Objective: The rapid detection of blood stream infection has the potential to not only improve patient outcomes due to quicker administration of appropriate antibiotics but also improve antibiotic stewardship by reduc...Objective: The rapid detection of blood stream infection has the potential to not only improve patient outcomes due to quicker administration of appropriate antibiotics but also improve antibiotic stewardship by reducing patient exposures to ineffective or unnecessary broad-spectrum antibiotics. Methods: In this study blood samples from acute leukemia neutropenic patients (samples under study) and non neutropenic patients (control) were tested using cultural and non-cultural based techniques via blood culture, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and Molecular techniques (bacterial 16S rDNA analysis). Results: About 22% & 15% were shown positive in blood culturing;94% & 85% were positive for CRP;86% and 75% were presented by elevation in ESR rate for the first hour;94% and 80% were presented by elevation in ESR rate for second hour. Treatment response of the positive cases by blood culture only was found to be 72.7% and 100% not in remission for samples under study and control respectively. In cases under study there is statistically significant correlation between culture growth sensitivity and PCR technique with P value 0.005.展开更多
Objective: To study the differences in serum inflammatory mediators in early blood culture positive and negative patients with bacterial bloodstream infection. Methods: Patients who were hospitalized due to suspected ...Objective: To study the differences in serum inflammatory mediators in early blood culture positive and negative patients with bacterial bloodstream infection. Methods: Patients who were hospitalized due to suspected bacterial bloodstream infection between December 2015 and September 2017 were divided into positive group and negative group according to the results of blood culture, and healthy volunteers who underwent medical examination during the same period were selected as control group. Peripheral blood specimens were collected from patients with suspected bacteremia on admission, the peripheral blood specimens were collected from the control group of volunteers during physical examination, and the levels of pro-inflammatory cytokines, anti-inflammatory cytokines, adhesion factors and chemokines were determined. Results: Serum PCT, CRP, IL-6, IL-17, IL-23, IL-4, IL-10, IL-13, sTM, ICAM-1, VCAM-1, EOTAXIN-3 and MCP-1 levels of positive group and negative group were significantly higher than those of control group, and serum PCT, CRP, IL-6, IL-17, IL-23, IL-4, IL-10, IL-13, sTM, ICAM-1, VCAM-1, EOTAXIN-3 and MCP-1 levels of positive group were significantly higher than those of negative group. Conclusions: Detection of serum inflammatory mediators can early predict the bacterial bloodstream infection.展开更多
After newborn screening is completed, most states retain leftover dried bloodspots. These dried bloodspots are stored for varying lengths of time among different state newborn screening programs. Dried bloodspots are ...After newborn screening is completed, most states retain leftover dried bloodspots. These dried bloodspots are stored for varying lengths of time among different state newborn screening programs. Dried bloodspots are a unique and valuable resource for the development of new newborn screening tests, quality assurance and biomedical research. Recent changes to the 2014 Newborn Screening Reauthorization Saves Lives Act require explicit parental consent for the retention and use of dried bloodspots in federally funded research. This has raised several ethical and regulatory issues and highlighted the challenges of respecting individual autonomy and public health goals. This article provides an overview of these issues and discusses methods for obtaining parental consent. These issues may be applicable to consent for the storage and use of biospecimens among other settings according to proposed changes to the Common Rule.展开更多
Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of...Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.展开更多
Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizoph...Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.展开更多
Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compen...Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.展开更多
Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise.Since this technology has been growing and is now succes...Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise.Since this technology has been growing and is now successfully used in laboratory and sports settings,this systematic review aimed to synthesize the evidence and enhance an integrative understanding of bloodflow adjustments and oxygen(O_(2))changes(i.e.,the balance between O_(2) delivery and O_(2) consumption)within the cerebral and muscle systems during exercise.Methods:A systematic review was conducted using PubMed,Embase,Scopus,and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise.This review considered manuscripts written in English and available before February 9,2023.Each step of screening involved evaluation by 2 inde-pendent authors,with disagreements resolved by a third author.The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.Results:Twenty studies were included,of which 80%had good methodological quality,and involved 290 young or middle-aged adults.Different types of exercises were used to assess cerebral and muscle hemodynamic changes,such as cycling(n=11),treadmill(n=1),knee extension(n=5),isometric contraction of biceps brachii(n=3),and duet swim routines(n=1).The cerebral hemodynamics anal-ysis was focused on the frontal cortex(n=20),while in the muscle,the analysis involved vastus lateralis(n=18),gastrocnemius(n=3),biceps brachii(n=5),deltoid(n=1),and intercostal muscle(n=1).Overall,muscle deoxygenation increases during exercise,reaching a plateau in voluntary exhaustion,while in the brain,oxyhemoglobin concentration increases with exercise intensity,reaching a plateau or declining at the exhaustion point.Conclusion:Muscle and cerebral oxygenation respond differently to exercise,with muscle increasing O_(2) utilization and cerebral tissue increasing O_(2) delivery during exercise.However,at the exhaustion point,both muscle and cerebral oxygenation become compromised.This is characterized by a reduction in bloodflow and a decrease in O_(2) extraction in the muscle,while in the brain,oxygenation reaches a plateau or decline,potentially resulting in motor failure during exercise.展开更多
The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervo...The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.展开更多
Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinica...Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully controlled.However,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical applications.To this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation.Different from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional properties.This may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.展开更多
Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body w...Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.展开更多
Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid no...Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD...Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.展开更多
Monitoring blood pressure is a critical aspect of safeguarding an individual’s health,as early detection of abnormal blood pressure levels facilitates timely medical intervention,ultimately leading to a reduction in ...Monitoring blood pressure is a critical aspect of safeguarding an individual’s health,as early detection of abnormal blood pressure levels facilitates timely medical intervention,ultimately leading to a reduction in mortality rates associated with cardiovascular diseases.Consequently,the development of a robust and continuous blood pressure monitoring system holds paramount significance.In the context of this research paper,we introduce an innovative deep learning regression model that harnesses phonocardiogram(PCG)data to achieve precise blood pressure estimation.Our novel approach incorporates a convolutional neural network(CNN)-based regression model,which not only enhances its adaptability to spatial variations but also empowers it to capture intricate patterns within the PCG signals.These advancements contribute significantly to the overall accuracy of blood pressure estimation.To substantiate the effectiveness of our proposed method,we meticulously gathered PCG signal data from 78 volunteers,adhering to the ethical guidelines of Suranaree University of Technology(Human Research Ethics number EC-65-78).Subsequently,we rigorously preprocessed the dataset to ensure its integrity.We further employed a K-fold cross-validation procedure for data division and alignment,combining the resulting datasets with a CNNfor blood pressure estimation.The experimental results are highly promising,yielding aMeanAbsolute Error(MAE)and standard deviation(STD)of approximately 10.69±7.23 mmHg for systolic pressure and 6.89±5.22 mmHg for diastolic pressure.Our study underscores the potential for precise blood pressure estimation,particularly using PCG signals,paving the way for a practical,non-invasive method with broad applicability in the healthcare domain.Early detection of abnormal blood pressure levels can facilitate timely medical interventions,ultimately reducing cardiovascular disease-related mortality rates.展开更多
BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to deco...BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.展开更多
Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control gr...Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.展开更多
Dietary parboiled rice(PR)has a low risk of disease,but little is known about the contribution of PR to the prevention of hyperlipidemia.The potential role and underlying mechanisms of PR in hyperlipidemia were evalua...Dietary parboiled rice(PR)has a low risk of disease,but little is known about the contribution of PR to the prevention of hyperlipidemia.The potential role and underlying mechanisms of PR in hyperlipidemia were evaluated in this study.Male C57BL/6J mice were fed with a normal diet,high-fat diet(HFD)containing refined rice(HFDRR)or PR(HFDPR).It was found that PR intervention improved lipid accumulation in mice.Transcriptomic data analysis revealed that 27 genes were up-regulated(mostly involved in lipid breakdown)and 86 genes were down-regulated(mostly involved in inflammatory responses)in the HFDPR group compared to the HFDRR group.And 15 differentially expressed genes(DEGs)were validated by quantitative real-time PCR(RT-qPCR),while protein interaction network showed that protein tyrosine phosphatase receptor type C(PTPRC)has a central role.The gut microbiota of mice was also altered after different dietary treatments,with higher ratio of Firmicutes and Bacteroidetes,increased abundances of Ruminococcaceae,Lachnospiraceae,Christensenellaceae,Porphyromonadaceae,Rikenellaceae and Prevotellaceae,and decreased abundances of Lactobacillaceae,Peptostreptococcaceae,Erysipelotrichaceae and Actinobacteria in the HFDRR group.In addition,it was observed that PPAR signaling pathway may act as a bridge between DEGs and differential gut microbiota.These results suggested that PR can prevent hyperlipidemia by modulating liver genes and gut microbiota.展开更多
Objective:This study aimed to identify predictive factors for percutaneous nephrolithotomy(PCNL)bleeding risks.With better risk stratification,bleeding in high-risk patient can be anticipated and facilitates early ide...Objective:This study aimed to identify predictive factors for percutaneous nephrolithotomy(PCNL)bleeding risks.With better risk stratification,bleeding in high-risk patient can be anticipated and facilitates early identification.Methods:A prospective observational study of PCNL performed at our institution was done.All adults with radio-opaque renal stones planned for PCNL were included except those with coagulopathy,planned for additional procedures.Factors including gender,co-morbidities,body mass index,stone burden,puncture site,tract dilatation size,operative position,surgeon's seniority,and operative duration were studied using stepwise multivariate regression analysis to identify the predictive factors associated with higher estimated hemoglobin(Hb)deficiency.Results:Overall,4.86%patients(n=7)received packed cells transfusion.The mean estimated Hb deficiency was 1.3(range 0-6.5)g/dL and the median was 1.0 g/dL.Stepwise multivariate regression analysis revealed that absence of hypertension(p=0.024),puncture site(p=0.027),and operative duration(p=0.023)were significantly associated with higher estimated Hb deficiency.However,the effect sizes are rather small with partial eta-squared of 0.037,0.066,and 0.038,respectively.Observed power obtained was 0.621,0.722,and 0.625,respectively.Other factors studied did not correlate with Hb difference.Conclusion:Hypertension,puncture site,and operative duration have significant impact on estimated Hb deficiency during PCNL.However,the effect size is rather small despite adequate study power obtained.Nonetheless,operative position(supine or prone),puncture number,or tract dilatation size did not correlate with Hb difference.The mainstay of reducing bleeding in PCNL is still meticulous operative technique.Our study findings also suggest that PCNL can be safely done by urology trainees under supervision in suitably selected patient,without increasing risk of bleeding.展开更多
文摘Objective: The rapid detection of blood stream infection has the potential to not only improve patient outcomes due to quicker administration of appropriate antibiotics but also improve antibiotic stewardship by reducing patient exposures to ineffective or unnecessary broad-spectrum antibiotics. Methods: In this study blood samples from acute leukemia neutropenic patients (samples under study) and non neutropenic patients (control) were tested using cultural and non-cultural based techniques via blood culture, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and Molecular techniques (bacterial 16S rDNA analysis). Results: About 22% & 15% were shown positive in blood culturing;94% & 85% were positive for CRP;86% and 75% were presented by elevation in ESR rate for the first hour;94% and 80% were presented by elevation in ESR rate for second hour. Treatment response of the positive cases by blood culture only was found to be 72.7% and 100% not in remission for samples under study and control respectively. In cases under study there is statistically significant correlation between culture growth sensitivity and PCR technique with P value 0.005.
文摘Objective: To study the differences in serum inflammatory mediators in early blood culture positive and negative patients with bacterial bloodstream infection. Methods: Patients who were hospitalized due to suspected bacterial bloodstream infection between December 2015 and September 2017 were divided into positive group and negative group according to the results of blood culture, and healthy volunteers who underwent medical examination during the same period were selected as control group. Peripheral blood specimens were collected from patients with suspected bacteremia on admission, the peripheral blood specimens were collected from the control group of volunteers during physical examination, and the levels of pro-inflammatory cytokines, anti-inflammatory cytokines, adhesion factors and chemokines were determined. Results: Serum PCT, CRP, IL-6, IL-17, IL-23, IL-4, IL-10, IL-13, sTM, ICAM-1, VCAM-1, EOTAXIN-3 and MCP-1 levels of positive group and negative group were significantly higher than those of control group, and serum PCT, CRP, IL-6, IL-17, IL-23, IL-4, IL-10, IL-13, sTM, ICAM-1, VCAM-1, EOTAXIN-3 and MCP-1 levels of positive group were significantly higher than those of negative group. Conclusions: Detection of serum inflammatory mediators can early predict the bacterial bloodstream infection.
文摘After newborn screening is completed, most states retain leftover dried bloodspots. These dried bloodspots are stored for varying lengths of time among different state newborn screening programs. Dried bloodspots are a unique and valuable resource for the development of new newborn screening tests, quality assurance and biomedical research. Recent changes to the 2014 Newborn Screening Reauthorization Saves Lives Act require explicit parental consent for the retention and use of dried bloodspots in federally funded research. This has raised several ethical and regulatory issues and highlighted the challenges of respecting individual autonomy and public health goals. This article provides an overview of these issues and discusses methods for obtaining parental consent. These issues may be applicable to consent for the storage and use of biospecimens among other settings according to proposed changes to the Common Rule.
文摘Inappropriate levels of hyperactivity,impulsivity,and inattention characterize attention deficit hyperactivity disorder,a common childhood-onset neuropsychiatric disorder.The cognitive function and learning ability of children with attention deficit hyperactivity disorder are affected,and these symptoms may persist to adulthood if they are not treated.The diagnosis of attention deficit hyperactivity disorder is only based on symptoms and objective tests for attention deficit hyperactivity disorder are missing.Treatments for attention deficit hyperactivity disorder in children include medications,behavior therapy,counseling,and education services which can relieve many of the symptoms of attention deficit hyperactivity disorder but cannot cure it.There is a need for a molecular biomarker to distinguish attention deficit hyperactivity disorder from healthy subjects and other neurological conditions,which would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of attention deficit hyperactivity disorder.The recent studies reviewed had performed microRNA profiling in whole blood,white blood cells,blood plasma,and blood serum of children with attention deficit hyperactivity disorder.A large number of microRNAs were dysregulated when compared to healthy controls and with some overlap between individual studies.From the studies that had included a validation set of patients and controls,potential candidate biomarkers for attention deficit hyperactivity disorder in children could be miR-140-3p,let-7g-5p,-30e-5p,-223-3p,-142-5p,-486-5p,-151a-3p,-151a-5p,and-126-5p in total white blood cells,and miR-4516,-6090,-4763-3p,-4281,-4466,-101-3p,-130a-3p,-138-5p,-195-5p,and-106b-5p in blood serum.Further studies are warranted with children and adults with attention deficit hyperactivity disorder,and consideration should be given to utilizing rat models of attention deficit hyperactivity disorder.Animal studies could be used to confirm microRNA findings in human patients and to test the effects of targeting specific microRNAs on disease progression and behavior.
文摘Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.
文摘Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.
基金This work was supported by the Sao Paulo Research Foundation(FAPESP)(Grant Numbers 20/11946-6,18/05821-6,17/10201-4,09/08535-5,19/20894-2,and 19/10666-2)the Brazilian National Council for Scientific and Technological Development(CNPq)(Grant Numbers 164937/2020-0,309832/2021-7,308117/2018-2,307718/2018-2,and 409521/2021-3)the Pro-Reitoria de Pesquisa(PROPe)of Sao Paulo State University(UNESP),and the IDOR/Pioneer Science Initiative(www.pioneerscience.org).
文摘Background:Near-infrared spectroscopy(NIRS)technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise.Since this technology has been growing and is now successfully used in laboratory and sports settings,this systematic review aimed to synthesize the evidence and enhance an integrative understanding of bloodflow adjustments and oxygen(O_(2))changes(i.e.,the balance between O_(2) delivery and O_(2) consumption)within the cerebral and muscle systems during exercise.Methods:A systematic review was conducted using PubMed,Embase,Scopus,and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise.This review considered manuscripts written in English and available before February 9,2023.Each step of screening involved evaluation by 2 inde-pendent authors,with disagreements resolved by a third author.The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.Results:Twenty studies were included,of which 80%had good methodological quality,and involved 290 young or middle-aged adults.Different types of exercises were used to assess cerebral and muscle hemodynamic changes,such as cycling(n=11),treadmill(n=1),knee extension(n=5),isometric contraction of biceps brachii(n=3),and duet swim routines(n=1).The cerebral hemodynamics anal-ysis was focused on the frontal cortex(n=20),while in the muscle,the analysis involved vastus lateralis(n=18),gastrocnemius(n=3),biceps brachii(n=5),deltoid(n=1),and intercostal muscle(n=1).Overall,muscle deoxygenation increases during exercise,reaching a plateau in voluntary exhaustion,while in the brain,oxyhemoglobin concentration increases with exercise intensity,reaching a plateau or declining at the exhaustion point.Conclusion:Muscle and cerebral oxygenation respond differently to exercise,with muscle increasing O_(2) utilization and cerebral tissue increasing O_(2) delivery during exercise.However,at the exhaustion point,both muscle and cerebral oxygenation become compromised.This is characterized by a reduction in bloodflow and a decrease in O_(2) extraction in the muscle,while in the brain,oxygenation reaches a plateau or decline,potentially resulting in motor failure during exercise.
基金funding from European Regional Development Fund(project No 13.1.1-LMT-K-718-05-0005)under grant agreement with the Research Council of Lithuania(LMTLT)。
文摘The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.
基金the National Natural Science Foundation of China(No.82172114)the Anhui Provincial Natural Science Foundation for Distinguished Young Scholars(No.2108085J37).
文摘Cryopreservation of red blood cells(RBCs)provides great potential benefits for providing transfusion timely in emergencies.High concentrations of glycerol(20%or 40%)are used for RBC cryopreservation in current clinical practice,which results in cytotoxicity and osmotic injuries that must be carefully controlled.However,existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels,which require relatively large storage space and an extra concentration process before transfusion,making it inconvenient(time-consuming,and also may cause injury and sample lose)for clinical applications.To this end,we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core–shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation.Different from previous studies,we achieve the cryopreservation of human RBCs at high hematocrit(>40%)with high recovery(up to 95%).Additionally,the washed RBCs post-cryopreserved are proved to maintain their morphology,mechanics,and functional properties.This may provide a nontoxic,high-efficiency,and glycerol-free approach for RBC cryopreservation,along with potential clinical transfusion benefits.
基金supported by National Natural Science Foundation of China[grant number U21A20399]Liaoning Revitalization Talents Program[grant number XLYC1802059]+2 种基金the Key R&D Program of Liaoning Province[grant number2019JH2/10300044]the Key Laboratory Program of Liaoning Province[grant number 2018225113]the Key Laboratory Program of Shenyang City[grant number 21-103-0-16]。
文摘Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.
基金The College Students’ Innovative Entrepreneurial Training Plan Program [202110594024]Science and Technology Plan Projects of Liuzhou [2022CAC0299]
文摘Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
文摘Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.
基金Suranaree University of Technology,Thailand Science Research and Innovation(TSRI)National Science,Research,and Innovation Fund(NSRF)(NRIIS Number 179292).
文摘Monitoring blood pressure is a critical aspect of safeguarding an individual’s health,as early detection of abnormal blood pressure levels facilitates timely medical intervention,ultimately leading to a reduction in mortality rates associated with cardiovascular diseases.Consequently,the development of a robust and continuous blood pressure monitoring system holds paramount significance.In the context of this research paper,we introduce an innovative deep learning regression model that harnesses phonocardiogram(PCG)data to achieve precise blood pressure estimation.Our novel approach incorporates a convolutional neural network(CNN)-based regression model,which not only enhances its adaptability to spatial variations but also empowers it to capture intricate patterns within the PCG signals.These advancements contribute significantly to the overall accuracy of blood pressure estimation.To substantiate the effectiveness of our proposed method,we meticulously gathered PCG signal data from 78 volunteers,adhering to the ethical guidelines of Suranaree University of Technology(Human Research Ethics number EC-65-78).Subsequently,we rigorously preprocessed the dataset to ensure its integrity.We further employed a K-fold cross-validation procedure for data division and alignment,combining the resulting datasets with a CNNfor blood pressure estimation.The experimental results are highly promising,yielding aMeanAbsolute Error(MAE)and standard deviation(STD)of approximately 10.69±7.23 mmHg for systolic pressure and 6.89±5.22 mmHg for diastolic pressure.Our study underscores the potential for precise blood pressure estimation,particularly using PCG signals,paving the way for a practical,non-invasive method with broad applicability in the healthcare domain.Early detection of abnormal blood pressure levels can facilitate timely medical interventions,ultimately reducing cardiovascular disease-related mortality rates.
文摘BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.
文摘Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.
基金financially supported by Key Project of State Key R&D Program,China (2022YFF1100200)the Program for Science&Technology Innovation Platform of Hunan Province (2019TP102)+3 种基金Natural Science Foundation of Hunan Province (2021JJ31075,2019JJ50984)Natural Science Foundation of Changsha City (kq2014275)Scientific Innovation Fund for Postgraduates of Central South University of Forestry and Technology (CX20200699,CX202102067)Postgraduate Scientific Research Innovation Project of Hunan Province (CX20201018,CX20210899,CX20220701 and CX20220720)。
文摘Dietary parboiled rice(PR)has a low risk of disease,but little is known about the contribution of PR to the prevention of hyperlipidemia.The potential role and underlying mechanisms of PR in hyperlipidemia were evaluated in this study.Male C57BL/6J mice were fed with a normal diet,high-fat diet(HFD)containing refined rice(HFDRR)or PR(HFDPR).It was found that PR intervention improved lipid accumulation in mice.Transcriptomic data analysis revealed that 27 genes were up-regulated(mostly involved in lipid breakdown)and 86 genes were down-regulated(mostly involved in inflammatory responses)in the HFDPR group compared to the HFDRR group.And 15 differentially expressed genes(DEGs)were validated by quantitative real-time PCR(RT-qPCR),while protein interaction network showed that protein tyrosine phosphatase receptor type C(PTPRC)has a central role.The gut microbiota of mice was also altered after different dietary treatments,with higher ratio of Firmicutes and Bacteroidetes,increased abundances of Ruminococcaceae,Lachnospiraceae,Christensenellaceae,Porphyromonadaceae,Rikenellaceae and Prevotellaceae,and decreased abundances of Lactobacillaceae,Peptostreptococcaceae,Erysipelotrichaceae and Actinobacteria in the HFDRR group.In addition,it was observed that PPAR signaling pathway may act as a bridge between DEGs and differential gut microbiota.These results suggested that PR can prevent hyperlipidemia by modulating liver genes and gut microbiota.
文摘Objective:This study aimed to identify predictive factors for percutaneous nephrolithotomy(PCNL)bleeding risks.With better risk stratification,bleeding in high-risk patient can be anticipated and facilitates early identification.Methods:A prospective observational study of PCNL performed at our institution was done.All adults with radio-opaque renal stones planned for PCNL were included except those with coagulopathy,planned for additional procedures.Factors including gender,co-morbidities,body mass index,stone burden,puncture site,tract dilatation size,operative position,surgeon's seniority,and operative duration were studied using stepwise multivariate regression analysis to identify the predictive factors associated with higher estimated hemoglobin(Hb)deficiency.Results:Overall,4.86%patients(n=7)received packed cells transfusion.The mean estimated Hb deficiency was 1.3(range 0-6.5)g/dL and the median was 1.0 g/dL.Stepwise multivariate regression analysis revealed that absence of hypertension(p=0.024),puncture site(p=0.027),and operative duration(p=0.023)were significantly associated with higher estimated Hb deficiency.However,the effect sizes are rather small with partial eta-squared of 0.037,0.066,and 0.038,respectively.Observed power obtained was 0.621,0.722,and 0.625,respectively.Other factors studied did not correlate with Hb difference.Conclusion:Hypertension,puncture site,and operative duration have significant impact on estimated Hb deficiency during PCNL.However,the effect size is rather small despite adequate study power obtained.Nonetheless,operative position(supine or prone),puncture number,or tract dilatation size did not correlate with Hb difference.The mainstay of reducing bleeding in PCNL is still meticulous operative technique.Our study findings also suggest that PCNL can be safely done by urology trainees under supervision in suitably selected patient,without increasing risk of bleeding.