Effects of repetitive transcranial magnetic stimulation on hypothalamic-pituitary-adrenal axis of patients with depression

Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）

Shizhenqing granule stimulates the hypothalamic-pituitary-adrenal axis and reduces serum pro-inflammatory factors in a rat model with chronic eczema

Objective:In this study,we examined the effects of Shizhenqing granule(SZQG)on hypothalamicpituitary-adrenal(HPA)axis and serum inflammatory factors in a rat model of chronic eczema,in order to explore the mechanism of action of SZQG in treatment of this disease.Methods:Sixty SpragueeDawley male rats were randomly divided into six groups(with 10 rats per group):blank group;model group;positive control group(prednisone);and the low-,medium-,and high-dose SZQG groups.Except for the blank group,rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema.These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model,and samples were collected 12 h after the last administration.The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH),cortisol(CORT),interleukin(IL)-4,interferon(IFN)-g,IL-25,and IL-31 among the groups were compared.Results:SZQG effectively increased the levels of CRH,ACTH,and CORT,which decreased in the serum of rats with chronic eczema,stimulated the function of the HPA axis,and promoted the expression of glucocorticoids.SZQG reduced the serum levels of inflammatory factors including IL-4,IL-25 and IL-31,which were overexpressed in rats with chronic eczema,and increased those of anti-inflammatory factor IFN-g,thereby alleviating the inflammatory symptoms and itching,and ameliorating the clinical symptoms of chronic eczema.Conclusion:SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.

Seasonal photoperiodic influence of pineal melatonin on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in male rats

Background: Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.Methods: Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were randomly divided into normal control group, sham operation group, and pinealectomized group. The seasonal changes in corticotropin-releasing hormone(CRH),adrenocorticotropic hormone(ACTH), corticosterone, hypothalamic melatonin receptor(MTR), and hippocampal corticosterone receptor(CORTR) were examined by enzyme-linked immunosorbent assay.Results: Comparing the same group between different seasons, we showed that in the normal control group, CRH, ACTH, corticosterone, and MTR were higher, while CORTR was lower in autumn and winter than in spring(all P <.05). Compared with the normal control group, the pinealectomized group showed higher levels of corticosterone(P =.01), MTR(P =.01), and CORTR(P =.03) during spring;reduced levels of MTR and CORTR(both P <.001) during summer;higher levels of ACTH(P =.001) and MTR(P <.001),and lower levels of CRH(P =.001), corticosterone(P <.001), and CORTR(P =.003) during autumn;and lower levels of CRH(P <.001) and MTR(P =.004), and higher level of ACTH(P <.001) in winter.Conclusions: Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin,resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor, which may be the pathophysiological basis for the onset of seasonal affective disorder.

Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats:a potential role of the hypothalamic-pituitary-adrenal axis

OBJECTIVE:To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal(HPA)axis via regulating the expression of glial fibrillary acidic protein(GFAP)in the hippocampus of acute myocardial ischemia(AMI)rats.METHODS:Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups:Sham,AMI(Model),electroacupuncture at Shenmen(HT7)-Tongli(HT5)segment(EA),non-acupoint electroacupuncture(Control),and Model+corticosterone(Model+CORT).AMI was induced via occlusion of the left anterior descending coronary artery,followed by 3 d of electroacupuncture at Shenmen(HT7)-Tongli(HT5)segment.In the Control group,electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail.The AMI+CORT group was injected with CORT(20 mg/kg)in saline.Hemorheology,electrocardiography(ECG),hematoxylin and eosin staining,and expression of glycogen phosphorylase BB(GPBB)and heart-type fatty acid-binding protein(H-FABP)were used to assess cardiac function.The effects of adrenocorticotropic hormone(ACTH)and CORT were evaluated by enzymelinked immunosorbent assay.Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis.Protein expression was evaluated by Western blotting(vimentin and GFAP)and immunofluorescence staining(GFAP).RESULTS:Compared with the Sham group,the hemorheology indicators,heart rate,ECG-ST segment elevation,and GPBB and H-FABP levels were higher in Model rats.The EA group showed reductions in these indicators compared with the Model group.Similarly,in Model rats,the expression of ACTH and CORT were significantly increased compared with the Sham group.The EA group also showed reduced expression of ACTH and CORT.Importantly,proteomics analysis showed that vimentin was differentially expressed in Model rats.Compared with the Sham group,vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI+EA group.Additionally,intraperitoneal injection of CORT aggravated the expression of GPBB,H-FABP and GFAP.CONCLUSIONS:Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity,and that hippocampal GFAP may play an important role in the regulation.

Functional changes in the hypothalamic-pituitary-adrenal axis after successful cardiopulmonary resuscitation

Background:Cardiac arrest(CA)is a terminal event that results in a range of pathophysiological changes in the body,most notably,systemic ischemia-reperfusion injury.The hypothalamic-pituitary-adrenal(HPA)axis is an important neuroendocrine system that modulates adrenocortical hormone release.This study was designed to investigate the changes in HPA-related hormone levels after successful cardiopulmonary resuscitation(CPR)and to explore possible etiologies to provide a basis for relevant clinical research.Methods:We collected the clinical data of 96 patients with CA admitted to the Emergency Department of Beijing Chaoyang Hospital,Capital Medical University,between January 2016 and May 2017.Serum samples were collected 6,24,and 72 hours after restoring spontaneous circulation(ROSC).The data were compared with those of the healthy control group(n=50).An enzyme-linked immunosorbent assay(ELISA)was performed to measure copeptin,adrenocorticotropic hormone(ACTH),corticotropin-releasing hormone(CRH),and total cortisol.Demographic data were collected for both groups.For the CPR group,clinical data and the end-of-study cerebral performance category(CPC)were analyzed.Patients were followed up through day 28.Death or survival after day 28 was used as the study endpoint.Simple values were expressed as medians and quartiles or ratios(%)for statistical analysis.Continuous variables are expressed as mean±standard deviation.Categorical variables were expressed as frequencies and percentages.The mean values of normally distributed measurement data were analyzed using 1-way analysis of variance(ANOVA)for among-group comparisons and the least significant difference(LSD)test for between-group comparisons.SPSS v17(SPSS,Chicago,IL,USA)was used for statistical analysis,and P<0.05 was considered statistically significant.Results:No significant between-group differences were observed in terms of age or sex.The 28-day mortality rate in the CPR group was 71%.ACTH and CRH levels were significantly lower in the CPR group than in the healthy control group(P<0.001).Copeptin and cortisol levels 6 hours after ROSC were significantly higher in the CPR group than in the healthy control group(P<0.001).No significant changes in any indicator were observed over time(6,24,and 72 hours after ROSC)(P>0.05).The CPC score was 1–2(good cerebral performance group)in 13 patients,3–4(poor cerebral performance group)in 17 patients,and 5(brain death or clinical death)in 66 patients.Patients with significantly declining ACTH and CRH levels had higher CPC scores(P<0.05);however,no significant differences were found in other indicators(P>0.05).Conclusion:After post-CA ROSC,ischemia-reperfusion injury may cause brain damage and HPA axis damage and dysfunction,the severity of which is associated with CPC score.

Essence of"Shen(Kidney)Controlling Bones":Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis

As a traditional concept of Chinese medicine（CM）, the theory of ＂Shen（Kidney） controlling bones＂ has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal（HPA） axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis： cells that comprise bone tissue（osteo-related cells） are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental challenges.In the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and neuroplasticity.The glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic mechanisms.Protein interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive functions.An appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive impairment.Patients with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor expression.This review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive activities.It emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive impairment.This provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

Molecular chaperones in stroke-induced immunosuppression

Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome.Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections,such as urinary tract infections and stroke-associated pneumonia,worsening prognosis.Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains,refolding misfolded proteins,and targeting misfolded proteins for degradation.Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones,cochaperones,and their associated pathways.This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.

Prolonged Adrenal Insufficiency after Unilateral Adrenalectomy for Cortisolic Adenoma

Background: The suppression of the hypothalamic-pituitary-adrenal axis by cortisol-secreting adrenocortical tumors is well recognized and requires peri- and postoperative hydrocortisone substitution. Case Presentation: A 48-year-old female patient with hypertension and progressive weight gain, the clinical signs of hypercorticism motivated a hormonal workup revealing an independent ACTH Cushing’s syndrome: with urinary free cortisol (UFC) at 649 nmol/24h (4× normal), adrenocorticotropin hormone (ACTH) at 1.5 ng/l. The rest of the hormonal workup was not performed due to a lack of financial means. An Adrenal CT scan showed a 4 cm right adrenal adenoma. The patient underwent a right adrenalectomy with an adrenal adenoma on pathological examination. The contralateral side was normal. The patient was treated with hydrocortisone 30 mg/d for 6 weeks then 15 mg/d, during the monitoring we noted a persistence of the adrenal insufficiency for now 4 years. Basal cortisol levels during follow-up were very low (<3 μg/dl) ruling out the need for synacthen stimulation tests. Conclusion: Adrenal cortisol tumors are recognized by suppression, the duration of hypothalamic-pituitary-adrenal axis suppression is variable from 11 to 60 months depending on the series, which depends on the duration, severity of hypercortisolism, tumor size and other unknown factors. A longer follow-up of these patients is necessary to look for recovery of the contralateral adrenal gland.

Advances in glucocorticoid-mediated stroke-associated immunosuppression

Acute ischemic stroke is often accompanied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mechanism to prevent an excessive inflammatory response. Glucocorticoid,an important product of the hypothalamic-pituitary-adrenal axis,plays a crucial role in inducing immunosuppression in the early stage of acute cerebral infarction. Glucocorticoid not only affects the secretion of inflammatory cytokines but also influences the function of immune cells,ultimately leading to an increased risk of infection.

短链脂肪酸-酰化淀粉对小鼠抑郁样行为的缓解及机制

大量研究证实“微生物-肠-脑轴”在抑郁症的发生发展中发挥重要作用,而肠道微生物产生的短链脂肪酸(short chain fatty acids,SCFAs),更是参与神经调控作用的关键分子。该研究首次采用SCFA-酰化淀粉在大肠定点释放5类短链脂肪酸,探究其对慢性应激诱导的抑郁症状的缓解及机制。以雄性C57BL/6 J小鼠为研究对象,通过为期5周的慢性不可预知温和应激构建抑郁小鼠模型,通过旷场实验、高架十字迷宫实验和强迫游泳实验对小鼠的抑郁样行为进行评价。同时对小鼠应激激素、神经递质水平及相关酶的表达水平进行检测。结果显示,乙酸、异丁酸和丁酸能在不同程度上减轻小鼠抑郁样行为,其可能机制与SCFAs修复下丘脑-垂体-肾上腺轴反馈调节障碍、恢复5-羟色胺的正常代谢相关。该研究为抑郁症的营养干预提供了新的理论依据。

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome

Irritable bowel syndrome(IBS)is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role.The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors,interacting with peripheral/central neuroendocrine and immune changes,may induce symptoms of IBS,modulate symptom severity,influence illness experience and quality of life,and affect outcome.The present review focuses on the role of negative affects,including depression,anxiety,and anger,on pathogenesis and clinical expression of IBS.The potential role of the autonomic nervous system,stress-hormone system,and immune system in the pathophysiology of both negative affects and IBS are taken into account.Psychiatric comorbidity and subclinical variations in levels of depression,anxiety,and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS,such as sensorimotor functions,gut microbiota,inflammation/immunity,and symptom reporting.

Molecular mechanism of noradrenaline during the stress-induced major depressive disorder

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

Is perinatal neuroendocrine programming involved in the developmental origins of metabolic disorders?

The discovery that small size at birth and during infancy are associated with a higher risk of diabetes and related metabolic disease in later life has pointed to the importance of developmental factors in these conditions. The birth size associations are thought to refl ect exposure to adverse environmental factors during early development but the mechanisms involved are still not fully understood. Animal and human work has pointed to the importance of changes in the setpoint of a number of key hormonal systems controlling growth and development. These include the IGF-1/GH axis, gonadal hormones and, in particular, the systems mediating the classical stress response. Several studies show that small size at birth is linked with increased activity of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in adult life. More recent human studies have shown associations between specif ic adverse experiences during pregnancy, such as famine or the consumption of adverse diets, and enhanced stress responses many decades later. The mediators of these neuroendocrine responses are biologically potent and are likely to have a direct infl uence on the risk of metabolic disease. These neuroendocrine changes may also have an evolutionary basis being part of broader process, termed phenotypic plasticity, by which adverse environmental cues experienced during development modify the structure and physiology of the adult towards a phenotype adapted for adversity. The changes are clearly advantageous if they lead to a phenotype which is well-adapted for the adult environment, but may lead to disease if there is subsequent overnutrition or other unexpected environmental conditions.

Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient:A case report

BACKGROUND Pneumocystis jiroveci pneumonia(PJP)is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy.In non-human immunodeficiency virus-infected patients,the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments.The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care.CASE SUMMARY We report a case of PJP in the perioperative period.A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5(MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and cyclosporine.The patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral head.She was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative day.On the fifth day after surgery,the patient suddenly developed dyspnea.The computed tomography scan showed diffuse grid shadows and ground glass shadows in both lungs.Polymerase chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis jiroveci.The patient was eventually diagnosed with PJP and was administered with oral trimethoprim-sulfamethoxazole.At the 6-mo review,there was no recurrence or progression.CONCLUSION Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

Xylocarpin H, a Limonoid of <i>Xylocarpus granatum</i>, Produces Antidepressant-Like Activities in Mice

Major depression is a common psychiatric disorder worldwide that imposes a substantial health burden on society. Currently available antidepressants do not meet the clinical needs. Here, we report that Xylocarpin H, a limonoid of Xylocarpus granatum, has antidepressant-like effects in mouse forced swimming and tail suspension tests, two validated models of depression. 7-day oral administration of Xylocarpin H resulted in dose-dependent decreases immobility duration within the dose range of 15 - 50 mg/kg. Xylocarpin H dose-dependently increases the time spent in the central zone at doses of 5 - 50 mg/kg in locomotion activity test. In addition, 7-day treatment Xylocarpus H at 15 and 50 mg/kg doses significantly decreases levels of serum corticosterone and adrenocorticotropic hormone (ACTH) following the acute stress of forced swimming test. Furthermore, these effective doses of Xylocarpin H do not affect locomotor activity and levels of serum corticosterone and ACTH in the absence of stress. In summary, the present study, for the first time, demonstrates that Xylocarpin H exerts antidepressant-like effects in mouse behavioral models of depression, likely by inhibiting HPA axis systems. These data provide primarily basis for developing Xylocarpin H as a novel antidepressant candidate for the treatment of depression and stress related disorders.

LW-AFC,a new traditional Chinese medicine formula,shows promising therapeutic effects on Alzheimer disease

Alzheimer disease(AD) is the leading cause of dementia that affects millions of elderly people worldwide.The currently available therapies have limited efficacy. Liuwei Dihuang decoction(LW),a classical traditional Chinese medicine(TCM) formula,has long been used to treat various diseases,including dementia. A large number of pharmacological studies have showed that LW has beneficial effects on AD. LW-AFC is a new formula consisted of the main active components prepared fromLW.In this study,we found that administration of LW-AFC significantly improved behavioral performances in spontaneous locomotor activity,object recognition memory,spatial learning and memory,passive and active avoidance impairment in some AD mouse models,such as SAMP8 and APP/PS1 transgenic mice. Meanwhile,the impairments of long-term potentiation(LTP) were significantly ameliorated by LW-AFC administration in SAMP8 mice,as well as in corticosterone-induced LTP inhibition mice model.These effects were companied by alleviating of the neuron loss in the hippocampus,suppressing of A-beta deposition in the brain,and reducing of the concentration of Abeta42 in the hippocampus and plasma of APP/PS1 mice. The restoring and correcting of imbalance of hypothalamic-pituitary-adrenal(HPA) and hypothalamic-pituitary-gonadal(HPG) axis,the disorder of lymphocyte subsets,the abnormality of production of cytokine were also observed in LW-AFC treated SAMP8 and APP/PS1 mice.These findings indicated that LW-AFC ameliorated the behavioral and pathological deterioration of AD mice via the restoration of the NIM network in a holistic way,suggesting that LW-AFC might bea promising therapy for AD.