Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a histo...Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.展开更多
BACKGROUND:The nonspecifi c clinical presentation of adrenal insuffi ciency(AI)frequently leads to misdiagnosis,often as psychiatric or gastrointestinal disorders.AI is classifi ed anatomically as primary AI(PAI),seco...BACKGROUND:The nonspecifi c clinical presentation of adrenal insuffi ciency(AI)frequently leads to misdiagnosis,often as psychiatric or gastrointestinal disorders.AI is classifi ed anatomically as primary AI(PAI),secondary AI(SAI),or tertiary AI(TAI).Without timely recognition,progression to adrenal crisis(AC)can result in life-threatening outcomes.This study aimed to systematically analyze the clinical features,etiologies,and outcomes of AI in Lhasa’s emergency population to improve diagnostic accuracy and optimize clinical management.METHODS:A retrospective analysis of emergency department admissions from January 2020 to August 2024 at People’s Hospital of Xizang Autonomous Region was conducted.AI diagnoses were identifi ed via International Classifi cation of Diseases,Tenth Revision,Clinical Modifi cation(ICD-10-CM)codes from electronic health records(EHR).Patients were grouped into incipient AC(IAC)or AC cohorts based on hemodynamic status.Demographic profi les,etiologies,clinical presentations,and laboratory results were analyzed.RESULTS:Forty-three AI patients were identifi ed.The population-standardized admission rate for AI increased from 9 to 16 per million person-years,with PAI cases doubling during this period.Adrenal tuberculosis(58.1%)and adrenal hematoma(18.6%)were the leading etiologies.Compared to the IAC group,the AC group demonstrated lower systolic blood pressure(SBP)(P=0.001)and diastolic blood pressure(DBP)(P<0.001);higher neutrophil count(P=0.048),eosinophil count(P=0.044),CRP(P=0.004),blood urea nitrogen(BUN)(P=0.007);lower sodium(P<0.001)and glucose levels(P=0.001).The hospital stay was longer in the AC group(20 d vs.14 d;P<0.001).CONCLUSION:AI incidence is rising in high-altitude regions,with adrenal tuberculosis remaining the most common cause.AC is associated with increased inflammatory responses,hemodynamic instability,and metabolic disturbances.Targeted interventions are required to improve outcomes.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about ...BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.展开更多
BACKGROUND Liver injury manifesting as hepatic enzyme abnormalities,has been occasionally identified to be a feature of primary or secondary Addison's disease,an uncommon endocrine disease characterized by adrenal...BACKGROUND Liver injury manifesting as hepatic enzyme abnormalities,has been occasionally identified to be a feature of primary or secondary Addison's disease,an uncommon endocrine disease characterized by adrenal insufficiency.There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease.Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer.CASE SUMMARY A 42-year-old man presented with fatigue and mildly elevated transaminases.Laboratory investigations and imaging studies excluded common etiologies of liver injury.Based on the fact that the patient discontinued long-term therapy with prednisone approximately 2 weeks before he was found to have elevated transaminase levels and the observation that his cortisol was lower than the normal value,he was diagnosed as having hypertransaminasemia secondary to adrenal insufficiency caused by glucocorticoid withdrawal.The patient was infused intravenously with compound diisopropylamine dichloroacctate and compound glycyrrhizin,and his transaminase levels returned to normal after 1 week.Approximately 2 years later,the patient received hydroprednisone treatment for 2 days in an endoscopic sinus surgery.Eight days after he discontinued the hydroprednisone treatment,he developed symptoms reminiscent of glucocorticoid withdrawal syndrome.These symptoms resolved spontaneously after 1 week.Intriguingly,the patient did not develop hepatic dysfunction this time.CONCLUSION The present case,showing some unusual clinical features,highlights the importance of education of clinicians and patients to avoid improper discontinuation of glucocorticoid therapy and complete history taking for prompt recognition.展开更多
BACKGROUND Adrenal ectopia is a rare condition in which adrenal tissue is found in an abn-ormal location,often posing diagnostic challenges.Although generally considered benign,it can present as hepatic or other organ...BACKGROUND Adrenal ectopia is a rare condition in which adrenal tissue is found in an abn-ormal location,often posing diagnostic challenges.Although generally considered benign,it can present as hepatic or other organ lesions,mimicking malignant tumors.In the liver,ectopic adrenal tissue can closely resemble hepatocellular carcinoma or metastatic disease,potentially leading to unnecessary aggressive treatments such as surgery or chemotherapy.Consequently,a high index of sus-picion is essential to avoid misdiagnosis and ensure appropriate management.CASE SUMMARY In this case report,we present a 53-year-old male with ectopic adrenal tissue in the liver,mimicking a potential hepatic malignancy.Based on computed tomo-graphy and magnetic resonance imaging findings,which suggested a malignant liver lesion and a left adrenal adenoma,the patient underwent laparoscopic partial hepatectomy under general anesthesia.Intraoperatively,no signs of liver cirrhosis were observed.An intraoperative ultrasound identified a 1.2 cm hypo-echoic nodule in segment 7 of the liver.Dissection of the right adrenal gland revealed that the nodule had infiltrated the hepatic parenchyma,confirming the presence of ectopic adrenal tissue.Frozen section pathology revealed proliferating adrenal tissue.The patient recovered smoothly and was discharged 10 days post-operatively.CONCLUSION This case report underscores the importance of considering adrenal ectopia in the differential diagnosis of liver lesions,especially when imaging findings suggest malignancy.展开更多
We present the diagnostic performance of[18F]Fluorodeoxyglucose positron emission tomography(FDG PET)for adrenal incidentalomas based on lesion size and unenhanced computed tomography(CT)density in Hounsfield units(HU...We present the diagnostic performance of[18F]Fluorodeoxyglucose positron emission tomography(FDG PET)for adrenal incidentalomas based on lesion size and unenhanced computed tomography(CT)density in Hounsfield units(HU),following current literature and guidelines.A 20 HU cutoff can be applied to differentiate potentially benign from malignant lesions,particularly in ruling in or out adrenocortical carcinoma.While FDG PET provides valuable metabolic information,its likelihood ratios for a positive(LR+)or negative(LR-)result do not exceed the robust diagnostic thresholds of>10.0 or<0.1,respectively.This suggests that positron emission tomography alone is insufficient for definitive characterization and should be integrated with CT or magnetic resonance imaging to leverage their complementary anatomical and functional imaging strengths for optimal diagnostic accuracy.展开更多
The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additio...The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.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
Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis...Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis,leading to secondary adrenal insufficiency(AI).This condition occurs when the adrenal glands fail to produce adequate cortisol,which is essential for regulating metabolism,immune response,and stress adaptation.Corticotropin-releasing hormone(CRH)from the hypothalamus stimulates the pituitary to release adrenocorticotropic hormone(ACTH),which then triggers cortisol production in the adrenal glands.Prolonged GC use disrupts this system by inhibiting CRH and ACTH secretion,leading to adrenal atrophy and reduced cortisol production.HPA axis suppression is primarily diagnosed through dynamic tests.Early morning cortisol levels above>18 ng/mL typically indicate normal function,while levels<3 ng/mL suggest AI.Intermediate values require additional testing,such as the insulin tolerance test,ACTH stimulation test,and metyrapone test.Prednisolone in nephrotic syndrome suppresses the HPA axis,heightening AI risk,influenced by dose,duration,and timing of administration.Careful GC management is essential to balance disease control with risks of HPA axis suppression.Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients.展开更多
Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance...Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.展开更多
Effects of Mingzhu Oral Liquid on the Hypothalamic-Pituitary-Adrenal Axis in Rats with Liver-Kidney Yin Deficiency WANG Yi-ting1,ZHAO Yang1,ZHU Fei-ya1,WANG Si-qiong1,ZHU Ling-lei1,LI Tao2,TANG Min-ke1,1.Beijing Unive...Effects of Mingzhu Oral Liquid on the Hypothalamic-Pituitary-Adrenal Axis in Rats with Liver-Kidney Yin Deficiency WANG Yi-ting1,ZHAO Yang1,ZHU Fei-ya1,WANG Si-qiong1,ZHU Ling-lei1,LI Tao2,TANG Min-ke1,1.Beijing University of Chinese Medicine,Beijing,100029,China 2.Guangzhou Yitong Technology Co.,Ltd.,Guangzhou,510653,China【ABSTRACT】Objective:This study aimed to observe the effects of Mingzhu Oral Liquid on the hypothalamic-pituitary-adrenal(HPA)axis in rats with“liver-kidney yin deficiency”,in order to provide scientific research support for its clinical application in treating related disorders.Methods:A“liver-kidney yin deficiency”model was established in male Sprague-Dawley(SD)rats using a combination of chronic restraint stress and a single lipopolysaccharide(LPS)challenge.The rats were randomly divided into four groups:a blank control group,a model group,a low-dose Mingzhu Oral Liquid group,and a high-dose Mingzhu Oral Liquid group.The blank control group and model group were given normal saline by gavage,while the treatment groups received respective doses of Mingzhu Oral Liquid.Gavage administration was performed once daily for 30 consecutive days.During this period,all groups except the blank control group were subjected to restraint stress.Following the final gavage,all groups except the blank control received an intraperitoneal injection of LPS.Samples were collected 24 h post-injection.Serum levels of cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP)were measured by enzyme-linked immunosorbent assay(ELISA)to evaluate the model state.The serum concentrations of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),and glucocorticoid(GC)were determined to assess HPA axis activity.Changes in proinflammatory factors[tumor necrosis factor-alpha(TNF-α),interleukin-1 beta(IL-1β)]and the anti-inflammatory factor interleukin-10(IL-10)were also measured.Results:One week into the experiment,the weight gain rate slowed in all stress groups.By the end of the experiment,the body weight of these groups was significantly lower than that of the blank control group.Biochemical and hematological analyses revealed that the model group exhibited a significant decrease in lymphocyte count,an increased cAMP/cGMP ratio,reduced activities of glutathione S-transferase(GST)and glutathione transferase(GLT),elevated levels of blood urea nitrogen(BUN)and serum creatinine(Scr),increased serum contents of TNF-αand IL-1β,and a decreased content of IL-10.These findings confirmed the successful establishment of the rat model.Although the body weight of animals treated with Mingzhu Oral Liquid remained lower than that of the normal group,the treatment improved weight gain compared to the model group.Furthermore,Mingzhu Oral Liquid administration increased lymphocyte count,decreased the cAMP/cGMP ratio,restored GST and GLT activities,reduced BUN and Scr levels,lowered serum TNF-αand IL-1βcontents,and increased IL-10 levels,indicating a significant ameliorative effect on the deficiency symptoms.Additionally,serum levels of CRH,ACTH,and GC were elevated in the model rats,suggesting HPA axis hyperactivity.Treatment with Mingzhu Oral Liquid reduced the serum concentrations of these hormones,significantly alleviating the excited state of the HPA axis in stressed rats.Conclusion:Mingzhu Oral Liquid significantly improves the abnormal overall physical signs,blood biochemical parameters,and systemic inflammation in rats with“liver-kidney yin deficiency.”These therapeutic effects may be associated with the corrective action of Mingzhu Oral Liquid on the dysfunctional HPA axis in this model.展开更多
Objective: To inquire into diagnosis, and treatment of virilizing andfeminizing a-drenal syndrome, differential diagnosis between benign and malignant sex hormoneproducing adrenal neo-plasma and, treatment principles ...Objective: To inquire into diagnosis, and treatment of virilizing andfeminizing a-drenal syndrome, differential diagnosis between benign and malignant sex hormoneproducing adrenal neo-plasma and, treatment principles of congenital adrenal hyperplasia (CAH).Methods: Eight cases of CAH and 5 cases of sex hormone producing adrenal neoplasma were admitted tohospital during 1986-1996. The former included 3 rare cases of 17 a hydroxylase deficiency. Thelatter included 3 cases of feminizing adrenal tumor and 2 cases of virilizing adrenal tumor.Results: Weight, size and CT of the tumor, DHEA, 17 -ks, sex hormone levels, infiltration, andmetastasis were closely related to the degree of differentiation of the tumors. Conclusion:Virilizing and feminizing adrenal neoplasm were removed surgically by different incisions. Modifiedsubcostal incision was recommended as the best choice for huge adrenal mass. Corticoadrenal hormonetreatment fa CAH should be individualized according to the different types of the disease. Sexhormones were not suitable for children suffering from 17 hydroxylase deficiency before puberty.展开更多
1病例简介肾上腺黑色腺瘤(adrenal black adenoma)又称色素性肾上腺皮质腺瘤(pigmented adrenocortical adenoma),属于一种罕见的肾上腺良性肿瘤[1]。因其细胞内含大量脂褐素或黑色素颗粒,肉眼多呈黑色或褐色,临床上常称其为黑色腺瘤。...1病例简介肾上腺黑色腺瘤(adrenal black adenoma)又称色素性肾上腺皮质腺瘤(pigmented adrenocortical adenoma),属于一种罕见的肾上腺良性肿瘤[1]。因其细胞内含大量脂褐素或黑色素颗粒,肉眼多呈黑色或褐色,临床上常称其为黑色腺瘤。国内外文献报道的仅10余例。我科近期收治表现为库欣综合征的肾上腺黑色腺瘤患者1例,并行腹腔镜肾上腺切除术,手术效果良好。现分析其临床资料报告如下。1病例简介患者,女,60岁,因"发现高血压10年余,查体发现左侧肾上腺腺瘤2天"入院。平素血压最高可至160/100mmHg,不伴夜尿增多。展开更多
In order to explore the molecular mechanisms of children adrenal neuroblastoma,and screen biomarkers for early diagnosis of this disease,the comparative proteomics were done in this report.The total proteins in childr...In order to explore the molecular mechanisms of children adrenal neuroblastoma,and screen biomarkers for early diagnosis of this disease,the comparative proteomics were done in this report.The total proteins in children adrenal neuroblastoma and adrenal control tissues were extracted separately and then separated by 2-DE individually.The protein spots were identified eventually by UPLC-HD-MS.In this research,18 difference proteins including stathmin 1 were found.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
文摘Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.
基金supported by grants from the National Natural Science Foundation of China(82241052)Natural Science Foundation of Xizang Autonomous Region(XZZR202402133[W])Peking University People’s Hospital Scientifi c Research Development Funds(RDJP2023-29).
文摘BACKGROUND:The nonspecifi c clinical presentation of adrenal insuffi ciency(AI)frequently leads to misdiagnosis,often as psychiatric or gastrointestinal disorders.AI is classifi ed anatomically as primary AI(PAI),secondary AI(SAI),or tertiary AI(TAI).Without timely recognition,progression to adrenal crisis(AC)can result in life-threatening outcomes.This study aimed to systematically analyze the clinical features,etiologies,and outcomes of AI in Lhasa’s emergency population to improve diagnostic accuracy and optimize clinical management.METHODS:A retrospective analysis of emergency department admissions from January 2020 to August 2024 at People’s Hospital of Xizang Autonomous Region was conducted.AI diagnoses were identifi ed via International Classifi cation of Diseases,Tenth Revision,Clinical Modifi cation(ICD-10-CM)codes from electronic health records(EHR).Patients were grouped into incipient AC(IAC)or AC cohorts based on hemodynamic status.Demographic profi les,etiologies,clinical presentations,and laboratory results were analyzed.RESULTS:Forty-three AI patients were identifi ed.The population-standardized admission rate for AI increased from 9 to 16 per million person-years,with PAI cases doubling during this period.Adrenal tuberculosis(58.1%)and adrenal hematoma(18.6%)were the leading etiologies.Compared to the IAC group,the AC group demonstrated lower systolic blood pressure(SBP)(P=0.001)and diastolic blood pressure(DBP)(P<0.001);higher neutrophil count(P=0.048),eosinophil count(P=0.044),CRP(P=0.004),blood urea nitrogen(BUN)(P=0.007);lower sodium(P<0.001)and glucose levels(P=0.001).The hospital stay was longer in the AC group(20 d vs.14 d;P<0.001).CONCLUSION:AI incidence is rising in high-altitude regions,with adrenal tuberculosis remaining the most common cause.AC is associated with increased inflammatory responses,hemodynamic instability,and metabolic disturbances.Targeted interventions are required to improve outcomes.
基金Supported by International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2022-MS-02.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.
文摘BACKGROUND Liver injury manifesting as hepatic enzyme abnormalities,has been occasionally identified to be a feature of primary or secondary Addison's disease,an uncommon endocrine disease characterized by adrenal insufficiency.There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease.Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer.CASE SUMMARY A 42-year-old man presented with fatigue and mildly elevated transaminases.Laboratory investigations and imaging studies excluded common etiologies of liver injury.Based on the fact that the patient discontinued long-term therapy with prednisone approximately 2 weeks before he was found to have elevated transaminase levels and the observation that his cortisol was lower than the normal value,he was diagnosed as having hypertransaminasemia secondary to adrenal insufficiency caused by glucocorticoid withdrawal.The patient was infused intravenously with compound diisopropylamine dichloroacctate and compound glycyrrhizin,and his transaminase levels returned to normal after 1 week.Approximately 2 years later,the patient received hydroprednisone treatment for 2 days in an endoscopic sinus surgery.Eight days after he discontinued the hydroprednisone treatment,he developed symptoms reminiscent of glucocorticoid withdrawal syndrome.These symptoms resolved spontaneously after 1 week.Intriguingly,the patient did not develop hepatic dysfunction this time.CONCLUSION The present case,showing some unusual clinical features,highlights the importance of education of clinicians and patients to avoid improper discontinuation of glucocorticoid therapy and complete history taking for prompt recognition.
文摘BACKGROUND Adrenal ectopia is a rare condition in which adrenal tissue is found in an abn-ormal location,often posing diagnostic challenges.Although generally considered benign,it can present as hepatic or other organ lesions,mimicking malignant tumors.In the liver,ectopic adrenal tissue can closely resemble hepatocellular carcinoma or metastatic disease,potentially leading to unnecessary aggressive treatments such as surgery or chemotherapy.Consequently,a high index of sus-picion is essential to avoid misdiagnosis and ensure appropriate management.CASE SUMMARY In this case report,we present a 53-year-old male with ectopic adrenal tissue in the liver,mimicking a potential hepatic malignancy.Based on computed tomo-graphy and magnetic resonance imaging findings,which suggested a malignant liver lesion and a left adrenal adenoma,the patient underwent laparoscopic partial hepatectomy under general anesthesia.Intraoperatively,no signs of liver cirrhosis were observed.An intraoperative ultrasound identified a 1.2 cm hypo-echoic nodule in segment 7 of the liver.Dissection of the right adrenal gland revealed that the nodule had infiltrated the hepatic parenchyma,confirming the presence of ectopic adrenal tissue.Frozen section pathology revealed proliferating adrenal tissue.The patient recovered smoothly and was discharged 10 days post-operatively.CONCLUSION This case report underscores the importance of considering adrenal ectopia in the differential diagnosis of liver lesions,especially when imaging findings suggest malignancy.
文摘We present the diagnostic performance of[18F]Fluorodeoxyglucose positron emission tomography(FDG PET)for adrenal incidentalomas based on lesion size and unenhanced computed tomography(CT)density in Hounsfield units(HU),following current literature and guidelines.A 20 HU cutoff can be applied to differentiate potentially benign from malignant lesions,particularly in ruling in or out adrenocortical carcinoma.While FDG PET provides valuable metabolic information,its likelihood ratios for a positive(LR+)or negative(LR-)result do not exceed the robust diagnostic thresholds of>10.0 or<0.1,respectively.This suggests that positron emission tomography alone is insufficient for definitive characterization and should be integrated with CT or magnetic resonance imaging to leverage their complementary anatomical and functional imaging strengths for optimal diagnostic accuracy.
文摘The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.
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Glucocorticoids(GCs)such as prednisolone are widely used in conditions like nephrotic syndrome,asthma,and autoimmune diseases.However,prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal(HPA)axis,leading to secondary adrenal insufficiency(AI).This condition occurs when the adrenal glands fail to produce adequate cortisol,which is essential for regulating metabolism,immune response,and stress adaptation.Corticotropin-releasing hormone(CRH)from the hypothalamus stimulates the pituitary to release adrenocorticotropic hormone(ACTH),which then triggers cortisol production in the adrenal glands.Prolonged GC use disrupts this system by inhibiting CRH and ACTH secretion,leading to adrenal atrophy and reduced cortisol production.HPA axis suppression is primarily diagnosed through dynamic tests.Early morning cortisol levels above>18 ng/mL typically indicate normal function,while levels<3 ng/mL suggest AI.Intermediate values require additional testing,such as the insulin tolerance test,ACTH stimulation test,and metyrapone test.Prednisolone in nephrotic syndrome suppresses the HPA axis,heightening AI risk,influenced by dose,duration,and timing of administration.Careful GC management is essential to balance disease control with risks of HPA axis suppression.Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients.
基金supported by the National Natural Science Foundation of China(82372624 to X.J.)Guangdong Basic and Applied Basic Research Foundation(2024A1515013102 and 2022A1515012430 to X.J.)The funders had no role in study design,data collection and interpretation,or the decision to submit the work for publication.
文摘Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.
文摘Effects of Mingzhu Oral Liquid on the Hypothalamic-Pituitary-Adrenal Axis in Rats with Liver-Kidney Yin Deficiency WANG Yi-ting1,ZHAO Yang1,ZHU Fei-ya1,WANG Si-qiong1,ZHU Ling-lei1,LI Tao2,TANG Min-ke1,1.Beijing University of Chinese Medicine,Beijing,100029,China 2.Guangzhou Yitong Technology Co.,Ltd.,Guangzhou,510653,China【ABSTRACT】Objective:This study aimed to observe the effects of Mingzhu Oral Liquid on the hypothalamic-pituitary-adrenal(HPA)axis in rats with“liver-kidney yin deficiency”,in order to provide scientific research support for its clinical application in treating related disorders.Methods:A“liver-kidney yin deficiency”model was established in male Sprague-Dawley(SD)rats using a combination of chronic restraint stress and a single lipopolysaccharide(LPS)challenge.The rats were randomly divided into four groups:a blank control group,a model group,a low-dose Mingzhu Oral Liquid group,and a high-dose Mingzhu Oral Liquid group.The blank control group and model group were given normal saline by gavage,while the treatment groups received respective doses of Mingzhu Oral Liquid.Gavage administration was performed once daily for 30 consecutive days.During this period,all groups except the blank control group were subjected to restraint stress.Following the final gavage,all groups except the blank control received an intraperitoneal injection of LPS.Samples were collected 24 h post-injection.Serum levels of cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP)were measured by enzyme-linked immunosorbent assay(ELISA)to evaluate the model state.The serum concentrations of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),and glucocorticoid(GC)were determined to assess HPA axis activity.Changes in proinflammatory factors[tumor necrosis factor-alpha(TNF-α),interleukin-1 beta(IL-1β)]and the anti-inflammatory factor interleukin-10(IL-10)were also measured.Results:One week into the experiment,the weight gain rate slowed in all stress groups.By the end of the experiment,the body weight of these groups was significantly lower than that of the blank control group.Biochemical and hematological analyses revealed that the model group exhibited a significant decrease in lymphocyte count,an increased cAMP/cGMP ratio,reduced activities of glutathione S-transferase(GST)and glutathione transferase(GLT),elevated levels of blood urea nitrogen(BUN)and serum creatinine(Scr),increased serum contents of TNF-αand IL-1β,and a decreased content of IL-10.These findings confirmed the successful establishment of the rat model.Although the body weight of animals treated with Mingzhu Oral Liquid remained lower than that of the normal group,the treatment improved weight gain compared to the model group.Furthermore,Mingzhu Oral Liquid administration increased lymphocyte count,decreased the cAMP/cGMP ratio,restored GST and GLT activities,reduced BUN and Scr levels,lowered serum TNF-αand IL-1βcontents,and increased IL-10 levels,indicating a significant ameliorative effect on the deficiency symptoms.Additionally,serum levels of CRH,ACTH,and GC were elevated in the model rats,suggesting HPA axis hyperactivity.Treatment with Mingzhu Oral Liquid reduced the serum concentrations of these hormones,significantly alleviating the excited state of the HPA axis in stressed rats.Conclusion:Mingzhu Oral Liquid significantly improves the abnormal overall physical signs,blood biochemical parameters,and systemic inflammation in rats with“liver-kidney yin deficiency.”These therapeutic effects may be associated with the corrective action of Mingzhu Oral Liquid on the dysfunctional HPA axis in this model.
文摘Objective: To inquire into diagnosis, and treatment of virilizing andfeminizing a-drenal syndrome, differential diagnosis between benign and malignant sex hormoneproducing adrenal neo-plasma and, treatment principles of congenital adrenal hyperplasia (CAH).Methods: Eight cases of CAH and 5 cases of sex hormone producing adrenal neoplasma were admitted tohospital during 1986-1996. The former included 3 rare cases of 17 a hydroxylase deficiency. Thelatter included 3 cases of feminizing adrenal tumor and 2 cases of virilizing adrenal tumor.Results: Weight, size and CT of the tumor, DHEA, 17 -ks, sex hormone levels, infiltration, andmetastasis were closely related to the degree of differentiation of the tumors. Conclusion:Virilizing and feminizing adrenal neoplasm were removed surgically by different incisions. Modifiedsubcostal incision was recommended as the best choice for huge adrenal mass. Corticoadrenal hormonetreatment fa CAH should be individualized according to the different types of the disease. Sexhormones were not suitable for children suffering from 17 hydroxylase deficiency before puberty.
文摘1病例简介肾上腺黑色腺瘤(adrenal black adenoma)又称色素性肾上腺皮质腺瘤(pigmented adrenocortical adenoma),属于一种罕见的肾上腺良性肿瘤[1]。因其细胞内含大量脂褐素或黑色素颗粒,肉眼多呈黑色或褐色,临床上常称其为黑色腺瘤。国内外文献报道的仅10余例。我科近期收治表现为库欣综合征的肾上腺黑色腺瘤患者1例,并行腹腔镜肾上腺切除术,手术效果良好。现分析其临床资料报告如下。1病例简介患者,女,60岁,因"发现高血压10年余,查体发现左侧肾上腺腺瘤2天"入院。平素血压最高可至160/100mmHg,不伴夜尿增多。
文摘In order to explore the molecular mechanisms of children adrenal neuroblastoma,and screen biomarkers for early diagnosis of this disease,the comparative proteomics were done in this report.The total proteins in children adrenal neuroblastoma and adrenal control tissues were extracted separately and then separated by 2-DE individually.The protein spots were identified eventually by UPLC-HD-MS.In this research,18 difference proteins including stathmin 1 were found.
