Objectives: To determine the level of adversity quotient and its associations with rumination, optimism, and authoritative parenting style in junior high school students. Adversity quotient is the adaptation ability t...Objectives: To determine the level of adversity quotient and its associations with rumination, optimism, and authoritative parenting style in junior high school students. Adversity quotient is the adaptation ability to overcome problems and obstacles with a positive attitude. Early adolescence, as a critical stage of life, needs to cultivate adversity quotient. However, adversity quotient and its influencing factors in adolescents have not been fully understood. Methods: A total of 129 students from 3 junior high schools (grade 7-9) in Chon Buri province, Thailand, were randomly recruited to participate in this correlational research study. They completed 5 questionnaires including the demographic form, adversity quotient assessment, authoritative parenting style, optimism, and rumination. Descriptive statistics and Pearson’s correlation coefficient were used for data analysis. Results: Adversity quotient was at a moderate level with a mean of 138.78 (standard deviation [SD] = 21.25). Adversity quotient was significantly, positively correlated with authoritative parenting at the highest level (r = 0.60), followed by optimism at a moderate level (r = 0.38), and rumination at a low level (r = 0.25, P < 0.01). Conclusions: All parties responsible for early adolescents’ development should enhance the adversity quotient to a higher level through campaigns promoting authoritative parenting and optimism. An unexpected positive correlation between adversity quotient and rumination warrants cautious interpretation and more studies.展开更多
BACKGROUND Depression is a common mental disorder among adolescents,characterized by a high rate of suicide and self-harm,which not only is devastating to families but also has a negative impact on society.Psychologic...BACKGROUND Depression is a common mental disorder among adolescents,characterized by a high rate of suicide and self-harm,which not only is devastating to families but also has a negative impact on society.Psychological factors such as impulsive personality,perceived chronic social adversity(PCSA),and sense of security are closely associated with suicide risk in adolescents with depression.Few studies have been conducted on the relationship between these factors.AIM To explore the impact of impulsive personality on suicide risk in adolescents with depression and the chain mediating effect between PCSA and sense of security.METHODS This study is a retrospective study.A total of 200 adolescents with depression who visited the Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from January 2021 to December 2023 comprised the study cohort.The PCSA scale,Security Questionnaire,Barratt Impulsiveness Scale,and Beck Scale for Suicide Ideation were used to evaluate depression.RESULTS Suicide risk was positively correlated with impulsive personality and PCSA(P<0.05),whereas sense of security was negatively correlated with suicide risk,impulsive personality,and PCSA(P<0.05).The total indirect effect of PCSA and sense of security on impulsive personality and suicide risk was 35.43%,with the mediating effect of PCSA and sense of security contributing 16.53%and 15.75%,respectively.PCSA and sense of security exhibited a chain mediating effect between impulsive personality and suicide risk,accounting for 3.15%.CONCLUSION The suicide risk of adolescents with depression is significantly associated with impulsive personality,PCSA,and sense of security.Impulsive personality affects the suicide risk of adolescents with depression both directly and indirectly,with the latter occurring via PCSA and sense of security.展开更多
The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with dif...The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome？ DNA methylation is an enzymatically- catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.展开更多
In the laboratory,environmental enrichment（EE）is used as a protocol to understand the functional,behavioral and molecular mechanisms that underlie neural plasticity（van Praag et al.,2000;Sale et al.,2014）.In addit...In the laboratory,environmental enrichment（EE）is used as a protocol to understand the functional,behavioral and molecular mechanisms that underlie neural plasticity（van Praag et al.,2000;Sale et al.,2014）.In addition,it is utilized to provide supplementary resources to animals in order to maintain their well-being and to preserve the scientific validity of the study at hand（see http：//www.nap.edu/catalog/12910/guide-for-thecare-and-use-of-laboratory-animals-eighth）.展开更多
Socially disadvantaged individuals with HIV experience unacceptably high rates of AIDS and death. The authors developed an adversity index to quantify the impact of demographic and psychosocial factors on HIV care. Th...Socially disadvantaged individuals with HIV experience unacceptably high rates of AIDS and death. The authors developed an adversity index to quantify the impact of demographic and psychosocial factors on HIV care. This retrospective cohort study included 431 participants with HIV on combined antiretroviral therapy between 2000 and 2005. Poor outcome was defined as progression to AIDS, death, virologic failure, or CD4 < 200 cells/μl at six months. The index utilized eight demographic and psychosocial variables independently associated with poor outcome. Exposure to higher numbers of variables in the adversity index significantly increased the rates of poor outcome from 14% (exposure to no variables) to 100% (exposure to seven variables). The odds of poor outcome decreased but remained significant after adjusting for adherence-defining variables, indicating a possible mediating effect of poor adherence. Durably effective therapeutic strategies must include addressing adverse demographic and psychosocial factors affecting people living with HIV.展开更多
Chinese companies join the fight against COVID-19 throughout Africa At a Chinese electricity project deep inside Uganda,Muzinga Hamis and his colleagues put up numerous signs reminding staff and villagers to wear mask...Chinese companies join the fight against COVID-19 throughout Africa At a Chinese electricity project deep inside Uganda,Muzinga Hamis and his colleagues put up numerous signs reminding staff and villagers to wear masks,practice social distancing and check their body daily.展开更多
IS there an audience for a Mauritanian director promoting a movie about Mall in China？ It depends on the director and the film French speakers, film students and film lovers packed the China Film Archive auditorium t...IS there an audience for a Mauritanian director promoting a movie about Mall in China？ It depends on the director and the film French speakers, film students and film lovers packed the China Film Archive auditorium to watch Abderrahmane Sissako＇s famous film Timbuktu with the director himself.展开更多
ObjectiveTo present an approach to phenotyping ACEs and explore the association between ACEs and adolescent health risky behaviors based on the social context of China.Methods Totally,5,726 adolescents aged 12-18 year...ObjectiveTo present an approach to phenotyping ACEs and explore the association between ACEs and adolescent health risky behaviors based on the social context of China.Methods Totally,5,726 adolescents aged 12-18 years were investigated about their ACEs in the family,peer,school,and personal domains and the occurrence of six types of risky health behaviors(i.e.,smoking,drinking,sexual intercourse,self-harm,and suicidal ideation and attempts).Latent class analysis(LCA)was used to explore the ACE patterns.Results Six latent classes of ACEs were identified,including low adversity,school adversity,school adversity and peer victimization,peer victimization,maltreatment and peer victimization,and high adversity,and associated with risky health behaviors in adolescents.Being physically punished by a teacher,experiencing sexual abuse,and experiencing family trauma most strongly differentiated from the six AcE classes and were correlated with an increased risk for risky adolescent health behaviors.ConclusionThis study supports a positive association between ACEs and risky adolescent health behaviors.Peer victimization,school adversity and associated contexts need to be considered in future ACEstudies.展开更多
Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious a...Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that env...Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases.Early life adversity(ELA)has a profound impact on brain function and health later in life.In rodent models,exposure to ELA results in specific cognitive deficits and aggravated AD pathology.Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA.In this review,we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD.These discoveries suggest that ELA,especially at early postnatal stages,increases susceptibility to cognitive impairment and AD later in life.In terms of mechanisms,ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis,altered gut microbiome,persistent inflammation,oligodendrocyte dysfunction,hypomyelination,and aberrant adult hippocampal neurogenesis.Crosstalks among these events may synergistically contribute to cognitive impairment later in life.Additionally,we discuss several interventions that may alleviate adverse consequences of ELA.Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.展开更多
BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion...BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion(TCI)can provide safe sedation but may require higher dosages of propofol.On the contrary,etomidate offers hemodynamic stability.AIM To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy.METHODS A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups:P,0.1EP,and 0.15EP.Patients in the P group received propofol TCI only,with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL.Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection,respectively,followed by propofol TCI.RESULTS Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups(P group:78 mmHg,0.1EP group:82 mmHg,0.15EP group:88 mmHg;P<0.05).Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups(P group:260.6 mg,0.1EP group:228.1 mg,0.15EP group:201.2 mg;P<0.05).The induction time was longer in the P group than in the other groups(P group:1.9±0.7 minutes,0.1EP group:1.2±0.4 minutes,0.15EP group:1.1±0.3 minutes;P<0.01).The recovery time was shorter in the 0.15EP group than in the other groups(P group:4.8±2.1 minutes,0.1EP group:4.5±1.6 minutes,0.15EP group:3.9±1.4 minutes;P<0.01).The incidence of hypotension(P group:36.4%,0.1EP group:29.1%,0.15EP group:11.8%;P<0.01)and injection pain was lower in the 0.15EP group than in the other groups(P<0.05).Furthermore,the incidence of respiratory depression was lower in the 0.15EP group than in the P group(P<0.05).Additionally,the satisfaction of the patient,endoscopist,and anesthesiologist was higher in the 0.15EP group than in the other groups(P<0.05).CONCLUSION Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption,which is followed by fewer cardiovascular adverse events and respiratory depression,along with higher patient,endoscopist,and anesthesiologist satisfaction.展开更多
BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery ...BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term survival.Accurate preoperative identification of high-risk patients is critical for improving outcomes.AIM To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.METHODS This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February 2024.Patients were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of SAEs.RESULTS SAEs occurred in 10.2%of patients in train set and 13.6%in the validation set.Patients with SAE had significantly higher complication rate and a longer hospital stay after surgery.The key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin levels.The stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation set.CONCLUSION The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.展开更多
BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardi...BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardiac monitoring.CASE SUMMARY Two patients with non-small cell lung cancer developed SSS after 15 months and 5 months of anlotinib treatment,respectively,presenting with syncope and palpit-ations.Electrocardiogram confirmed SSS,and different treatment approaches were taken for each patient.One patient received a dual-chamber permanent pacemaker,while the other discontinued the medication and experienced symptom resolution.CONCLUSION Anlotinib can induce SSS,suggesting that cardiac monitoring is crucial during anlotinib treatment.Individualized management strategies are necessary for affected individuals.展开更多
Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serio...Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.展开更多
BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to...BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.展开更多
BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events...BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.展开更多
Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for me...Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for medication-induced urticaria through comprehensive analysis of the FDA Adverse Event Reporting System(FAERS)database.Methods:We employed reporting odds ratios(ROR)to evaluate drug-urticaria associations using FAERS data spanning from Q12004 to Q32024.Analytical approaches included univariate screening,LASSO regression,and multivariate logistic regression to identify potential risk factors.Multiple comparison adjustments were implemented using the Bonferroni method.Results:The study identified 1807 pharmaceutical agents potentially associated with urticaria development.Univariate analysis categorized these agents into several therapeutic classes:antimicrobials(19/85),biologics(16/85),analgesics(8/85),dermatologicals(3/85),anti-rheumatic agents(4/85),hormonal preparations(3/85),antihypertensives(2/85),neuropsychiatric medications(2/85),uric acid-lowering drugs(2/85),multiple sclerosis therapies(2/85),and miscellaneous agents(17/85).Multivariate analysis identified three significant risk determinants:middle-aged individuals(36-53 years),female gender,and exposure to any of 82 specific medications.Conclusion:These evidence-based findings provide valuable insights for early clinical recognition of drug-induced urticaria and establish a foundation for subsequent mechanistic investigations into medication-related hypersensitivity reactions.展开更多
Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment ...Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.展开更多
Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.Ho...Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.展开更多
基金supported by the Faculty of Nursing Burapha University(No.19/2561).
文摘Objectives: To determine the level of adversity quotient and its associations with rumination, optimism, and authoritative parenting style in junior high school students. Adversity quotient is the adaptation ability to overcome problems and obstacles with a positive attitude. Early adolescence, as a critical stage of life, needs to cultivate adversity quotient. However, adversity quotient and its influencing factors in adolescents have not been fully understood. Methods: A total of 129 students from 3 junior high schools (grade 7-9) in Chon Buri province, Thailand, were randomly recruited to participate in this correlational research study. They completed 5 questionnaires including the demographic form, adversity quotient assessment, authoritative parenting style, optimism, and rumination. Descriptive statistics and Pearson’s correlation coefficient were used for data analysis. Results: Adversity quotient was at a moderate level with a mean of 138.78 (standard deviation [SD] = 21.25). Adversity quotient was significantly, positively correlated with authoritative parenting at the highest level (r = 0.60), followed by optimism at a moderate level (r = 0.38), and rumination at a low level (r = 0.25, P < 0.01). Conclusions: All parties responsible for early adolescents’ development should enhance the adversity quotient to a higher level through campaigns promoting authoritative parenting and optimism. An unexpected positive correlation between adversity quotient and rumination warrants cautious interpretation and more studies.
文摘BACKGROUND Depression is a common mental disorder among adolescents,characterized by a high rate of suicide and self-harm,which not only is devastating to families but also has a negative impact on society.Psychological factors such as impulsive personality,perceived chronic social adversity(PCSA),and sense of security are closely associated with suicide risk in adolescents with depression.Few studies have been conducted on the relationship between these factors.AIM To explore the impact of impulsive personality on suicide risk in adolescents with depression and the chain mediating effect between PCSA and sense of security.METHODS This study is a retrospective study.A total of 200 adolescents with depression who visited the Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from January 2021 to December 2023 comprised the study cohort.The PCSA scale,Security Questionnaire,Barratt Impulsiveness Scale,and Beck Scale for Suicide Ideation were used to evaluate depression.RESULTS Suicide risk was positively correlated with impulsive personality and PCSA(P<0.05),whereas sense of security was negatively correlated with suicide risk,impulsive personality,and PCSA(P<0.05).The total indirect effect of PCSA and sense of security on impulsive personality and suicide risk was 35.43%,with the mediating effect of PCSA and sense of security contributing 16.53%and 15.75%,respectively.PCSA and sense of security exhibited a chain mediating effect between impulsive personality and suicide risk,accounting for 3.15%.CONCLUSION The suicide risk of adolescents with depression is significantly associated with impulsive personality,PCSA,and sense of security.Impulsive personality affects the suicide risk of adolescents with depression both directly and indirectly,with the latter occurring via PCSA and sense of security.
基金supported by a grant from the Canadian Institute of Health Research to M.S. M.Ssupported by the Sackler program in epigenetics and psychobiology at McGill University,Canada
文摘The impact of early physical and social environments on life-long phenotypes is well known. Moreover, we have documented evidence for gene-environment interactions where identical gene variants are associated with different phenotypes that are dependent on early life adversity. What are the mechanisms that embed these early life experiences in the genome？ DNA methylation is an enzymatically- catalyzed modification of DNA that serves as a mechanism by which similar sequences acquire cell type identity during cellular differentiation and embryogenesis in the same individual. The hypothesis that will be discussed here proposes that the same mechanism confers environmental-exposure specific identity upon DNA providing a mechanism for embedding environmental experiences in the genome, thus affecting long-term phenotypes. Particularly important is the environment early in life including both the prenatal and postnatal social environments.
文摘In the laboratory,environmental enrichment（EE）is used as a protocol to understand the functional,behavioral and molecular mechanisms that underlie neural plasticity（van Praag et al.,2000;Sale et al.,2014）.In addition,it is utilized to provide supplementary resources to animals in order to maintain their well-being and to preserve the scientific validity of the study at hand（see http：//www.nap.edu/catalog/12910/guide-for-thecare-and-use-of-laboratory-animals-eighth）.
文摘Socially disadvantaged individuals with HIV experience unacceptably high rates of AIDS and death. The authors developed an adversity index to quantify the impact of demographic and psychosocial factors on HIV care. This retrospective cohort study included 431 participants with HIV on combined antiretroviral therapy between 2000 and 2005. Poor outcome was defined as progression to AIDS, death, virologic failure, or CD4 < 200 cells/μl at six months. The index utilized eight demographic and psychosocial variables independently associated with poor outcome. Exposure to higher numbers of variables in the adversity index significantly increased the rates of poor outcome from 14% (exposure to no variables) to 100% (exposure to seven variables). The odds of poor outcome decreased but remained significant after adjusting for adherence-defining variables, indicating a possible mediating effect of poor adherence. Durably effective therapeutic strategies must include addressing adverse demographic and psychosocial factors affecting people living with HIV.
文摘Chinese companies join the fight against COVID-19 throughout Africa At a Chinese electricity project deep inside Uganda,Muzinga Hamis and his colleagues put up numerous signs reminding staff and villagers to wear masks,practice social distancing and check their body daily.
文摘IS there an audience for a Mauritanian director promoting a movie about Mall in China？ It depends on the director and the film French speakers, film students and film lovers packed the China Film Archive auditorium to watch Abderrahmane Sissako＇s famous film Timbuktu with the director himself.
基金This study has been supported by grants from the National Natural Science Foundation of China[Grant number 81874268].
文摘ObjectiveTo present an approach to phenotyping ACEs and explore the association between ACEs and adolescent health risky behaviors based on the social context of China.Methods Totally,5,726 adolescents aged 12-18 years were investigated about their ACEs in the family,peer,school,and personal domains and the occurrence of six types of risky health behaviors(i.e.,smoking,drinking,sexual intercourse,self-harm,and suicidal ideation and attempts).Latent class analysis(LCA)was used to explore the ACE patterns.Results Six latent classes of ACEs were identified,including low adversity,school adversity,school adversity and peer victimization,peer victimization,maltreatment and peer victimization,and high adversity,and associated with risky health behaviors in adolescents.Being physically punished by a teacher,experiencing sexual abuse,and experiencing family trauma most strongly differentiated from the six AcE classes and were correlated with an increased risk for risky adolescent health behaviors.ConclusionThis study supports a positive association between ACEs and risky adolescent health behaviors.Peer victimization,school adversity and associated contexts need to be considered in future ACEstudies.
基金Supported by CONAHCYT Project,No.CF-2023-I-2663Instituto Nacional de Psiquiatría Project,No.NC24208.0(to Pérez-Sánchez G,Pavón L,Sánchez-Huerta K,Maldonado-García JL,Chin-Chan JM,Ponce-Regalado MD,Arreola R,Contis-Montes de Oca A,and Moreno-Lafont MC).
文摘Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
基金supported by the National Institute on Aging of the National Institutes of Health under Award Number RF1AG058603.
文摘Neurological conditions,including cognitive impairment and Alzheimer’s disease(AD),impose a huge burden on society,affecting millions of people globally.In addition to genetic factors,recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases.Early life adversity(ELA)has a profound impact on brain function and health later in life.In rodent models,exposure to ELA results in specific cognitive deficits and aggravated AD pathology.Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA.In this review,we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD.These discoveries suggest that ELA,especially at early postnatal stages,increases susceptibility to cognitive impairment and AD later in life.In terms of mechanisms,ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis,altered gut microbiome,persistent inflammation,oligodendrocyte dysfunction,hypomyelination,and aberrant adult hippocampal neurogenesis.Crosstalks among these events may synergistically contribute to cognitive impairment later in life.Additionally,we discuss several interventions that may alleviate adverse consequences of ELA.Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.
文摘BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion(TCI)can provide safe sedation but may require higher dosages of propofol.On the contrary,etomidate offers hemodynamic stability.AIM To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy.METHODS A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups:P,0.1EP,and 0.15EP.Patients in the P group received propofol TCI only,with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL.Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection,respectively,followed by propofol TCI.RESULTS Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups(P group:78 mmHg,0.1EP group:82 mmHg,0.15EP group:88 mmHg;P<0.05).Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups(P group:260.6 mg,0.1EP group:228.1 mg,0.15EP group:201.2 mg;P<0.05).The induction time was longer in the P group than in the other groups(P group:1.9±0.7 minutes,0.1EP group:1.2±0.4 minutes,0.15EP group:1.1±0.3 minutes;P<0.01).The recovery time was shorter in the 0.15EP group than in the other groups(P group:4.8±2.1 minutes,0.1EP group:4.5±1.6 minutes,0.15EP group:3.9±1.4 minutes;P<0.01).The incidence of hypotension(P group:36.4%,0.1EP group:29.1%,0.15EP group:11.8%;P<0.01)and injection pain was lower in the 0.15EP group than in the other groups(P<0.05).Furthermore,the incidence of respiratory depression was lower in the 0.15EP group than in the P group(P<0.05).Additionally,the satisfaction of the patient,endoscopist,and anesthesiologist was higher in the 0.15EP group than in the other groups(P<0.05).CONCLUSION Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption,which is followed by fewer cardiovascular adverse events and respiratory depression,along with higher patient,endoscopist,and anesthesiologist satisfaction.
基金Supported by Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9187 and No.2021Y9057.
文摘BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term survival.Accurate preoperative identification of high-risk patients is critical for improving outcomes.AIM To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.METHODS This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February 2024.Patients were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of SAEs.RESULTS SAEs occurred in 10.2%of patients in train set and 13.6%in the validation set.Patients with SAE had significantly higher complication rate and a longer hospital stay after surgery.The key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin levels.The stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation set.CONCLUSION The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.
文摘BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardiac monitoring.CASE SUMMARY Two patients with non-small cell lung cancer developed SSS after 15 months and 5 months of anlotinib treatment,respectively,presenting with syncope and palpit-ations.Electrocardiogram confirmed SSS,and different treatment approaches were taken for each patient.One patient received a dual-chamber permanent pacemaker,while the other discontinued the medication and experienced symptom resolution.CONCLUSION Anlotinib can induce SSS,suggesting that cardiac monitoring is crucial during anlotinib treatment.Individualized management strategies are necessary for affected individuals.
文摘Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.
文摘BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.
文摘BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.
文摘Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for medication-induced urticaria through comprehensive analysis of the FDA Adverse Event Reporting System(FAERS)database.Methods:We employed reporting odds ratios(ROR)to evaluate drug-urticaria associations using FAERS data spanning from Q12004 to Q32024.Analytical approaches included univariate screening,LASSO regression,and multivariate logistic regression to identify potential risk factors.Multiple comparison adjustments were implemented using the Bonferroni method.Results:The study identified 1807 pharmaceutical agents potentially associated with urticaria development.Univariate analysis categorized these agents into several therapeutic classes:antimicrobials(19/85),biologics(16/85),analgesics(8/85),dermatologicals(3/85),anti-rheumatic agents(4/85),hormonal preparations(3/85),antihypertensives(2/85),neuropsychiatric medications(2/85),uric acid-lowering drugs(2/85),multiple sclerosis therapies(2/85),and miscellaneous agents(17/85).Multivariate analysis identified three significant risk determinants:middle-aged individuals(36-53 years),female gender,and exposure to any of 82 specific medications.Conclusion:These evidence-based findings provide valuable insights for early clinical recognition of drug-induced urticaria and establish a foundation for subsequent mechanistic investigations into medication-related hypersensitivity reactions.
基金supported by #NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-(DN.155311.10.2022)supported by Sapienza Grant 2021(RM12117A60BDF685).
文摘Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.
基金the Canadian Institutes of Health Research(CIHR),Grant/Award Number:PJT-175016the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641+2 种基金the Quebec Cell,Tissue and Gene Therapy Network—ThéCellthe FRQS,the Fondation du CHU de Québec-UniversitéLavalNeuro Québec。
文摘Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
