction.The 3402 SLEND conducted simulations from 42 independent CO2 target orientations provide a full description of all the reactive processes and their mechanisms in this system:non-charge-transfer scattering(NCTS),charge-transfer scattering(CTS),and single C=O bond dissociation;all this valuable information about reactivity is not accessible experimentally.Numerous details of the projectile scattering patterns are provided,including the appearance and coalescence of primary and secondary rainbow angles as a function of the target orientation.SLEND NCTS and CTS differential cross sections(DCSs)are evaluated in conjunction with advanced semi-classical techniques.SLEND NCTS DCS agrees well with its experimental counterpart at all the measured scattering angles,whereas SLEND CTS DCS agrees well at high scattering angles but less satisfactorily at lower ones.Remarkably,both NCTS and CTS SLEND DCSs predict the primary rainbow angle signatures in agreement with the experiment.
文摘This study aims to validate the accuracy of a cervical traction therapy simulation model by comparing the intervertebral separations of six asymptomatic male adults when traction was applied to their cervical spines. The subjects were tested on two mechanical traction devices, representing the inclined and sitting positions. A total of 55 radiographic images of their cervical spines were taken before and during traction. The result showed statistically significant intervertebral space changes in the inclined position but the changes in the sitting position were not statistically significant. The observed changes of the cervical spine were used to adjust parameters of the traction therapy model, which contains a human model with cervical spine built with springs and dampers and two traction devices in inclined and sitting positions. A series of traction forces and traction angles were applied to the model to simulate the actual parameters used in the experiment and the new model was used to evaluate the two traction positions. The result suggested that inclined position creates greater intervertebral separations on the posterior sides. Differences in separations due to age were not observed in both positions. The result also suggested that the inclined position provides better control in positioning the separations at different spinal segments than the sitting position.
文摘This paper uses a molecular dynamics (MD) method for intensity-modulated proton therapy treatment planning optimization to overcome the problem of gradient-based optimization methods such as quasi-Newton, which is sensitive to starting conditions and is easily trapped in local minima. We implemented a molecular dynamics (MD) method and a quasi-Newton method for plan optimization. Three types of cancer cases, prostate, head-and-neck and lung cancer, were tested with three starting different initial conditions. Overall, the MD method consistently resulted in solutions with lower objective function values (OFVs) compared to those from the quasi-Newton algorithm. Furthermore, the MD method converged on the same OFV regardless of its initial starting points used for the prostate cancer case.
文摘This paper is concerned with Hepato-Cellular Carcinoma (HCC) patients treated naturopathic agents. Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents. The great effect is seen in patients treated with at least 4 agents that include Cordyceps sinensis. This greater certainty of patient survival without toxic side effects is significant benefit comparing with the conventional therapy. Treatment of HCC with a regimen of ≥4 agents prepared from natural products is associated with greater certainty of patient survival in a substantial portion of patients. The information dynamic model for certainty of patient survival is derived based on fluid mechanics, where a series of approximate solutions of the flow between two parallel flat walls, one of which is at rest, the other is suddenly accelerated from the rest to a constant velocity are used. The kinetic energy of certainty of patient survival decreases with increasing time, while the potential energy increases with increasing time. Total mechanical energy of patients treated with 4 or more agents is smaller than that treated with 3 or fewer agents. The kinetic energy (potential energy) of patients treated with 4 or more agents decreases (increases) more slower than the kinetic energy (potential energy) of patients treated with 3 or fewer agents.
文摘Most patients with multiple myeloma (MM) respond well to initial therapy, but invariably relapse due to evolution of resistant phenotypes. Here we examine the evolutionary dynamics of proliferation of resistant MM phenotypes during therapy. By applying computational models to data from three clinical trials for newly diagnosed MM patients, we have quantified the size and level of chemoresistance of subpopulations within the tumor burden in 124 patients, prior to and during therapy. Subsequently, we used the computational models to explore an alternative strategy of “adaptive therapy” (AT), which includes defined treatment holidays, to improve the duration of “controlled disease” (CD). Simulations showed that AT could prolong CD in all three trials: 50.0% vs. 11.1% 50-month CD for a single agent approach in older adults (P = 0.0123), 80.4% vs. 58.8% 60-month CD for a multi-agent bortezomib based therapy (P = 0.0082), and 54.0% vs. 24.0% 60-month CD for a multi-agent lenalidomide based therapy (P < 0.0001). Increases in duration of CD resulted from the stabilization of tumor burden, which in turn would delay the growth of chemoresistant sub-populations in patients with partial (PR), or very good partial response (VGPR). These computational algorithms suggest that AT may provide an alternative and feasible therapeutic management strategy in MM.
文摘Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.
基金Supported by The Twelfth Five-Year Project on Tackling Key Problems of National Science and Technology,No2012ZX10001-003Sichuan Province Health Commission,No. 130430 and No. 17PJ070Chengdu Municipal Health Commission,No. 2019079
文摘BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.
文摘目的:应用磁共振动态增强(DCE-MRI)半定量参数评估子宫肌瘤射频治疗的疗效。方法:回顾性分析2015年1月—2020年4月大庆油田总医院经射频治疗的52例子宫肌瘤患者的临床资料。术前及术后行磁共振动态增强检查,测量达峰时间(time to peak,TTP)、最大浓度(maximum concentration,MAX Conc)、时间—浓度曲线下面积(area under the time concentration curve,AUC)及最大斜率(maximum slope,MAX Slope),并利用四组参数对病灶进行疗效评估。结果:TTp、MAX Conc、AUC、MAX Slope比较,差异有统计学意义(Z=-4.025、-5.929、-6.011、-5.646,P<0.05)。结论:磁共振动态增强半定量参数TTp、MAX Conc、AUC、MAX Slope在术后疗效评估中具有重要意义,可作为有效的评估手段。
基金This work was financially supported by the National Key R&D Program of China(Nos.2022YFA1205703 and 2022YFA1205702)the National Natural Science Foundation of China(Nos.51773099,51933006 and 52103183)Haihe Laboratory of Sustainable Chemical Transformations(No.YYJC202102).
文摘Efficient intracellular delivery of protein drugs is critical for protein therapy.The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect.However,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties.Herein,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)moieties.The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior.Under the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their endocytosis.Upon cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs.In cytoplasm,the high level of GSH removed the modification of 2-APBA on drugs.The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect.This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.
文摘目的观察针刺配合穴位贴敷治疗卒中后排便障碍的临床疗效及其对患者营养状况、肠道菌落数及肛管直肠动力学影响。方法将94例卒中后排便障碍患者随机分为观察组和对照组,每组47例。两组均接受基础治疗,观察组采用针刺配合穴位贴敷治疗,对照组采用单纯穴位贴敷治疗。观察两组治疗前后各项营养状况指标[转铁蛋白(transferrin,TRF)、前白蛋白(prealbumin,PA)、血清白蛋白(albumin,ALB)水平]、肠道菌落数指标[双歧杆菌、肠杆菌、乳杆菌计数及短链脂肪酸(short-chain fatty acids,SCFAs)含量]、肛管直肠动力学指标(直肠初始阈值、肛管静息压、肛管最大收缩压、直肠排便感觉阈值)、临床症状评分(排便困难、排便频率、排便时间和腹胀评分)、便秘评分系统(constipation scoring system,CSS)评分及便秘患者生活质量量表(patient assessment of constipation quality of life questionnaire,PAC-QOL)评分的变化情况,比较两组临床疗效。结果观察组总有效率为97.9%,明显高于对照组的83.0%(P<0.05)。两组治疗后各项营养状况指标、SCFAs含量及双歧杆菌、乳杆菌计数均较同组治疗前显著升高,肠杆菌计数、各项肛管直肠动力学指标、各项临床症状评分、CSS评分及PAC-QOL评分均显著降低,差异均具有统计学意义(P<0.05)。观察组治疗后各项营养状况指标、SCFAs含量及双歧杆菌、乳杆菌计数均明显高于对照组,肠杆菌计数、各项肛管直肠动力学指标、各项临床症状评分、CSS评分及PAC-QOL评分均明显低于对照组,差异均具有统计学意义(P<0.05)。结论在基础治疗的基础上,针刺配合穴位贴敷治疗卒中后排便障碍疗效确切,可改善患者营养状态、肛管直肠动力学指标和临床症状,提升SCFAs含量,调节肠道菌落微生态。