BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic...BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.展开更多
Hematopoeitic stem cell transplantation(HSCT)using a haploidentical family donor(HAPLO)was long thought to be non-feasible,essentially because of HLA incompatibility leading to graft rejection,severe acute(aGVH)and ch...Hematopoeitic stem cell transplantation(HSCT)using a haploidentical family donor(HAPLO)was long thought to be non-feasible,essentially because of HLA incompatibility leading to graft rejection,severe acute(aGVH)and chronic(cGVH)graft versus host disease(GVH),severe infections and unacceptable nonrelapse mortality(NRM).The group in Perugia in the last decade of the past century[1],was the first to be successful by initiating a positive selection of CD34+cells from peripheral blood stem cell(PBSC)collections,providing T cell depleted grafts with very high doses of CD34+cells to be infused.When combined with intensive conditioning regimen and profound immunosuppression,the Perugia group obtained the first demonstration of feasibility and efficacy.They later improved their results in acute myeloid leukemia(AML)by showing that a mismatch for natural killer(NK)cells in the killer-cell immunoglobulin-like receptor(KIR)-human leukocyte-antigen class I(HLA1)donor to recipient direction[2]decreased considerably the relapse incidence(RI).Unfortunately this approach was associated with severe infections,a high NRM and in addition was cumbersome and difficult to reproduce in other non-expert centers.展开更多
Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortal...Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.展开更多
This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The inp...This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.展开更多
INTERNAL DOSE RESEARCH PAPERS INTDOSKIT:An R-Code for Calculation of Dose Coefficients and Studying Their Uncertainties Bastian Breustedt 1,Niranjan Chavan 2,Thomas Makumbi 2(1.Karlsruhe Institute of Technology,Instit...INTERNAL DOSE RESEARCH PAPERS INTDOSKIT:An R-Code for Calculation of Dose Coefficients and Studying Their Uncertainties Bastian Breustedt 1,Niranjan Chavan 2,Thomas Makumbi 2(1.Karlsruhe Institute of Technology,Institute of Biomedical Engineering(IBT),Fritz-Haber-Weg 1,D-76131 Karlsruhe,Germany;2.Karlsruhe Institute of Technology,Institute for Thermal Energy Technology and Safety(ITES),Hermann-von-Helmholtz-Platz 1,76344 EggensteinLeopoldshafen,Germany)Abstract:An R-code,which allows the calculation of the time dependent activity distribution based on ICRP reference models,the number of decays in a commitment period,and the dose coefficients for tissues and organs of the human body,has been developed.R Language was chosen due to its powerful mathematical and statistical modeling features,as well as its graphical capabilities.展开更多
Evaluation of a Commercially Available Radiochromic Film for Use as a Complementary Dosimeter for Rapid In-field Low Photon Equivalent Radiation Dose (≤50 mSv) Monitoring Nicky Nivi1, Helen Moise1,2, Ana Pejovic'...Evaluation of a Commercially Available Radiochromic Film for Use as a Complementary Dosimeter for Rapid In-field Low Photon Equivalent Radiation Dose (≤50 mSv) Monitoring Nicky Nivi1, Helen Moise1,2, Ana Pejovic'-Milic'1(1. Department of Physics, Toronto Metropolitan University, 350 Victoria Street, Toronto, Ontario, M5B 2K3;2. Autonomous and Radiological Technologies Section, Defense Research and Development Canada, PO Box 4000 Stn Main,Medicine Hat, Alberta, T1A 8K6).展开更多
With the rapid development of computed tomography(CT)technology,the widespread use of CT examinations in the evaluation of chest diseases in pediatrics has raised extensive concerns about radiation issues.This review ...With the rapid development of computed tomography(CT)technology,the widespread use of CT examinations in the evaluation of chest diseases in pediatrics has raised extensive concerns about radiation issues.This review first systematically summarizes the factors influencing radiation dose(detector,tube voltage,tube current-time product,field of view,and reconstruction algorithms)in pediatric chest computed tomography examinations.Methods to reduce radia-tion dose are also discussed,including the utilization of filters,automatic tube current modulation,automatic tube voltage selection,and organ dose modulation.Finally,the methods for individualized radiation dose calculation in pediatric chest CT examinations:effective dose,CT dosimetry software,Size-Specific Dose Estimate,and the Monte Carlo method are reviewed.Radiation exposure re-duction is a multifaceted issue.This review aims to provide an optimal scanning scheme for pediatric chest CT from different perspectives.展开更多
BACKGROUND Primary ciliary dyskinesia(PCD)is a rare condition characterised by dysmotile,immotile,or absent cilia.As a result of the impairment in respiratory mucociliary clearance,patients with PCD typically develop ...BACKGROUND Primary ciliary dyskinesia(PCD)is a rare condition characterised by dysmotile,immotile,or absent cilia.As a result of the impairment in respiratory mucociliary clearance,patients with PCD typically develop neonatal respiratory distress,nasal congestion,otitis media and recurrent respiratory infections leading to bronchiectasis and structural lung changes.These changes have been shown by chest computed tomography(CT)to develop in infancy and early childhood.Recent development and refinement of radiation-reducing CT techniques have allowed significant radiation dose reductions,with chest CT doses now in the range of chest radiography(CR).AIM To evaluate the efficacy of ultra-low dose CT(ULDCT)chest in identifying pulmonary changes within a PCD paediatric patient cohort.METHODS Paediatric patients with PCD who presented for routine clinical outpatient follow-up within the study period,were eligible for inclusion in the study.ULDCT and CR were performed on these patients and the results compared.Comparison metrics included radiation dose,subjective and objective image quality and disease severity.RESULTS Six paediatric patients(mean age 9 years)underwent clinically indicated ULDCT chest examinations and CR for surveillance of their PCD.The mean effective dose was 0.08±0.02 mSv,a dose that approximates that of a frontal and lateral chest radiograph.The average Brody II score across the entire cohort was 12.92,with excellent interrater reliability and intra-class correlation coefficient(ICC)of 0.98.The average Chrispin-Norman score on CR was 1 with excellent inter-rater reliability and ICC of 0.92.CONCLUSION ULDCT demonstrates superior diagnostic capabilities,minimal radiation dose penalty,and high interobserver reliability in comparison to CR.Thus,we advocate for ULDCT to be the preferred modality for surveillance imaging in paediatric PCD.展开更多
BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with an...BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with and without prominent nega-tive symptoms(PNS).AIM To evaluate the effectiveness and safety of blonanserin monotherapy for first-episode schizophrenia in real-world clinical settings and to explore the efficacy and safety of different doses of blonanserin for patients with PNS and without PNS.METHODS A 12-week,multicenter,prospective post-marketing surveillance was conducted.In this study,we included patients with first-episode schizophrenia who received blonanserin monotherapy.Patients were divided into those with PNS and without PNS,based on the Brief Psychiatric Rating Scale(BPRS)negative symptoms subscale scores.Additionally,patients were labeled as high-dose and low-dose was evaluated through the incidence of adverse drug reactions(ADRs).RESULTS A total of 653 patients were included in the analysis,with 613 completing the study.The BPRS total score decreased significantly from 47.94±16.31 at baseline to 26.88±9.47 at 12 weeks(P<0.001).A significant interaction of PNS×dose×time was observed for BPRS total scores(F=3.47,P=0.040)and negative symptom subscale scores(F=6.76,P=0.002).In the PNS group,the high-dose group showed greater reductions in BPRS total scores(P=0.001)and negative symptom subscale scores(P=0.003)than the low-dose group in week 12.In the without PNS group,no significant difference was observed between the high-dose and low-dose groups at any visit.Most adverse reactions were mild or moderate,with extrapyramidal symptoms(9.3%)being most common;1.5%of patients gained≥7%body weight at 12 weeks.CONCLUSION Blonanserin effectively alleviated the clinical symptoms of first-episode schizophrenia with an acceptable safety profile.High-dose blonanserin is particularly beneficial for patients with PNS in the acute phase of first-episode schizophrenia.However,due to the limitation of ADR reporting the real world,the ADR incidence observed in this study may be underestimated.展开更多
This study systematically investigates natural radioactivity in groundwater from the densely populated eastern Gonghe Basin in Qinghai Province,aiming to reveal its spatial distribution,origins,and potential health ri...This study systematically investigates natural radioactivity in groundwater from the densely populated eastern Gonghe Basin in Qinghai Province,aiming to reveal its spatial distribution,origins,and potential health risks.The characteristics of gross-αand gross-βactivities,as well as the concentrations of nuclide including^(238)U,^(232)Th,and^(226)Ra,have been investigated in groundwater samples from 12 groups encompassing various types such as hot springs and artesian wells across different aquifer systems.Correlation analysis and dose estimation models were applied to preliminary estimate the radiation exposure to local residents and to explore the genesis and hazards of natural radioactivity in groundwater.Results indicate that overall groundwater radioactivity in the Gonghe Basin remains within acceptable limits,with mean gross-αand gross-βactivity concentrations of 0.32 Bq/L and 0.27 Bq/L,respectively.Approximately 83.33%of samples comply with relevant national standards.However,two fault-controlled high-temperature spring samples exhibited gross-αactivity exceeding regulatory limits,with one also showing elevated gross-βactivity surpassing China's Class III groundwater quality standards for radioactivity.Furthermore,single-radionuclideαradioactivity from^(230)Th,^(226)Ra,^(210)Po,and^(232)Th exceeded regulatory thresholds in some samples,suggesting potential long-term health risks.While most samples complied with effective dose limits,four showed^(210)Poαradioactivity exceedances within controllable risk ranges.The findings suggest that groundwater radioactivity in the region is primarily controlled by geological structures,lithology,and hydrothermal conditions,with fault zones and high-temperature environments serving as key factors in radionuclide enrichment.This research provides scientific foundation for the sustainable development of geothermal resources and the prevention of radioactive water contamination.Continuous monitoring of high-radioactivity hot springs and prudent resource utilization are recommended.展开更多
Increasing concern over the amount of insecticide residues in food has encouraged research for ecologically sound strategies to effectively manage stored-product insect pests and protect living organisms and the envir...Increasing concern over the amount of insecticide residues in food has encouraged research for ecologically sound strategies to effectively manage stored-product insect pests and protect living organisms and the environment. Botanicals were evaluated as potential alternatives to control maize weevil, Sitophilus zeamais Motschulsky, in stored sorghum, Sorghum bicolor (L.) Moench. Beetles and moths of stored grain at farm and consumer levels damage 5 - 35% worldwide and >40% in tropical countries. Maize weevil is the most damaging storage insect of sorghum grain. Management of storage insects relies on insecticides that leave residues in food and the environment. Treatments were powders of neem bark, Azadirachta indica;mesquite pods, Prosopis glandulosa;milkweed leaves, Asclepias speciosa;and a check (no botanical powder). Eight newly emerged maize weevils were provided 5 g of Malisor-84 grain treated with three doses of each plant powder. Every 2 days, data were recorded on the number of adults killed by each treatment. Percentage killed was calculated by dose per treatment and compared with the check. Grain loss was calculated based on initial and final weights. LD50 was determined by probit analysis, and associations between variables were assessed by simple linear correlation. Powder of mesquite and milkweed at 0.2 g were more effective than neem or the check in killing S. zeamais (>90%) and reducing grain damage (34 - 35.2%) and weight loss (0.8%). Milkweed at 0.1 g and neem at 0.2 g killed 78.1% of weevils. Neem at 0.05 g was slow acting, resulting in 62.5% dead and more grain damage (59.5%) and weight loss (3.6%). Botanicals at low doses (LD50 = 0.2 - 0.4 g) showed efficacy in controlling maize weevils and are recommended alternatives to guarantee quantity and quality of stored cereal grains.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is highly prevalent worldwide,and rising antibiotic resistance has reduced the efficacy of standard therapy,underscoring the need for simplified and better-tolerated r...BACKGROUND Helicobacter pylori(H.pylori)infection is highly prevalent worldwide,and rising antibiotic resistance has reduced the efficacy of standard therapy,underscoring the need for simplified and better-tolerated regimens.AIM To evaluate the efficacy,safety,and optimal dosing of vonoprazan(VPZ)-amoxicillin(AMO)dual therapy in a non-inferiority randomized trial for H.pylori eradication.METHODS In this multi-center,randomized trial conducted at 17 hospitals in Sichuan Province,China,1717 adults with confirmed infection were assigned(1:1:1)to 14-day regimens:(1)VPZ 20 mg BID+AMO 0.5 g QID;(2)0.75 g QID;or(3)1.0 g TID.The primary endpoint was the eradication rate based on intention-to-treat(ITT)and per-protocol(PP)analyses;secondary endpoints included adverse events(AEs)and treatment compliance.RESULTS Eradication rates were consistently high(92.35%-97.43%).In the 0.5 g QID group,ITT and PP eradication rates were 93.3%(95%CI:91.2-95.1)and 97.4%(95%CI:95.7-98.5),respectively,with no significant differences among groups(P>0.05).Compliance ranged from 98.1%to 98.3%,and AEs were infrequent(5.2%-7.5%),predominantly mild gastrointestinal symptoms,which occurred least often in the 0.5 g QID group.CONCLUSION VPZ-AMO dual therapy achieved excellent eradication,safety,and patient compliance.All regimens were similarly effective,whereas the 0.5 g QID dosing strategy offered the most favorable balance of efficacy and tolerability,supporting its use as a first-line option in high-prevalence settings.展开更多
Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to th...Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to their pathophysiological properties,including cognitive dysfunction,Alzheimer's disease (AD) and other dementias,Parkinson's disease,and motor neuron disease.The increased oxidative stress and neuro-inflammatory events contribute to neuronal atrophy and death in NDDs~([1]).Nitric oxide in the central nervous system has several functions,including the regulation of synaptic plasticity and neurosecretion.The physiological amount of nitric oxide is neuroprotective,whereas higher doses are noticeably neurotoxic~([2]).展开更多
BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilit...BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.展开更多
Radiation doses to patients in diagnostics and interventional radiology need to be optimized to comply with the principles of radiation protection in medical practice. This involves using specific detectors with respe...Radiation doses to patients in diagnostics and interventional radiology need to be optimized to comply with the principles of radiation protection in medical practice. This involves using specific detectors with respective diagnostic beams to carry out quality control/quality assurance tests needed to optimize patient doses in the hospital. Semiconductor detectors are used in dosimetry to verify the equipment performance and dose to patients. This work aims to assess the performance, energy dependence, and response of five commercially available semiconductor detectors in RQR, RQR-M, RQA, and RQT at Secondary Standard Dosimetry for clinical applications. The diagnostic beams were generated using Exradin A4 reference ion chamber and PTW electrometer. The ambient temperature and pressure were noted for KTP correction. The detectors designed for RQR showed good performance in RQT beams and vice versa. The detectors designed for RQR-M displayed high energy dependency in other diagnostic beams. The type of diagnostic beam quality determines the response of semiconductor detectors. Therefore, a detector should be calibrated according to the beam qualities to be measured.展开更多
The radiation-sensitive field effect transistors(RADFET)radiation dosimeter is a type of radiation detector based on the total dose effects of the p-channel metal-oxide-semiconductor(PMOS)transistor.The RADFET chip wa...The radiation-sensitive field effect transistors(RADFET)radiation dosimeter is a type of radiation detector based on the total dose effects of the p-channel metal-oxide-semiconductor(PMOS)transistor.The RADFET chip was fabricated in United Microelectronics Center 8-inch process with a six-layer photomask.The chip including two identical PMOS transistors,occupies a size of 610μm×610μm.Each PMOS has a W/L ratio of 300μm/50μm,and a 400 nm thick gate oxide,which is formed by a dry-wet-dry oxygen process.The wet oxygen-formed gate oxide with more traps can capture more holes during irradiation,thus significantly changing the PMOS threshold voltage.Pre-irradiation measurement results from ten test chips show that the initial average voltage of the PMOS is 1.961 V with a dispersion of 5.7%.The irradiation experiment is conducted in a cobalt source facility with a dose rate of 50 rad(Si)/s.During irradiation,a constant current source circuit of 10μA was connected to monitoring the shift in threshold voltage under different total dose.When the total dose is 100 krad(Si),the shift in threshold voltage was approximately 1.37 V,which demonstrates that an excellent radiation function was achieved.展开更多
A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a signifi...A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a significant advancement in personalized radiotherapy by improving accuracy and reducing treatment-related toxicity.The model demonstrated strong predictive performance with R-values above 0.8,indicating its potential to improve treatment consistency.However,concerns arise from the small sample size and exclusion criteria,which may limit generalizability.Future studies should incorporate larger,more diverse patient cohorts,explore potential confounding factors such as tumor characteristics and delivery technique variability,and address the long-term effects of SBRT.展开更多
文摘BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.
文摘Hematopoeitic stem cell transplantation(HSCT)using a haploidentical family donor(HAPLO)was long thought to be non-feasible,essentially because of HLA incompatibility leading to graft rejection,severe acute(aGVH)and chronic(cGVH)graft versus host disease(GVH),severe infections and unacceptable nonrelapse mortality(NRM).The group in Perugia in the last decade of the past century[1],was the first to be successful by initiating a positive selection of CD34+cells from peripheral blood stem cell(PBSC)collections,providing T cell depleted grafts with very high doses of CD34+cells to be infused.When combined with intensive conditioning regimen and profound immunosuppression,the Perugia group obtained the first demonstration of feasibility and efficacy.They later improved their results in acute myeloid leukemia(AML)by showing that a mismatch for natural killer(NK)cells in the killer-cell immunoglobulin-like receptor(KIR)-human leukocyte-antigen class I(HLA1)donor to recipient direction[2]decreased considerably the relapse incidence(RI).Unfortunately this approach was associated with severe infections,a high NRM and in addition was cumbersome and difficult to reproduce in other non-expert centers.
基金supported by the National Natural Science Foundation of China(grant numbers 82204127 and 72204172)。
文摘Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.
基金supported by the National Natural Science Foundation of China(U2241221).
文摘This article introduces a novel 20 V radiation-hardened high-voltage metal-oxide-semiconductor field-effect transistor(MOSFET)driver with an optimized input circuit and a drain-surrounding-source(DSS)structure.The input circuit of a conventional inverter consists of a thick-gate-oxide n-type MOSFET(NMOS).These conventional drivers can tolerate a total ionizing dose(TID)of up to 100 krad(Si).In contrast,the proposed comparator input circuit uses both a thick-gate-oxide p-type MOSFET(PMOS)and thin-gate-oxide NMOS to offer a high input voltage and higher TID tolerance.Because the thick-gate-oxide PMOS and thin-gate-oxide NMOS collectively provide better TID tolerance than the thick-gate-oxide NMOS,the circuit exhibits enhanced TID tolerance of>300 krad(Si).Simulations and experimental date indicate that the DSS structure reduces the probability of unwanted parasitic bipolar junction transistor activation,yielding a better single-event effect tolerance of over 81.8 MeVcm^(2)mg^(-1).The innovative strategy proposed in this study involves circuit and layout design optimization,and does not require any specialized process flow.Hence,the proposed circuit can be manufactured using common commercial 0.35μm BCD processes.
文摘INTERNAL DOSE RESEARCH PAPERS INTDOSKIT:An R-Code for Calculation of Dose Coefficients and Studying Their Uncertainties Bastian Breustedt 1,Niranjan Chavan 2,Thomas Makumbi 2(1.Karlsruhe Institute of Technology,Institute of Biomedical Engineering(IBT),Fritz-Haber-Weg 1,D-76131 Karlsruhe,Germany;2.Karlsruhe Institute of Technology,Institute for Thermal Energy Technology and Safety(ITES),Hermann-von-Helmholtz-Platz 1,76344 EggensteinLeopoldshafen,Germany)Abstract:An R-code,which allows the calculation of the time dependent activity distribution based on ICRP reference models,the number of decays in a commitment period,and the dose coefficients for tissues and organs of the human body,has been developed.R Language was chosen due to its powerful mathematical and statistical modeling features,as well as its graphical capabilities.
文摘Evaluation of a Commercially Available Radiochromic Film for Use as a Complementary Dosimeter for Rapid In-field Low Photon Equivalent Radiation Dose (≤50 mSv) Monitoring Nicky Nivi1, Helen Moise1,2, Ana Pejovic'-Milic'1(1. Department of Physics, Toronto Metropolitan University, 350 Victoria Street, Toronto, Ontario, M5B 2K3;2. Autonomous and Radiological Technologies Section, Defense Research and Development Canada, PO Box 4000 Stn Main,Medicine Hat, Alberta, T1A 8K6).
基金Supported by the Key Natural Science Project of the Anhui Provincial Education Department Under,No.KJ2021A0746.
文摘With the rapid development of computed tomography(CT)technology,the widespread use of CT examinations in the evaluation of chest diseases in pediatrics has raised extensive concerns about radiation issues.This review first systematically summarizes the factors influencing radiation dose(detector,tube voltage,tube current-time product,field of view,and reconstruction algorithms)in pediatric chest computed tomography examinations.Methods to reduce radia-tion dose are also discussed,including the utilization of filters,automatic tube current modulation,automatic tube voltage selection,and organ dose modulation.Finally,the methods for individualized radiation dose calculation in pediatric chest CT examinations:effective dose,CT dosimetry software,Size-Specific Dose Estimate,and the Monte Carlo method are reviewed.Radiation exposure re-duction is a multifaceted issue.This review aims to provide an optimal scanning scheme for pediatric chest CT from different perspectives.
文摘BACKGROUND Primary ciliary dyskinesia(PCD)is a rare condition characterised by dysmotile,immotile,or absent cilia.As a result of the impairment in respiratory mucociliary clearance,patients with PCD typically develop neonatal respiratory distress,nasal congestion,otitis media and recurrent respiratory infections leading to bronchiectasis and structural lung changes.These changes have been shown by chest computed tomography(CT)to develop in infancy and early childhood.Recent development and refinement of radiation-reducing CT techniques have allowed significant radiation dose reductions,with chest CT doses now in the range of chest radiography(CR).AIM To evaluate the efficacy of ultra-low dose CT(ULDCT)chest in identifying pulmonary changes within a PCD paediatric patient cohort.METHODS Paediatric patients with PCD who presented for routine clinical outpatient follow-up within the study period,were eligible for inclusion in the study.ULDCT and CR were performed on these patients and the results compared.Comparison metrics included radiation dose,subjective and objective image quality and disease severity.RESULTS Six paediatric patients(mean age 9 years)underwent clinically indicated ULDCT chest examinations and CR for surveillance of their PCD.The mean effective dose was 0.08±0.02 mSv,a dose that approximates that of a frontal and lateral chest radiograph.The average Brody II score across the entire cohort was 12.92,with excellent interrater reliability and intra-class correlation coefficient(ICC)of 0.98.The average Chrispin-Norman score on CR was 1 with excellent inter-rater reliability and ICC of 0.92.CONCLUSION ULDCT demonstrates superior diagnostic capabilities,minimal radiation dose penalty,and high interobserver reliability in comparison to CR.Thus,we advocate for ULDCT to be the preferred modality for surveillance imaging in paediatric PCD.
文摘BACKGROUND Blonanserin,a novel antipsychotic,has demonstrated efficacy in treating both positive and negative symptoms.However,limited research exists on its dose-dependent effectiveness and safety in patients with and without prominent nega-tive symptoms(PNS).AIM To evaluate the effectiveness and safety of blonanserin monotherapy for first-episode schizophrenia in real-world clinical settings and to explore the efficacy and safety of different doses of blonanserin for patients with PNS and without PNS.METHODS A 12-week,multicenter,prospective post-marketing surveillance was conducted.In this study,we included patients with first-episode schizophrenia who received blonanserin monotherapy.Patients were divided into those with PNS and without PNS,based on the Brief Psychiatric Rating Scale(BPRS)negative symptoms subscale scores.Additionally,patients were labeled as high-dose and low-dose was evaluated through the incidence of adverse drug reactions(ADRs).RESULTS A total of 653 patients were included in the analysis,with 613 completing the study.The BPRS total score decreased significantly from 47.94±16.31 at baseline to 26.88±9.47 at 12 weeks(P<0.001).A significant interaction of PNS×dose×time was observed for BPRS total scores(F=3.47,P=0.040)and negative symptom subscale scores(F=6.76,P=0.002).In the PNS group,the high-dose group showed greater reductions in BPRS total scores(P=0.001)and negative symptom subscale scores(P=0.003)than the low-dose group in week 12.In the without PNS group,no significant difference was observed between the high-dose and low-dose groups at any visit.Most adverse reactions were mild or moderate,with extrapyramidal symptoms(9.3%)being most common;1.5%of patients gained≥7%body weight at 12 weeks.CONCLUSION Blonanserin effectively alleviated the clinical symptoms of first-episode schizophrenia with an acceptable safety profile.High-dose blonanserin is particularly beneficial for patients with PNS in the acute phase of first-episode schizophrenia.However,due to the limitation of ADR reporting the real world,the ADR incidence observed in this study may be underestimated.
文摘This study systematically investigates natural radioactivity in groundwater from the densely populated eastern Gonghe Basin in Qinghai Province,aiming to reveal its spatial distribution,origins,and potential health risks.The characteristics of gross-αand gross-βactivities,as well as the concentrations of nuclide including^(238)U,^(232)Th,and^(226)Ra,have been investigated in groundwater samples from 12 groups encompassing various types such as hot springs and artesian wells across different aquifer systems.Correlation analysis and dose estimation models were applied to preliminary estimate the radiation exposure to local residents and to explore the genesis and hazards of natural radioactivity in groundwater.Results indicate that overall groundwater radioactivity in the Gonghe Basin remains within acceptable limits,with mean gross-αand gross-βactivity concentrations of 0.32 Bq/L and 0.27 Bq/L,respectively.Approximately 83.33%of samples comply with relevant national standards.However,two fault-controlled high-temperature spring samples exhibited gross-αactivity exceeding regulatory limits,with one also showing elevated gross-βactivity surpassing China's Class III groundwater quality standards for radioactivity.Furthermore,single-radionuclideαradioactivity from^(230)Th,^(226)Ra,^(210)Po,and^(232)Th exceeded regulatory thresholds in some samples,suggesting potential long-term health risks.While most samples complied with effective dose limits,four showed^(210)Poαradioactivity exceedances within controllable risk ranges.The findings suggest that groundwater radioactivity in the region is primarily controlled by geological structures,lithology,and hydrothermal conditions,with fault zones and high-temperature environments serving as key factors in radionuclide enrichment.This research provides scientific foundation for the sustainable development of geothermal resources and the prevention of radioactive water contamination.Continuous monitoring of high-radioactivity hot springs and prudent resource utilization are recommended.
文摘Increasing concern over the amount of insecticide residues in food has encouraged research for ecologically sound strategies to effectively manage stored-product insect pests and protect living organisms and the environment. Botanicals were evaluated as potential alternatives to control maize weevil, Sitophilus zeamais Motschulsky, in stored sorghum, Sorghum bicolor (L.) Moench. Beetles and moths of stored grain at farm and consumer levels damage 5 - 35% worldwide and >40% in tropical countries. Maize weevil is the most damaging storage insect of sorghum grain. Management of storage insects relies on insecticides that leave residues in food and the environment. Treatments were powders of neem bark, Azadirachta indica;mesquite pods, Prosopis glandulosa;milkweed leaves, Asclepias speciosa;and a check (no botanical powder). Eight newly emerged maize weevils were provided 5 g of Malisor-84 grain treated with three doses of each plant powder. Every 2 days, data were recorded on the number of adults killed by each treatment. Percentage killed was calculated by dose per treatment and compared with the check. Grain loss was calculated based on initial and final weights. LD50 was determined by probit analysis, and associations between variables were assessed by simple linear correlation. Powder of mesquite and milkweed at 0.2 g were more effective than neem or the check in killing S. zeamais (>90%) and reducing grain damage (34 - 35.2%) and weight loss (0.8%). Milkweed at 0.1 g and neem at 0.2 g killed 78.1% of weevils. Neem at 0.05 g was slow acting, resulting in 62.5% dead and more grain damage (59.5%) and weight loss (3.6%). Botanicals at low doses (LD50 = 0.2 - 0.4 g) showed efficacy in controlling maize weevils and are recommended alternatives to guarantee quantity and quality of stored cereal grains.
基金Supported by Project Fund of the Health Commission of Sichuan Province,No.19PJ290。
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is highly prevalent worldwide,and rising antibiotic resistance has reduced the efficacy of standard therapy,underscoring the need for simplified and better-tolerated regimens.AIM To evaluate the efficacy,safety,and optimal dosing of vonoprazan(VPZ)-amoxicillin(AMO)dual therapy in a non-inferiority randomized trial for H.pylori eradication.METHODS In this multi-center,randomized trial conducted at 17 hospitals in Sichuan Province,China,1717 adults with confirmed infection were assigned(1:1:1)to 14-day regimens:(1)VPZ 20 mg BID+AMO 0.5 g QID;(2)0.75 g QID;or(3)1.0 g TID.The primary endpoint was the eradication rate based on intention-to-treat(ITT)and per-protocol(PP)analyses;secondary endpoints included adverse events(AEs)and treatment compliance.RESULTS Eradication rates were consistently high(92.35%-97.43%).In the 0.5 g QID group,ITT and PP eradication rates were 93.3%(95%CI:91.2-95.1)and 97.4%(95%CI:95.7-98.5),respectively,with no significant differences among groups(P>0.05).Compliance ranged from 98.1%to 98.3%,and AEs were infrequent(5.2%-7.5%),predominantly mild gastrointestinal symptoms,which occurred least often in the 0.5 g QID group.CONCLUSION VPZ-AMO dual therapy achieved excellent eradication,safety,and patient compliance.All regimens were similarly effective,whereas the 0.5 g QID dosing strategy offered the most favorable balance of efficacy and tolerability,supporting its use as a first-line option in high-prevalence settings.
文摘Dear Editor,Neurodegenerative disorders (NDDs) are agerelated disorders characterized by the deposition of abnormal forms of proteins or the progressive loss of neurons in the brain.NDDs are classified according to their pathophysiological properties,including cognitive dysfunction,Alzheimer's disease (AD) and other dementias,Parkinson's disease,and motor neuron disease.The increased oxidative stress and neuro-inflammatory events contribute to neuronal atrophy and death in NDDs~([1]).Nitric oxide in the central nervous system has several functions,including the regulation of synaptic plasticity and neurosecretion.The physiological amount of nitric oxide is neuroprotective,whereas higher doses are noticeably neurotoxic~([2]).
基金Supported by the Joint Innovation Project Funds of Huaqiao University,No.2022YX001。
文摘BACKGROUND Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma.Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities.However,limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells(HUC-MSCs)on established airway remodeling in experimental asthma.AIM To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin(OVA)-induced asthma.METHODS BALB/c mice underwent sensitization and were challenged using OVA.Control animals were administered a saline solution following the same protocol.HUC-MSCs were identified using flow cytometry.HUC-MSCs at incremental dosages(1×105,2×105,4×105)were injected via tail veins on day 30(the second after the final stimulation).After comparing each group and determining the optimal dose,supplement the optimal dose twice on day 30 and day 33(the second and fifth day after the final stimulation).Bronchoalveolar lavage fluid(BALF)and serum were harvested for analysis of concentrations of interleukin-4(IL-4),IL-13,immunoglobulin E and interferon-gamma(IFN-γ)by enzyme-linked immunosorbent assay.Pharmacology of airways and lung functions were also evaluated to identify the optimal group.RESULTS The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models.This effect is associated with decreased Th2 cytokines IL-4 and IL-13,and increased Th1 cytokine IFN-γ.The optimal dose of 2×105 cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4,IL-13,and IFN-γin serum and BALF compared to other single doses of HUC-MSC.Multiple treatments with the medium dose(2×105 cells)of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes.However,double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γproduction in serum or BALF more effectively than a single medium dose.CONCLUSION HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF,modulating airway remodeling and lung function.In this acute mouse asthma model,a single dosage of 2×105 is optimal,with more significant effects of decreasing airway obstruction requiring repeated administration.
文摘Radiation doses to patients in diagnostics and interventional radiology need to be optimized to comply with the principles of radiation protection in medical practice. This involves using specific detectors with respective diagnostic beams to carry out quality control/quality assurance tests needed to optimize patient doses in the hospital. Semiconductor detectors are used in dosimetry to verify the equipment performance and dose to patients. This work aims to assess the performance, energy dependence, and response of five commercially available semiconductor detectors in RQR, RQR-M, RQA, and RQT at Secondary Standard Dosimetry for clinical applications. The diagnostic beams were generated using Exradin A4 reference ion chamber and PTW electrometer. The ambient temperature and pressure were noted for KTP correction. The detectors designed for RQR showed good performance in RQT beams and vice versa. The detectors designed for RQR-M displayed high energy dependency in other diagnostic beams. The type of diagnostic beam quality determines the response of semiconductor detectors. Therefore, a detector should be calibrated according to the beam qualities to be measured.
文摘The radiation-sensitive field effect transistors(RADFET)radiation dosimeter is a type of radiation detector based on the total dose effects of the p-channel metal-oxide-semiconductor(PMOS)transistor.The RADFET chip was fabricated in United Microelectronics Center 8-inch process with a six-layer photomask.The chip including two identical PMOS transistors,occupies a size of 610μm×610μm.Each PMOS has a W/L ratio of 300μm/50μm,and a 400 nm thick gate oxide,which is formed by a dry-wet-dry oxygen process.The wet oxygen-formed gate oxide with more traps can capture more holes during irradiation,thus significantly changing the PMOS threshold voltage.Pre-irradiation measurement results from ten test chips show that the initial average voltage of the PMOS is 1.961 V with a dispersion of 5.7%.The irradiation experiment is conducted in a cobalt source facility with a dose rate of 50 rad(Si)/s.During irradiation,a constant current source circuit of 10μA was connected to monitoring the shift in threshold voltage under different total dose.When the total dose is 100 krad(Si),the shift in threshold voltage was approximately 1.37 V,which demonstrates that an excellent radiation function was achieved.
文摘A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a significant advancement in personalized radiotherapy by improving accuracy and reducing treatment-related toxicity.The model demonstrated strong predictive performance with R-values above 0.8,indicating its potential to improve treatment consistency.However,concerns arise from the small sample size and exclusion criteria,which may limit generalizability.Future studies should incorporate larger,more diverse patient cohorts,explore potential confounding factors such as tumor characteristics and delivery technique variability,and address the long-term effects of SBRT.
