Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological cond...Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systema...The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systematic review conducted by Sethi et al,published in the World Journal of Virology.The review critically examines the efficacy and safety of varying dosages of dexamethasone in severe COVID-19 patients,providing a comprehensive meta-analysis that underscores the current clinical recommendations favoring a low-dose regimen.Despite these findings,the review highlights the potential benefits of tailored dosages for specific patient subgroups,suggesting a need for personalized treatment approaches.This editorial expands on the implications of these findings,advocating for the integration of evolving clinical data into treatment protocols and calling for further research into patient-specific responses to therapy.It emphasizes the importance of adaptability and precision in pandemic response,urging the medical community to consider both the robustness of existing evidence and the potential for innovative approaches to enhance patient outcomes in the face of global health challenges.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
Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigati...Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.展开更多
Fluidized solidified soil(FSS)is an innovative backfill material that offers benefits such as easy pumping and straightforward construction.This study examined how varying the water-soil ratio and the curing agent dos...Fluidized solidified soil(FSS)is an innovative backfill material that offers benefits such as easy pumping and straightforward construction.This study examined how varying the water-soil ratio and the curing agent dosage affect the properties and microstructure of FSS.The strength development mechanism was investigated when composite solidification agents were used.The findings show that both the water-solid ratio and the curing agent dosage can affect the microstructure of FSS,thereby affecting its performance.When the water-solid ratio increases from 0.52 to 0.56,the unconfined compressive strength(UCS)and flexural strength of the FSS decrease by 34.1% and 39.3% after 28 d.Conversely,the curing agent dosage increasing from 10% to 30% will increase both UCS and flexural strength by 11.2 times and 11.1 times.As the curing age increases,the number of cracks at failure point in the FSS will increase and lead to a more complete failure.Numerous needle-like AFt,C-S-H gel,and C-(A)-S-H gel create a three-dimensional network by adhering to soil particles.展开更多
Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and...Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.展开更多
BACKGROUND The severe respiratory manifestations observed in severe coronavirus disease 2019(COVID-19)cases are often associated with an excessive inflammatory response.Dexamethasone,a synthetic glucocorticoid,exerts ...BACKGROUND The severe respiratory manifestations observed in severe coronavirus disease 2019(COVID-19)cases are often associated with an excessive inflammatory response.Dexamethasone,a synthetic glucocorticoid,exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells.This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases.Early on in the pandemic,the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support.However,the optimal dosage of corticosteroids remains debatable.Several studies that compare different doses of dexamethasone in COVID-19 exist,but the results are conflicting.AIM To review the latest evidence regarding dosage,safety,and efficacy of dexamethasone in severe COVID-19.METHODS We followed preferred reporting items for systematic reviews and meta-analysis guidelines.A detailed literature search was conducted across PubMed,Google Scholar,and Medline to include publications up to March 2024.Our keywords included“COVID-19”“SARS-CoV-2”“dexamethasone”“corticosteroid”“steroid”and“glucocorticoid”-along with their combinations.We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies.A meta-analysis was conducted using a random-effects model,assessing pooled odds ratios and mean differences,with heterogeneity gauged by the I2 statistic and theχ^(2) tests.RESULTS No statistical differences were found in 28-day all-cause mortality[pooled odds ratio(OR)=1.109,95%CI:0.918-1.340],60-day all-cause mortality(OR=0.873,95%CI:0.744-1.024;I2=47.29%),mean length of hospital stay(mean difference=-0.08 days,95%CI:-0.001 to 0.161)and adverse events(OR=0.877,95%CI:0.707-1.087).CONCLUSION Differing doses of corticosteroids have no clinical implications on mortality,mean length of hospital stay,and adverse events in COVID-19 patients.Additional research is required in patients requiring invasive or noninvasive ventilation.展开更多
Polyploidization in plants often leads to increased cell size and grain size,which may be affected by the increased genome dosage and transcription abundance.The synthesized Triticum durum(AABB)-Hay-naldia villosa(WM)...Polyploidization in plants often leads to increased cell size and grain size,which may be affected by the increased genome dosage and transcription abundance.The synthesized Triticum durum(AABB)-Hay-naldia villosa(WM)amphiploid(AABBM)has significantly increased grain size,especially grain length,than the tetraploid and diploid parents.To investigate how polyploidization affects grain development at the transcriptional level,we perform transcriptome analysis using the immature seeds of T.durum,H.villosa,and the amphiploid.The dosage effect genes are contributed more by differentially expressed genes from genome V of H.villosa.The dosage effect genes overrepresent grain development-related genes.Inter-estingly,the vernalization gene TaVRN1 is among the positive dosage effect genes in the T.durum-H.villosa and T.turgidum-Ae.tauschii amphiploids.The expression levels of TaVRN1 homologs are positively correlated with the grain size and weight.The TaVRN1-B1 or TaVRN1-D1 mutation shows delayed florescence,decreased cell size,grain size,and grain yield.These data indicate that dosage effect genes could be one of the important explanations for increased grain size by regulating grain development.The identification and functional validation of dosage effect genes may facilitate the finding of valuable genes for improvingwheat yield.展开更多
Copy number variations(CNVs)range in size from 50 base pairs(bp)to several megabases(Mb)and encompass various types of structural variations,such as insertions,deletions,duplications,and complex multiallelic events(Ma...Copy number variations(CNVs)range in size from 50 base pairs(bp)to several megabases(Mb)and encompass various types of structural variations,such as insertions,deletions,duplications,and complex multiallelic events(MacDonald et al.,2014).These genomic alterations modulate phenotype by altering gene dosage and transcriptional regulation,and are key drivers of biological evolution and determinants of genetic diversity and phenotypic variation.In recent years,CNVs have been detected in the genomes of various livestock species(Yuan et al.,2021;Chen et al.,2022).Upadhyay et al.(2017)conducted a comprehensive analysis of CNV distribution in the European cattle genome and determined that the Kit gene is associated with color-sidedness in English longhorn cattle.Another study presented extensive genome-wide information on CNVs in wild,commercial,and local chicken breeds to gain an integrated understanding of the domestication process and exclusively identified the genes involved(Chen et al.,2022).展开更多
To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].Howe...To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].展开更多
Cardiovascular disease remains the leading cause of mortality in women,yet it has not raised the awareness from the public.The pathogenesis of cardiovascular disease differs significantly between females and males con...Cardiovascular disease remains the leading cause of mortality in women,yet it has not raised the awareness from the public.The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones.Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects.Before menopause,cardiovascular protective effects of estrogens have been well described.Progestogens were often used in combination with estrogens in hormone therapy.Fluctuations in sex hormone levels,particularly estrogen deficiency,were considered the specific risk factor in women’s cardiovascular disease.However,considerable heterogeneity in the impact of hormone therapy was observed in clinical trials.The heterogeneity is likely closely associated with factors such as the initial time,administration route,dosage,and formulation of hormone therapy.This review will delve into the pathogenesis and hormone therapy,summarizing the effect of female sex hormones on hypertension,pre-eclampsia,coronary heart disease,heart failure with preserved ejection fraction,and cardiovascular risk factors specific to women.展开更多
This study investigates the efficacy of sodium alginate(SA),xanthan gum(XG),guar gum(GG)and chitosan(CS)d each applied at five different solid biopolymer-to-water mass ratios(or dosages)and cured for 7 d and 28 d d on...This study investigates the efficacy of sodium alginate(SA),xanthan gum(XG),guar gum(GG)and chitosan(CS)d each applied at five different solid biopolymer-to-water mass ratios(or dosages)and cured for 7 d and 28 d d on the unconfined compressive strength(UCS)performance of a high plasticity clayey soil.Moreover,on identifying the optimum biopolymer-treatment scenarios,their performance was compared against conventional stabilization using hydrated lime.For a given curing time,the UCS for all biopolymers followed a riseefall trend with increasing biopolymer dosage,peaking at an optimum dosage and then subsequently decreasing,such that all biopolymer-stabilized samples mobilized higher UCS values compared to the unamended soil.The optimum dosage was found to be 1.5%for SA,XG and CS,while a notably lower dosage of 0.5%was deemed optimum for GG.Similarly,for a given biopolymer type and dosage,increasing the curing time from 7 d to 28 d further enhanced the UCS,with the achieved improvements being generally more pronounced for XG-and CS-treated cases.None of the investigated biopolymers was able to produce UCS improvements equivalent to those obtained by the 28-d soilelime samples;however,the optimum XG,GG and CS dosages,particularly after 28 d of curing,were easily able to replicate 7-d lime stabilization outcomes achieved with as high as twice the soil’s lime demand.Finally,the fundamental principles of clay chemistry,in conjunction with the soil mechanics framework,were employed to identify and discuss the clayebiopolymer stabilization mechanisms.展开更多
The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within...The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.展开更多
Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndro...Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndromes.However,the selection and compatibility of herbs are complex and abstract due to intrinsic relationships between herbal properties and their overall functions.Network analysis is applied to demonstrate the complex relationships between individual herbal efficacy and the overall function of CM prescriptions.To illustrate their connections and correlations,prescription function(PF),prescription herb(PH),and herbal efficacy(HE)intranetworks are proposed based on CM theory to identify relationships between herbs and prescriptions.These three networks are then connected by PF-PH and PH-HE interlayer networks adopting herb dosage to form a multidimensional heterogeneous network,a Prescription-Herb-Function Network(PHFN).The network is applied to 112 classic prescriptions from Treatise on Exogenous Febrile and Miscellaneous Diseases to illustrate the application of PHFN.The PHFN is constructed including 146 functions in PF intra network,89 herbs in the PH intra network,and 163 herbal efficacies in the HE intra network.The results show that herb pairs with synergistic actions have stronger relevance,such as licorice-cassia twig,licorice-Chinese date,fresh ginger-Chinese date,etc.The integration of dosage to the network helps to indicate the main herbs for cluster analysis and automatic formulation.PHFN also reveals the internal relationships between the functions of prescriptions and composed herbal efficacies.展开更多
This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for typ...This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus(T2DM)patients with Hashimoto’s thyroiditis(HT)remains controversial.In the retrospective study we discuss herein,the authors highlighted significant improvements in thyroid function,thyroid antibodies,blood glucose,and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens,underscoring the value of these supplements.Our team is currently engaged in research exploring the relationship between micronutrients and HT,and we have obtained invaluable insights from the aforementioned study.Based on this research and current literature,we recommend a regimen of 4000 IU/day of vitamin D and 100-200μg/day of selenium for over three months to six months for patients with HT,particularly for those with concurrent T2DM.展开更多
The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cy...The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.展开更多
BACKGROUND Incidental pulmonary nodules are an increasingly common finding on computed tomography(CT)scans of the thorax due to the exponential rise in CT examin-ations in everyday practice.The majority of incidental ...BACKGROUND Incidental pulmonary nodules are an increasingly common finding on computed tomography(CT)scans of the thorax due to the exponential rise in CT examin-ations in everyday practice.The majority of incidental pulmonary nodules are benign and correctly identifying the small number of malignant nodules is cha-llenging.Ultra-low-dose CT(ULDCT)has been shown to be effective in diagnosis of respiratory pathology in comparison with traditional standard dose techniques.Our hypothesis was that ULDCT chest combined with model-based iterative reconstruction(MBIR)is comparable to standard dose CT(SDCT)chest in the analysis of pulmonary nodules with significant reduction in radiation dose.AIM To prospectively compare ULDCT chest combined with MBIR with SDCT chest in the analysis of solid pulmonary nodules.METHODS A prospective cohort study was conducted on adult patients(n=30)attending a respiratory medicine outpatient clinic in a tertiary referral university hospital for surveillance of previously detected indeterminate pulmonary nodules on SDCT chest.This study involved the acquisition of a reference SDCT chest followed immediately by an ULDCT chest.Nodule identification,nodule characterisation,nodule measurement,objective and subjective image quality and radiation dose were compared between ULDCT with MBIR and SDCT chest.RESULTS One hundred solid nodules were detected on ULDCT chest and 98 on SDCT chest.There was no significant difference in the characteristics of correctly identified nodules when comparing SDCT chest to ULDCT chest protocols.Signal-to-noise ratio was significantly increased in the ULDCT chest in all areas except in the paraspinal muscle at the maximum cardiac diameter level(P<0.001).The mean subjective image quality score for overall diagnostic acceptability was 8.9/10.The mean dose length product,computed tomography volume dose index and effective dose for the ULDCT chest protocol were 5.592 mGy.cm,0.16 mGy and 0.08 mSv respectively.These were significantly less than the SDCT chest protocol(P<0.001)and represent a radiation dose reduction of 97.6%.CONCLUSION ULDCT chest combined with MBIR is non-inferior to SDCT chest in the analysis of previously identified solid pulmonary nodules and facilitates a large reduction in radiation dose.展开更多
BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication ...BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.展开更多
Setting: Provincial General Reference Hospital of Bukavu, General Reference Hospital of Panzi, General Reference Hospital of Ciriri, General Reference Hospital of Nyatende and Biopharm Hospital Center. Objective: Cont...Setting: Provincial General Reference Hospital of Bukavu, General Reference Hospital of Panzi, General Reference Hospital of Ciriri, General Reference Hospital of Nyatende and Biopharm Hospital Center. Objective: Contribute to the improvement of the anesthetic ECP of patients benefiting from MVA for incomplete abortion, Describe the methodology used for adoption of the dosage formula in Anesthesia for MVA, present the mathematical demonstration leading to the dosage formula in anesthesia for MVA. Materials and Methods: Our study was descriptive by mathematical demonstration of obtaining the equilibrium constant of the dosage formula of bipuvacaine 0.1% and Fentanyl 50 µg% adapted to the weight and specific size of patients treated anesthetically in MVA cases for incomplete abortion. We also carried out an operational research by first determining the interval where our equilibrium constant is included and secondly by means of the ends of the intervals found correlated to the ends of intervals of possible weights and sizes in the being normal human female of childbearing age to arrive at the real numerical value of the equilibrium constant of the BUKAVU Dosage Formula in the case of anesthesia for MVA during the management of incomplete abortions. Results: TWO-STAGE OPERATIONAL RESEARCH: • Determination of the interval where the equilibrium constant x = −0.95 x x by crossing the means between the extremes of volumes of anesthetic drugs giving a satisfactory sensory block without hemodynamic disturbance and the extremes of normal weight and height for women of childbearing age. We ended up with X = 0.37. Conclusion: At the end of our study which had the general objectives of contributing to the improvement of the anesthetic PEC of patients receiving MVA for incomplete abortion and specific objectives of describing the methodology used for adoption of the dosage formula in Anesthesia for MVA and present the mathematical demonstration which resulted in the dosage formula in nesthesia for MVA, it appears that the dosage formula of Bukavu, in case of intrathecal spinal analgesia of MVA for incomplete abortion provides precision on the specificity of the doses of bipuvacaine hypobarre 0.1% and Fentanyl 50 µg% reported to each patient according to her weight and height. Its application could therefore reduce morbidity and mortality and improve patient-practitioner comfort in the event of MVA for incomplete abortion following the dosage precision it provides.展开更多
基金supported by Fonds Clinatec and COVEA France(to JM).
文摘Neurons are notoriously vulnerable cell types.Even the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper function.In most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell death.The challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological conditions.Such interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical levels.In this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective treatments.These are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systematic review conducted by Sethi et al,published in the World Journal of Virology.The review critically examines the efficacy and safety of varying dosages of dexamethasone in severe COVID-19 patients,providing a comprehensive meta-analysis that underscores the current clinical recommendations favoring a low-dose regimen.Despite these findings,the review highlights the potential benefits of tailored dosages for specific patient subgroups,suggesting a need for personalized treatment approaches.This editorial expands on the implications of these findings,advocating for the integration of evolving clinical data into treatment protocols and calling for further research into patient-specific responses to therapy.It emphasizes the importance of adaptability and precision in pandemic response,urging the medical community to consider both the robustness of existing evidence and the potential for innovative approaches to enhance patient outcomes in the face of global health challenges.
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.
基金National Research Fund of South Africa(grant number:137792).
文摘Background:Cannabidiol(CBD)has numerous therapeutic properties,and is used to treat neurological conditions,such as neuroinflammation.However,the optimal dose of CBD to penetrate the brain requires further investigation.The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain.The secondary aim was to determine whether sex is a confounding factor.Methods:Thirty adult Kramnik mice,divided equally into three groups,were ad-ministered CBD oil intrabuccally at three doses-10,20,and 30 mg/kg,euthanized 6 h later,and whole brain,urine,and blood samples were collected.Liquid chro-matography with tandem mass spectrometry was used to analyze the collected samples.Results:CBD and its three metabolites—7-carboxy cannabidiol(7-COOH-CBD),7-hydroxy cannabidiol(7-OH-CBD)and 6-hydroxy cannabidiol(6-OH-CBD),were identified and quantified in all samples.The 10 and 20 mg/kg doses of CBD produced similar results in the brain,but the group given the 10 mg/kg dose had the least vari-ation.The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples,but also the greatest variation.Sex only became a confounding factor at 30 mg/kg.Conclusions:This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples,with the least variation among the doses,and sex was not a confounder at 10 mg/kg.
基金Funded by the China Construction Shares Technology Research and Development Project(No.CSCEC-2023-Z-07)CSCEC Strait Major Scientific and Technological Project(No.ZJHX2023C001)+1 种基金Engineering Research Center of Prevention and Control of Geological Disasters in the Mountainous Areas of Northern Fujian,Fujian Province University,China(No.WYERC2024-3)Science s of Fujian Province(No.2023J01476)。
文摘Fluidized solidified soil(FSS)is an innovative backfill material that offers benefits such as easy pumping and straightforward construction.This study examined how varying the water-soil ratio and the curing agent dosage affect the properties and microstructure of FSS.The strength development mechanism was investigated when composite solidification agents were used.The findings show that both the water-solid ratio and the curing agent dosage can affect the microstructure of FSS,thereby affecting its performance.When the water-solid ratio increases from 0.52 to 0.56,the unconfined compressive strength(UCS)and flexural strength of the FSS decrease by 34.1% and 39.3% after 28 d.Conversely,the curing agent dosage increasing from 10% to 30% will increase both UCS and flexural strength by 11.2 times and 11.1 times.As the curing age increases,the number of cracks at failure point in the FSS will increase and lead to a more complete failure.Numerous needle-like AFt,C-S-H gel,and C-(A)-S-H gel create a three-dimensional network by adhering to soil particles.
基金supported by Postdoctoral Innovation Talents’ Support Programthe National Natural Science Foundation of China (32130099)+1 种基金the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-CXRC-038)Laboratory of Lingnan Modern Agriculture Project (NT2021005)。
文摘Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.
文摘BACKGROUND The severe respiratory manifestations observed in severe coronavirus disease 2019(COVID-19)cases are often associated with an excessive inflammatory response.Dexamethasone,a synthetic glucocorticoid,exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells.This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases.Early on in the pandemic,the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support.However,the optimal dosage of corticosteroids remains debatable.Several studies that compare different doses of dexamethasone in COVID-19 exist,but the results are conflicting.AIM To review the latest evidence regarding dosage,safety,and efficacy of dexamethasone in severe COVID-19.METHODS We followed preferred reporting items for systematic reviews and meta-analysis guidelines.A detailed literature search was conducted across PubMed,Google Scholar,and Medline to include publications up to March 2024.Our keywords included“COVID-19”“SARS-CoV-2”“dexamethasone”“corticosteroid”“steroid”and“glucocorticoid”-along with their combinations.We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies.A meta-analysis was conducted using a random-effects model,assessing pooled odds ratios and mean differences,with heterogeneity gauged by the I2 statistic and theχ^(2) tests.RESULTS No statistical differences were found in 28-day all-cause mortality[pooled odds ratio(OR)=1.109,95%CI:0.918-1.340],60-day all-cause mortality(OR=0.873,95%CI:0.744-1.024;I2=47.29%),mean length of hospital stay(mean difference=-0.08 days,95%CI:-0.001 to 0.161)and adverse events(OR=0.877,95%CI:0.707-1.087).CONCLUSION Differing doses of corticosteroids have no clinical implications on mortality,mean length of hospital stay,and adverse events in COVID-19 patients.Additional research is required in patients requiring invasive or noninvasive ventilation.
基金This work was financially supported by the National Key Research and Development Program of China(Grant No.2022YFF1002900 and 2020YFE0202900)the National Natural Science Foundation of China(32270576)+4 种基金Jiangsu Provincial Key Research and Development Program(BE2022346)Seed Industry Revitalization Project of Jiangsu Province(JBGS[2021]006 and JBGS[2021]013)the Jiangsu Agricultural Technology System(JATS[2023]422)the Joint Research of Wheat Variety Improvement of AnhuiZhongshan Biological Breeding Laboratory(ZSBBL)(ZSBBL-KY2023-02-2)。
文摘Polyploidization in plants often leads to increased cell size and grain size,which may be affected by the increased genome dosage and transcription abundance.The synthesized Triticum durum(AABB)-Hay-naldia villosa(WM)amphiploid(AABBM)has significantly increased grain size,especially grain length,than the tetraploid and diploid parents.To investigate how polyploidization affects grain development at the transcriptional level,we perform transcriptome analysis using the immature seeds of T.durum,H.villosa,and the amphiploid.The dosage effect genes are contributed more by differentially expressed genes from genome V of H.villosa.The dosage effect genes overrepresent grain development-related genes.Inter-estingly,the vernalization gene TaVRN1 is among the positive dosage effect genes in the T.durum-H.villosa and T.turgidum-Ae.tauschii amphiploids.The expression levels of TaVRN1 homologs are positively correlated with the grain size and weight.The TaVRN1-B1 or TaVRN1-D1 mutation shows delayed florescence,decreased cell size,grain size,and grain yield.These data indicate that dosage effect genes could be one of the important explanations for increased grain size by regulating grain development.The identification and functional validation of dosage effect genes may facilitate the finding of valuable genes for improvingwheat yield.
基金the National Natural Science Foundation of China(No.32272851)the China Agriculture Research System of MOF and MARA(No.CARS-38)。
文摘Copy number variations(CNVs)range in size from 50 base pairs(bp)to several megabases(Mb)and encompass various types of structural variations,such as insertions,deletions,duplications,and complex multiallelic events(MacDonald et al.,2014).These genomic alterations modulate phenotype by altering gene dosage and transcriptional regulation,and are key drivers of biological evolution and determinants of genetic diversity and phenotypic variation.In recent years,CNVs have been detected in the genomes of various livestock species(Yuan et al.,2021;Chen et al.,2022).Upadhyay et al.(2017)conducted a comprehensive analysis of CNV distribution in the European cattle genome and determined that the Kit gene is associated with color-sidedness in English longhorn cattle.Another study presented extensive genome-wide information on CNVs in wild,commercial,and local chicken breeds to gain an integrated understanding of the domestication process and exclusively identified the genes involved(Chen et al.,2022).
基金The study was supported by grants from the National Natural Science Foundation of China(81871259,81971495,82070675,81530048,82200731 and 81570562)the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,and the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].
基金supported by the National Key Research and Development Program of China (No.2022YFC-3602500)
文摘Cardiovascular disease remains the leading cause of mortality in women,yet it has not raised the awareness from the public.The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones.Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects.Before menopause,cardiovascular protective effects of estrogens have been well described.Progestogens were often used in combination with estrogens in hormone therapy.Fluctuations in sex hormone levels,particularly estrogen deficiency,were considered the specific risk factor in women’s cardiovascular disease.However,considerable heterogeneity in the impact of hormone therapy was observed in clinical trials.The heterogeneity is likely closely associated with factors such as the initial time,administration route,dosage,and formulation of hormone therapy.This review will delve into the pathogenesis and hormone therapy,summarizing the effect of female sex hormones on hypertension,pre-eclampsia,coronary heart disease,heart failure with preserved ejection fraction,and cardiovascular risk factors specific to women.
基金supported by an Australian Government Research Training Program(RTP)scholarship.
文摘This study investigates the efficacy of sodium alginate(SA),xanthan gum(XG),guar gum(GG)and chitosan(CS)d each applied at five different solid biopolymer-to-water mass ratios(or dosages)and cured for 7 d and 28 d d on the unconfined compressive strength(UCS)performance of a high plasticity clayey soil.Moreover,on identifying the optimum biopolymer-treatment scenarios,their performance was compared against conventional stabilization using hydrated lime.For a given curing time,the UCS for all biopolymers followed a riseefall trend with increasing biopolymer dosage,peaking at an optimum dosage and then subsequently decreasing,such that all biopolymer-stabilized samples mobilized higher UCS values compared to the unamended soil.The optimum dosage was found to be 1.5%for SA,XG and CS,while a notably lower dosage of 0.5%was deemed optimum for GG.Similarly,for a given biopolymer type and dosage,increasing the curing time from 7 d to 28 d further enhanced the UCS,with the achieved improvements being generally more pronounced for XG-and CS-treated cases.None of the investigated biopolymers was able to produce UCS improvements equivalent to those obtained by the 28-d soilelime samples;however,the optimum XG,GG and CS dosages,particularly after 28 d of curing,were easily able to replicate 7-d lime stabilization outcomes achieved with as high as twice the soil’s lime demand.Finally,the fundamental principles of clay chemistry,in conjunction with the soil mechanics framework,were employed to identify and discuss the clayebiopolymer stabilization mechanisms.
基金Supported by the Project of Special Funds for Science and Technology Cooperation in Guizhou Provinces and Zunyi City,No.Shengshikehe(2015)53.
文摘The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.
文摘Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndromes.However,the selection and compatibility of herbs are complex and abstract due to intrinsic relationships between herbal properties and their overall functions.Network analysis is applied to demonstrate the complex relationships between individual herbal efficacy and the overall function of CM prescriptions.To illustrate their connections and correlations,prescription function(PF),prescription herb(PH),and herbal efficacy(HE)intranetworks are proposed based on CM theory to identify relationships between herbs and prescriptions.These three networks are then connected by PF-PH and PH-HE interlayer networks adopting herb dosage to form a multidimensional heterogeneous network,a Prescription-Herb-Function Network(PHFN).The network is applied to 112 classic prescriptions from Treatise on Exogenous Febrile and Miscellaneous Diseases to illustrate the application of PHFN.The PHFN is constructed including 146 functions in PF intra network,89 herbs in the PH intra network,and 163 herbal efficacies in the HE intra network.The results show that herb pairs with synergistic actions have stronger relevance,such as licorice-cassia twig,licorice-Chinese date,fresh ginger-Chinese date,etc.The integration of dosage to the network helps to indicate the main herbs for cluster analysis and automatic formulation.PHFN also reveals the internal relationships between the functions of prescriptions and composed herbal efficacies.
基金Supported by the Discipline Construction Project of Hunan University of Chinese Medicine,No.22JBZ002.
文摘This letter discusses the publication by Feng et al.Iodine,selenium,and vitamin D are closely associated with thyroid hormone production in humans;however,the efficacy of selenium and vitamin D supplementation for type 2 diabetes mellitus(T2DM)patients with Hashimoto’s thyroiditis(HT)remains controversial.In the retrospective study we discuss herein,the authors highlighted significant improvements in thyroid function,thyroid antibodies,blood glucose,and blood lipid in T2DM patients with HT following addition of vitamin D and selenium to their antidiabetic regimens,underscoring the value of these supplements.Our team is currently engaged in research exploring the relationship between micronutrients and HT,and we have obtained invaluable insights from the aforementioned study.Based on this research and current literature,we recommend a regimen of 4000 IU/day of vitamin D and 100-200μg/day of selenium for over three months to six months for patients with HT,particularly for those with concurrent T2DM.
基金Hainan Province Major Science and Technology Plan Projects(No.ZDKJ2021037,ZDKJ2017007)National Natural Science Foundation of China(No.81960283),and Co-funded by the Hainan Provincial Academician Innovation Platform Research Project and the Hainan Provincial Clinical Medicine Center Construction Project。
文摘The gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as an efficacious alternative to the GnRH agonist protocol for controlled ovarian hyperstimulation (COH) during in vitro fertilization (IVF) cycles, and has been demonstrated applicability in infertile female patients with diverse ovarian responses. While the clinical implementation of the antagonist COH protocol has achieved widespread consensus, opportunities for refinement persist. Therefore, this review article focuses on the advantages and disadvantages of GnRH antagonist protocol, the selection of optimal standard doses, and the strategies for adjusting antagonist doses after the premature luteinizing hormone (LH) surge, aiming to provide more reasonable and scientific recommendations for the application of this scheme.
文摘BACKGROUND Incidental pulmonary nodules are an increasingly common finding on computed tomography(CT)scans of the thorax due to the exponential rise in CT examin-ations in everyday practice.The majority of incidental pulmonary nodules are benign and correctly identifying the small number of malignant nodules is cha-llenging.Ultra-low-dose CT(ULDCT)has been shown to be effective in diagnosis of respiratory pathology in comparison with traditional standard dose techniques.Our hypothesis was that ULDCT chest combined with model-based iterative reconstruction(MBIR)is comparable to standard dose CT(SDCT)chest in the analysis of pulmonary nodules with significant reduction in radiation dose.AIM To prospectively compare ULDCT chest combined with MBIR with SDCT chest in the analysis of solid pulmonary nodules.METHODS A prospective cohort study was conducted on adult patients(n=30)attending a respiratory medicine outpatient clinic in a tertiary referral university hospital for surveillance of previously detected indeterminate pulmonary nodules on SDCT chest.This study involved the acquisition of a reference SDCT chest followed immediately by an ULDCT chest.Nodule identification,nodule characterisation,nodule measurement,objective and subjective image quality and radiation dose were compared between ULDCT with MBIR and SDCT chest.RESULTS One hundred solid nodules were detected on ULDCT chest and 98 on SDCT chest.There was no significant difference in the characteristics of correctly identified nodules when comparing SDCT chest to ULDCT chest protocols.Signal-to-noise ratio was significantly increased in the ULDCT chest in all areas except in the paraspinal muscle at the maximum cardiac diameter level(P<0.001).The mean subjective image quality score for overall diagnostic acceptability was 8.9/10.The mean dose length product,computed tomography volume dose index and effective dose for the ULDCT chest protocol were 5.592 mGy.cm,0.16 mGy and 0.08 mSv respectively.These were significantly less than the SDCT chest protocol(P<0.001)and represent a radiation dose reduction of 97.6%.CONCLUSION ULDCT chest combined with MBIR is non-inferior to SDCT chest in the analysis of previously identified solid pulmonary nodules and facilitates a large reduction in radiation dose.
文摘BACKGROUND Medication errors,especially in dosage calculation,pose risks in healthcare.Artificial intelligence(AI)systems like ChatGPT and Google Bard may help reduce errors,but their accuracy in providing medication information remains to be evaluated.AIM To evaluate the accuracy of AI systems(ChatGPT 3.5,ChatGPT 4,Google Bard)in providing drug dosage information per Harrison's Principles of Internal Medicine.METHODS A set of natural language queries mimicking real-world medical dosage inquiries was presented to the AI systems.Responses were analyzed using a 3-point Likert scale.The analysis,conducted with Python and its libraries,focused on basic statistics,overall system accuracy,and disease-specific and organ system accuracies.RESULTS ChatGPT 4 outperformed the other systems,showing the highest rate of correct responses(83.77%)and the best overall weighted accuracy(0.6775).Disease-specific accuracy varied notably across systems,with some diseases being accurately recognized,while others demonstrated significant discrepancies.Organ system accuracy also showed variable results,underscoring system-specific strengths and weaknesses.CONCLUSION ChatGPT 4 demonstrates superior reliability in medical dosage information,yet variations across diseases emphasize the need for ongoing improvements.These results highlight AI's potential in aiding healthcare professionals,urging continuous development for dependable accuracy in critical medical situations.
文摘Setting: Provincial General Reference Hospital of Bukavu, General Reference Hospital of Panzi, General Reference Hospital of Ciriri, General Reference Hospital of Nyatende and Biopharm Hospital Center. Objective: Contribute to the improvement of the anesthetic ECP of patients benefiting from MVA for incomplete abortion, Describe the methodology used for adoption of the dosage formula in Anesthesia for MVA, present the mathematical demonstration leading to the dosage formula in anesthesia for MVA. Materials and Methods: Our study was descriptive by mathematical demonstration of obtaining the equilibrium constant of the dosage formula of bipuvacaine 0.1% and Fentanyl 50 µg% adapted to the weight and specific size of patients treated anesthetically in MVA cases for incomplete abortion. We also carried out an operational research by first determining the interval where our equilibrium constant is included and secondly by means of the ends of the intervals found correlated to the ends of intervals of possible weights and sizes in the being normal human female of childbearing age to arrive at the real numerical value of the equilibrium constant of the BUKAVU Dosage Formula in the case of anesthesia for MVA during the management of incomplete abortions. Results: TWO-STAGE OPERATIONAL RESEARCH: • Determination of the interval where the equilibrium constant x = −0.95 x x by crossing the means between the extremes of volumes of anesthetic drugs giving a satisfactory sensory block without hemodynamic disturbance and the extremes of normal weight and height for women of childbearing age. We ended up with X = 0.37. Conclusion: At the end of our study which had the general objectives of contributing to the improvement of the anesthetic PEC of patients receiving MVA for incomplete abortion and specific objectives of describing the methodology used for adoption of the dosage formula in Anesthesia for MVA and present the mathematical demonstration which resulted in the dosage formula in nesthesia for MVA, it appears that the dosage formula of Bukavu, in case of intrathecal spinal analgesia of MVA for incomplete abortion provides precision on the specificity of the doses of bipuvacaine hypobarre 0.1% and Fentanyl 50 µg% reported to each patient according to her weight and height. Its application could therefore reduce morbidity and mortality and improve patient-practitioner comfort in the event of MVA for incomplete abortion following the dosage precision it provides.
