Serum Norepinephrine Research Articles

Acupuncture at stellate ganglion combined with western medication for orthostatic hypotension in Parkinson's disease: a randomized controlled trial

To observe the effect of acupuncture at stellate ganglion on orthostatic hypotension (OH) in Parkinson's disease (PD), and explore its action mechanism. A total of 68 patients with OH in PD were randomly divided into a combination group (34 cases, 2 cases dropped out, 1 case was eliminated) and a western medication group (34 cases, 1 case was eliminated). Both groups received stable dose anti-PD western medication, the western medication group received oral midodrine hydrochloride tablets, 2.5 mg each time, 2 times a day. The combination group was treated with acupuncture at bilateral stellate ganglion on the basis of the western medication group, without retaining needles, once a day, 5 times a week. Both groups were treated for 2 weeks. Supine and orthostatic blood pressure, orthostatic hypotension questionnaire (OHQ) score, TCM syndrome score, unified Parkinson's disease rating scale (UPDRS) score before and after treatment in the two groups were observed, the level of serum norepinephrine (NE) was detected, and the clinical effect was evaluated. After treatment, orthostatic systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the combination group were increased compared with those before treatment (P<0.01), OHQ score, TCM syndrome score, UPDRS score were decreased compared with those before treatment (P<0.01); supine SBP in the western medication group was increased compared with that before treatment (P<0.05), OHQ score was decreased compared with that before treatment (P<0.05); the levels of serum NE in both groups were increased compared with those before treatment (P<0.01). After treatment, orthostatic SBP, orthostatic DBP and the level of serum NE in the combination group were higher than those in the western medication group (P<0.01, P<0.05), the OHQ score, TCM syndrome score, UPDRS score were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 87.1% (27/31) in the combination group, which was higher than 63.6% (21/32) in the western medication group (P<0.05). Acupuncture at stellate ganglion can increase the orthostatic blood pressure in patients with OH in PD , improve clinical symptoms, and the mechanism may be related to the up-regulation of NE.

Activated sympathetic nerve post stroke downregulates Toll-like receptor 5 and disrupts the gut mucosal barrier

The gut permeability significantly increases after ischemic stroke, partly due to disrupted mucosal barrier, but the mechanism remains elusive. Here, we found that the mucus disruption starts at 2h post stroke, whereas goblet cell functions remain intact. Meanwhile, the flagellated bacteria Helicobacter thrives and penetrates in the mucus layer. Elimination of the mucosal microbiota or transplantation of Helicobacter in germ-free mice reveals an important role of the mucosal microbiota in mucus disruption. The bacterial invasion is due to downregulated Toll-like receptor 5 (TLR5) and its downstream products flagellin-specific IgA and antimicrobial peptides. Knockdown of intestinal TLR5 increases the abundance of flagellated bacteria and exacerbates mucus injury. Intestinal TLR5 is downregulated by the activation of sympathetic nerve. Serum noradrenaline level is positively associated with flagellin level in patients with stroke and patients' prognosis. These findings reveal a neural pathway in which the sympathetic nerve disrupts the mucosal barrier, providing potential therapeutic targets for stroke injury.

Benzo[a]pyrene exposure induces anxiety-like behaviors in the mice through brain metabolic alterations

The deleterious health impacts of polycyclic aromatic hydrocarbons (PAHs) on the population have been extensively substantiated and acknowledged. Mounting evidence underscores that PAH exposure is closely linked to an elevated risk of mental disorders, particularly in populations experiencing occupational and high-level exposure. In this study, we aimed to investigate the mechanisms underlying anxiety-like behaviors induced by different dosages of PAHs, with a concentrated focus on brain region-specific metabolic alterations in mice using various metabolomics approaches. Male C57BL/6 mice were exposed to benzo[a]pyrene (B[a]P), a typical PAH, through gavage at occupational exposure and EPA toxicologically relevant dosages (2.0 and 20.0 mg/kg/day) for 21 days, respectively. Behavioral assessments revealed that occupational exposure to B[a]P induced anxiety-like behaviors in C57BL/6 mice. Meanwhile, elevated serum norepinephrine and corticotropin-releasing hormone further confirmed the anxiety-inducing effects of B[a]P exposure. Metabolomics analysis uncovered dysregulation across various metabolic pathways following B[a]P exposure, encompassing brain neurotransmitter, organic acid, amino acid, lipid, fatty acid, and cholesterol. Anxiety levels and lipid metabolic abnormalities were notably exacerbated at the higher dosage, despite being only a 10-fold increase. Of particular significance, a decrease in lysophosphatidic acid (LPA) and lysophosphatidylserine (LPS) emerged as pivotal indicators of B[a]P neurotoxicity. Spatial-resolved metabolomics further demonstrated distinctive lipid and metabolite profiles across different brain subregions after exposure to B[a]P. Remarkably, alterations were specifically observed in the anxiety-related brain regions, such as the hippocampus, cortex, white matter, and thalamus, varying with exposure dosages. These findings underscore the significance of brain metabolic abnormalities in the development of mental disorders triggered by B[a]P exposure and highlight the need for establishing precise exposure limits of B[a]P to safeguard public mental health.

Abstract P168: The Unholy Link: The Herbicide Glyphosate Contributes to Hypertension, Gut Microbiota Dysbiosis, and Sympathetic Overdrive

Introduction: Glyphosate, marketed as Roundup®, is a widely used potent herbicide in the US. Glyphosate inhibits 5-enolpyruvylshikimate-3-phosphate synthase of the shikimate pathway, a non-mammalian signaling pathway present in plants and microbes. Therefore, glyphosate has been deemed safe for humans. However, humans are holobionts with symbiotic gut microbiota susceptible to gut dysbiosis when exposed to glyphosate. Because gut microbiota is an important contributor to hypertension (HTN), we hypothesized that exposure to glyphosate leads to gut dysbiosis and HTN. Methods: Dahl salt-sensitive (S) rats were administered either vehicle or glyphosate (175 mg/kg/day) in drinking water for three weeks ad libitum. In one group of rats (N=4/group), sympathetic nerve activity was assessed using in situ whole nerve recordings and by measuring circulating norepinephrine (NE) levels by ELISA. In separate rats (N=6–8/group), blood pressure (BP) was measured once a week for three weeks by radiotelemetry, and circulating NE was determined by ELISA. At the endpoint, fecal microbiome analyses were performed using the Illumina and Oxford Nanopore platforms. Results: Exposure to glyphosate for just one week was sufficient to significantly increase systolic (173 mmHg vs 160 mmHg, p&lt;0.0001) and mean arterial pressure (MAP) (148 mmHg vs 141 mmHg, p&lt;0.0002), but not diastolic BP of S rats. Through week three, BP continued to rise in glyphosate-treated rats with greater differences in the systolic (195 mmHg vs 176 mmHg, p&lt;0.0001), diastolic (142 mmHg vs 135 mmHg, p&lt;0.0001), and MAP (168 mmHg vs 155 mmHg, p&lt;0.0001). This was accompanied by increased sympathetic nerve activity and serum NE as early as one week of exposure to glyphosate (5.85 ng/mL vs 4.77 ng/mL, p&lt;0.001), which continued at week three of glyphosate exposure (13.31 ng/mL vs 6.16 ng/mL, p&lt;0.001), indicative of adrenergic overdrive. 16S data showed that glyphosate altered the composition of commensal gut microbiota, reducing bacterial α-diversity (Shannon entropy; p&lt;0.05) and β-diversity (Bray-Curtis; p&lt;0.02). Whole metagenomic analysis revealed a higher abundance of several bacterial species, including Candidatus spp., Erysipelaclostridium ramosum , and Clostridium sporogenes in the glyphosate-treated rats. Conclusions: Glyphosate exposure elevated BP, increased sympathetic nerve activity, and altered gut microbiota composition. This is the first proof-of-concept study to demonstrate that glyphosate contributes to HTN.

Influence of humanistic care-based operating room nursing on safety, recovery, and satisfaction after radical surgery for colorectal carcinoma

BACKGROUND Radical surgery is a preferred treatment for colorectal carcinoma, wherein nursing intervention is essential for postoperative recovery and prevention of complications. Recently, the application of humanistic care in medical care has attracted attention. Humanistic care emphasizes comprehensive care, with importance attached to patients’ physical needs as well as psychological and emotional support to provide more humane and personalized care services. However, no clinical reports have examined the use of humanistic care in patients undergoing radical surgery for colorectal carcinoma. AIM To investigate the influence of humanistic care-based operating room nursing on the safety, postoperative recovery, and nursing satisfaction of patients who have undergone radical surgery for colorectal carcinoma. METHODS In total, 120 patients with rectal cancer who underwent surgery in Zhongnan Hospital of Wuhan University between August 2023 and March 2024 were selected and grouped based on the nursing methods employed. Of these patients, 55 were treated with routine nursing intervention (control group) and 65 were provided humanistic care-based operating room nursing (research group). The patients’ vital signs were recorded, including systolic/diastolic blood pressure (SBP/DBP) and heart beats per minute (BPM), as well as serum stress indices, including norepinephrine (NE), adrenal hormone (AD), and cortisol (Cor). Postoperative recovery and complications were also recorded. Patients’ negative emotions, life hope, and nursing satisfaction were evaluated using the Self-rating Depression/Anxiety Scale (SDS/SAS), Herth Hope Index (HHI), and self-developed nursing satisfaction questionnaire, respectively. RESULTS During emergence from anesthesia, SBP, DBP, and BPM levels were found to be lower in the research group than those in the control group, also serum Cor, AD, and NE levels were lower. In addition, the research group had shorter operative, awakening, anal exhaust, first postoperative ambulation, drainage tube removal, intestinal recovery, and hospital times. The total complication rate and the SDS and SAS scores were lower in the research group than those in the control group. The HHI and nursing satisfaction scores were higher in the research group. CONCLUSION Humanistic care-based operating room nursing can mitigate physiological stress responses, reduce postoperative complications, promote postoperative recovery, relieve adverse psychological emotions, and enhance life hope and nursing satisfaction in patients undergoing radical surgery for colorectal carcinoma, which can be popularized in clinical practice.

Effects of spinal-epidural anesthesia combined with intravenous etomidate on adrenocortical and immune stress in elderly patients undergoing anorectal surgery: A retrospective analysis.

The management of anesthesia in elderly patients undergoing surgery presents unique challenges, particularly in mitigating stress responses and ensuring stability. Etomidate may alleviate adrenocortical and immune stress. This study aims to investigate the anesthetic effects of combined spinal-epidural anesthesia (CSEA) supplemented with etomidate during anorectal surgery in elderly patients. The medical records of 49 cases treated with CSEA and etomidate (ETO group) and 48 cases treated with CSEA alone (control group) were reviewed and analyzed. All patients received ropivacaine hydrochloride for anesthesia, with the ETO group additionally receiving an infusion of etomidate for sedation. Parameters such as arterial blood gas, visual analog scale (VAS), Ramsay sedation scale (RSS), serum cortisol and norepinephrine levels, pro-inflammatory cytokines, and lymphocyte ratios were assessed at different time points. Compared to the control group, the ETO group showed increased mean arterial pressure, decreased heart rate, and elevated arterial SpO2 30 minutes after anesthesia. The ETO group also had higher RSS scores, lower VAS scores, and reduced serum cortisol and norepinephrine levels. Additionally, decreased levels of pro-inflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-8, were observed, along with an increase in the regulatory cytokine IL-10. An increased proportion of CD4+ T cells and a higher CD4/CD8 ratio were also noted. This study demonstrates the benefits of using etomidate to mitigate adrenocortical and immune stress in elderly patients undergoing anorectal surgery.

Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats.

To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action. The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis. Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons. The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress

BackgroundOlanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive.MethodsKrasLSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines.ResultsIn this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients.ConclusionWe identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Observation on the Effect of Rapid Rehabilitation Nursing with Integrated Medical Care in Perioperative Period of Laparoscopic Appendicitis in Children.

Acute appendicitis is one of the most common causes of acute abdomen in pediatric surgery. The purpose of this study was to observe the effects of integrated rapid rehabilitation nursing in children with laparoscopic appendectomy (LA) during the perioperative period. A total of 200 children with appendicitis who underwent LA in our hospital from January 2022 to January 2023 were retrospectively selected as the study subjects. According to the nursing mode, they were divided into a control group (n = 100) and an observation group (n = 100). The control group was treated with routine nursing intervention, and the observation group was treated with an integrated rapid rehabilitation nursing intervention. Perioperative indices (operation time, first postoperative exhaust time, length of hospital stay) were recorded and compared between the two groups. The visual analog scale (VAS) was used to score the two groups at 6 h, 12 h, 24 h, and 48 h after surgery, and the pain degree of the children was quantitatively evaluated. The levels of serum stress response indices (cortisol (Cor), norepinephrine (NE), and adrenocorticotropic hormone (ACTH)) in the two groups were measured. The incidence of postoperative complications, improvement of postoperative quality of life, and nursing satisfaction were compared between the two groups. The operation time, first postoperative exhaust time, and hospitalization time in the observation group were significantly shorter than those in the control group (p < 0.05), and the VAS scores of the patients in the observation group were lower than those in the control group at each time point of 6 h, 12 h, 24 h, and 48 h after surgery (p < 0.05). One hour after surgery, the serum Cor, NE, and ACTH levels of the two groups of patients were significantly higher than those before surgery, and the levels for the observation group were significantly lower than those of the control group (p < 0.05). After treatment, the quality of life scores of patients in both groups was significantly higher than before treatment, and the quality of life scores of patients in the observation group was significantly higher than that of the control group (p < 0.05). The postoperative complication rate of the observation group was 3.00% (3/100), which was significantly lower than that of the control group (13.00% (13/100)) (χ2 = 6.793, p = 0.009). The nursing satisfaction of the observation group was 95.00% (95/100), which was significantly higher than that of the control group (79.00% (79/100)) (χ2 = 11.317, p = 0.001). The integrated rapid rehabilitation nursing management mode is an intervention that can effectively alleviate the effects of LA on stress reactions and pain in children with appendicitis. It can effectively reduce the incidence of postoperative complications and improve the patient's nursing satisfaction, allowing children with appendicitis to recover as soon as possible after surgery, and can improve patients' quality of life. It helps to improve the overall clinical efficacy, and the treatment process is simple to operate, relatively safe and reliable, has high use value, and is worthy of further promotion in clinical treatment.

VASOPRESSOR REDUCTION EFFECT OF POLYMYXIN B HEMOPERFUSION IN PATIENTS WITH PERITONITIS-INDUCED SEPTIC SHOCK: A PROPENSITY SCORE-MATCHED ANALYSIS.

Background : This study aimed to evaluate the effect of polymyxin B hemoperfusion (PMX-HP) in patients with peritonitis-induced septic shock who still required high-dose vasopressors after surgical source control. Methods : This retrospective study included adult patients admitted to the surgical intensive care unit (ICU) at Seoul National University Hospital between July 2014 and February 2021 who underwent major abdominal surgery to control the source of sepsis. Patients were divided into two groups based on whether PMX-HP was applied after surgery or not. The primary and secondary endpoints were the vasopressor reduction effect, and in-ICU mortality, respectively. Propensity score matching was performed to compare the vasopressor reduction effect. Results : A total of 338 patients met the inclusion criteria, of which 23 patients underwent PMX-HP postoperatively, whereas 315 patients did not during the study period. Serum norepinephrine concentration decreased over time regardless of whether PMX-HP was applied. However, it decreased more rapidly in the PMX-HP(+) group than in the PMX-HP(-) group. There were no significant differences in demographics including age, sex, body mass index, and most underlying comorbidities between the two groups. Risk factors for in-ICU mortality were identified by comparing patient characteristics and perioperative factors between the two groups using multivariate analysis. Conclusion : For patients with peritonitis-induced septic shock, PMX-HP rapidly reduces the requirement of vasopressors immediately after surgery but does not reduce in-ICU mortality. This effect could potentially accelerate recovery from shock, reduce sequelae from vasopressors, and ultimately improve quality of life after discharge.

Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: A randomized controlled trial

Study objectiveTo investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DesignA prospective single center double blinded randomized placebo-controlled trial. SettingPerioperative period; operating room, post anesthesia care unit and hospital ward. Patients129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. InterventionsDuring the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MeasurementsEmotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100β, BDNF, IL-6, acetylcholine, and norepinephrine). Main resultsThe high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100β and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. ConclusionsA single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor.Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.

Processed Polygonatum cyrtonema Hua attenuates postpartum depression in rat model by regulating monoamines and hormones

BackgroundPolygonatum cyrtonema Hua is a traditional Chinese medicinal food herb which can regulate the liver and Qi, nourish the heart and blood, moisten the lungs and nourish the kidneys with the potential to treat emotional diseases. However, few studies have explored the effects of Polygonatum cyrtonema Hua on postpartum depression. Therefore, we investigated whether processed Polygonatum cyrtonema Hua could improve postpartum depression in rat models by regulating monoamines and hormones. MethodsFemale Sprague-Dawley rats were randomized into normal control (0.9%Nacl), Sham operation (0.9%Nacl), postpartum depression model (0.9%Nacl), fluoxetine (2.5 mg/kg Fluoxetine), low, medium and high dose of processed Polygonatum cyrtonema Hua (2.5 g/kg, 5 g/kg, 10 g/kg) groups. Rats in these groups received drug intervention, and then subjected to Open-field test and Forced swimming test. Brain tissues and serum samples were collected and used to quantify levels of monoamines, hypothalamic-pituitary-adrenal axis and serum Estradiol. The status of neuronal cells in hippocampus 1 region was examined through hematoxylin-eosin staining, whereas expression of estrogen receptor α and β was detected by immunohistochemistry. ResultsRats in the model group showed decreased mobility time, the disorder of neuronal cells in hippocampus 1 area, and decreased concentration of 5-hydroxytryptamine and dopamine in brain tissue, norepinephrine and estradiol in serum as well as estrogen receptor α and β expression. They also exhibited increased adrenocorticotropic hormone, corticosterone and corticotropin releasing hormone in serum. However, the treatment with processed Polygonatum cyrtonem Hua or fluoxetine reversed the above abnormalities. ConclusionThe H group showed significant improvement in postpartum depression in rats, and processed Polygonatum cyrtonema Hua can be used as a developing drug for the prevention or treatment of depression.

Perioperative changes of serum orphanin in diabetic patients and its relationship with sympathetic nervous system

The occurrence of cardiovascular events in diabetic patients during the perioperative period is related to the activation of sympathetic nerves. Basic research shows that serum nociceptin/orphanin FQ (N/OFQ) levels in diabetic neuropathy rats increased, and N/OFQ reduces the release of norepinephrine (NE). We hypothesize that N/OFQ will affect the sympathetic nervous system during perioperative myocardium of diabetic patients. 66 patients with unilateral knee arthroplasty were divided into diabetes group (D group) and non-diabetes group (N group). Measured blood glucose, serum NE, N/OFQ concentrations at the 30 min before anesthesia (T0), 1 h after surgery (T1), 24 h after surgery (T2) and the cardiac troponinI (cTnI) concentration at T0 and T2. Compared with N group, the concentration of blood glucose, N/OFQ and cTnI in D group was higher and the NE was lower at T0 (P < 0.05). At T1, the blood glucose, N/OFQ, NE concentrations of D group increased, only the blood glucose increased in N group (P < 0.05). Serum N/OFQ of D group from T0 to T1 was correlated with the change trend of blood glucose, NE concentration from T0 to T1 and cTnI from T0 to T2(r = 0.386, P = 0.027; r = 0.350, P = 0.046; r = 0.363, P = 0.038). The outcomes demonstrated that the preoperative serum N/OFQ concentration in diabetic patients was increased, and the increase in N/OFQ concentration during the operation was related to the increase in NE and cTnI concentrations, perioperative N/OFQ may mediate myocardial injury through sympathetic nervous system.

The Effects of the Dietary Inclusion of By-Products Obtained after the Extraction of Vitamin B2 from Fermented Soybean on the Performance and Meat Quality of Growing–Finishing Pigs

The by-products obtained after the extraction of vitamin B2 from fermented soybean (VBP), primarily consisting of soybean meal, soybean oil, vitamin B2, and Bacillus subtilis, may serve as a cost-effective and recycled resource in animal feed. This research aimed to assess the impact of VBP on the growth performance, nutrient utilization, blood parameters, and meat quality of pigs in the growing–finishing phase. In this 16-week feeding experiment, 140 pigs of mixed breed [Duroc × (Landrace × Yorkshire)] were used, with an initial average body weight of 26.05 ± 1.32 kg. The pigs were assigned randomly to one of four dietary groups, each consisting of five pigs, with two gilts and three barrows per pen, and a total of seven repetitions per treatment. The animals were fed different levels of by-products after vitamin B2 extraction (0, 10, 20, and 30 g/kg as the CON, VBP10, VBP20, and VBP30 dietary groups, respectively) in a three-phase feeding trial (wk. 0–4, 4–8, and 8–13). When higher levels of VBP were added as supplements, the outcomes indicated that there were no notable variations (p &gt; 0.05) in growth performance and nutrient digestibility among the treatment groups throughout the trial. In phase II (4–8 weeks), the inclusion of VBP in the diets showed a reduction (p = 0.011; with linear and quadratic effects, p = 0.003) in serum norepinephrine concentration. The sensory evaluation of meat color was linearly improved (p = 0.043) in pigs fed with graded levels of VBP supplementation. The percentage of lean meat showed a significant improvement (p = 0.016) with the gradual levels of VBP supplementation. The addition of 30 g/kg (on an as-fed basis) of vitamin B2 by-products in the diet can simultaneously mitigate the negative impacts of acute stress without compromising growth performance and enhance the percentage of lean meat. These findings suggest that VBP could be a viable and economical alternative to corn and soybean meal and partially replace it in pig feed.

Effects of regulator of G protein signaling 2 (RGS2) overexpression in the paraventricular nucleus on blood pressure in rats with angiotensin II-induced hypertension.

The hypothalamic paraventricular nucleus (PVN) regulates sympathetic activity and blood pressure. The regulator of G protein signaling 2 (RGS2) is a negative G protein regulator, which selectively regulates G⍺q signaling, a potential cause of hypertension. This study aimed to examine angiotensin II (ANG II)-G protein-RGS2 signaling on the central mechanisms of blood pressure control, sympathetic activation, and kidney function. The Sprague Dawley rats were infused with ANG II (200ng/kg/min) via osmotic mini pump to induce hypertension. Adenovirus (AV) vectors encoding RGS2 was transfected into the PVN in vivo. By radio telemetry measurements, we found AV-RGS2 transfection to the PVN significantly attenuated the increase of mean arterial pressure in ANG II infusion rats from days 2-7 of the 2-week experiment (Day 7: ANG II + AV-RGS2 141.3 ± 10.0mmHg vs. ANG II 166.9 ± 9.3mmHg, p < 0.05). AV-RGS2 transfection significantly reduced the serum norepinephrine level and acute volume reflex and increased daily urine volume and sodium excretion in ANG II-infused hypertensive rats. AV-RGS2 transfection significantly reduced G⍺q and PKC protein expressions within the PVN in ANG II infusion rats. In cultured mouse hypothalamic cells, real-time PCR study showed ANG II treatment increased mRNA expression of G⍺q, G⍺s, and RGS2, and AV-RGS2 treatment decreased ANG II-induced mRNA expression of G⍺q and G⍺s. Using confocal imagery, we found that AV-RGS2 attenuated the increase of calcium influx in ANG II-treated cells. Our results suggest that central overexpression of RGS2 in the PVN attenuated the increase of blood pressure and sympathetic outflow, and improves kidney excretory function in hypertensive rats. This may be via the alteration of ANG II-G-protein-RGS2 signaling in the central nervous system.

Targeted ablation of the left middle cervical ganglion prevents ventricular arrhythmias and cardiac injury induced by AMI.

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapytargeting LMCG represented a promising strategy for the treatment of AMI.

Effectiveness of Calcium Alginate Dressing in Combination with Nasal Endoscopic Bipolar Electrocoagulation and Low-Temperature Plasma Knife Treatment on Bleeding Volume, Nasal Ventilation, Stress Response, and Recurrence Rate in Patients with Refractory Epistaxis

The aim of this study was to compare the effects of nasal endoscopic bipolar electrocoagulation (BE) and low-temperature plasma knife (LPK) treatment on intractable epistaxis (IE) in order to provide a reference and guidance for future treatment options for IE. A total of 109 patients with IE admitted to Dongying People’s Hospital from June 2021 to May 2022 were selected for the study. Of these, 58 were treated with BE (BE group) and 51 were treated with LPK (LPK group). The nasal cavities of patients in the BE and LPK groups were filled with a gelatin sponge and calcium alginate dressing, respectively, after surgery. The clinical efficacy, operation time, hemostasis time, and intraoperative bleeding volume of the two groups were compared. Patients’ unilateral inspiratory resistance (IR), expiratory resistance (ER), bilateral total inspiratory resistance (TIR), and total expiratory resistance (TER) were measured using a nasal resistance tester, and pain was assessed using a visual analog scale (VAS). Serum epinephrine (E), norepinephrine (NE), and cortisol (Cor) levels were also measured in patients before and after surgery, and complications were recorded. The recurrence of IE was measured at a 6-month follow-up after discharge from the hospital. There were no differences in clinical efficacy, hemostasis time, or intraoperative bleeding between groups (P &gt;0.05), and the operative time was longer in both BE groups (P &lt;0.05). In addition, postoperative IR, ER, TIR, and TER were higher in the BE group than in the LPK group, and the VAS score results were also higher at 1 d postoperatively (P &lt;0.05). After surgery, E, NE, and Cor were elevated in both groups; more so in the BE group than in the LPK group (P &lt;0.05). Differences in the incidence of complications and prognostic recurrence rates between groups were not statistically significant (P &gt;0.05).

A RARE PRESENTATION OF SMALL CELL LUNG CARCINOMA METASTASIZING TO PHEOCHROMOCYTOMA

Abstract Introduction/Objective Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another unrelated tumor. We report an interesting case of a tumor-to-tumor metastasis of small cell lung carcinoma to pheochromocytoma of the adrenal gland. Methods/Case Report A 75-year-old female former cigarette smoker with a past medical history of hypertension presented with a two-day history of dyspnea and epigastric pain. Physical examination demonstrated elevated blood pressure only. A computerized axial tomography scan of the chest and abdomen showed an incidental 3.1 cm right adrenal mass and right hilar lymphadenopathy. Detailed biochemical workup showed elevated serum epinephrine, norepinephrine, and 24-hour urine metanephrine. Adrenalectomy showed a 5.8 cm tumor mass with solid lobulated yellow to pink-tan and focally hemorrhagic cut surfaces. Microscopic examination showed a neoplasm composed of two distinct components. The predominant component consisted of nests ("zellballen") of large polygonal cells with variable nuclear pleomorphism, abundant amphophilic to basophilic cytoplasm, and a delicate intervening fibrovascular stroma, without significant mitotic activity. The minor component was characterized by sheets and nests of "small blue cells" with round to ovoid nuclei, stippled nuclear chromatin pattern, scanty cytoplasm, patchy necrosis, and high mitotic activity (&amp;gt;20 mitoses per 10 HPF). Foci of small cell carcinoma deposits were also present in the lymphatic channels of pheochromocytoma. Immunohistochemical stains demonstrated cytoplasmic staining of predominant component tumor cells for synaptophysin, chromogranin, and the absence of staining for TTF-1, CK CAM 5.2, and Ki-67. However, minor component tumor cells demonstrated cytoplasmic staining for synaptophysin, membranous staining for CK CAM 5.2, and nuclear staining for TTF-1 and Ki-67(60%). A final diagnosis of composite pheochromocytoma (predominant) and small cell neuroendocrine carcinoma (minor) was rendered. The possibility of a” collision” tumor comprising primary small cell carcinoma of pulmonary origin metastatic to an adrenal pheochromocytoma in light of the patient's cigarette smoking history and the presence of right hilar lymphadenopathy was favored. The subsequent biopsy of the right subcarinal adenopathy showed small cell carcinoma. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, this is the only case of metastasis to a pheochromocytoma from a small cell neuroendocrine lung carcinoma.

Terbutaline Modulates Macrophage Homeostasis and Macrophage-T-Cell Interactions in Immune Thrombocytopenia

Background: Increased platelet destruction by macrophage phagocytosis contributes to immune thrombocytopenia (ITP). Neural immune modulation in autoimmune diseases has been given considerable interest. Our preliminary studies showed a decreased sympathetic innervation in the bone marrow and spleen of ITP mice and that abnormal T cell immunity caused by sympathetic modulation promoted the progression of ITP ( Blood Advances 2019; J Thromb Haemost, 2023). Moreover, previous studies indicated a potential interaction between T cells and macrophages ( Immunity, 2017). However, the regulation of spleen sympathetic denervation on macrophage function and the interaction between splenic macrophages and T cells under the sympathetic modulation in ITP remain unknown. Methods: Whole-tissue immunolabeling and 3D imaging of the human spleen were performed to compare the sympathetic distribution between ITP with splenectomy and non-ITP with traumatic splenectomy. RNA sequencing was used to detect the transcriptional changes and metabolomics and seahorse extracellular flux analyses were carried out to determine the metabolic reprogramming in splenic macrophages of ITP mice. The expression of cell surface markers of macrophages and T cells and cytokines was assessed by flow cytometry, western blot, and enzyme-linked immunosorbent assay. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA), a β2-AR agonist terbutaline, and a β2-AR antagonist ICI 118,551 were used to detect the sympathetic modulation. Genetic lineage tracing was used to compare serum norepinephrine (NE) and its origin in the spleen of WT mice with or without chemical sympathectomy. Results: A panicle-shaped sympathetic neural architecture was revealed in the spleen of both ITP and non-ITP patients. The distribution of sympathetic nerves in the spleen and the level of serum NE were both significantly decreased in ITP patients. Immunofluorescence staining revealed an anatomical colocalization between sympathetic nerves, macrophages, and T cells in the spleen, suggesting potential sympathetic modulation of macrophages and a potential interaction between splenic macrophages and T cells. RNA-sequencing data of splenic macrophages in ITP mice compared with wild type (WT) mice revealed higher expression of M1-specific genes, including IL1b, Tnf and IL6, and lower expression of M2-specific genes, including IL10 and Arg1, indicating an M1 polarization tendency. In splenic macrophages isolated from ITP mice, we observed an enrichment of glycolysis pathway genes compared to WT mice, including Hk2, Pkm2and Ldha. An increase in the extracellular acidification rate and a decrease in the oxygen consumption rate were also found in splenic macrophages of ITP mice, indicating a switch to glycolysis. To investigate the interaction between splenic macrophages and T cells under sympathetic modulation in ITP, we measured the expression of cytokines that might have an influence on macrophage polarization and T cell differentiation and observed upregulation of interleukin (IL)-12, IL-18 and interferon (IFN)-γ. We also used macrophages from ITP mice and WT mice as antigen-presenting cells for naïve CD4 + T cells, which were interrogated for IFN-γ production following stimulation with OVA 323-339. We observed increased IFN-γ production and upregulation of IL-12 and IL-18 in response to macrophages from ITP mice, and we also observed diminished production of IL-12, IL-18 and IFN-γ when pretreated with aIL-12 mAb and aIL-18 mAb. Moreover, chemical sympathectomy with 6-OHDA was carried out in WT mice and significantly decreased serum NE and platelet counts at D7 and D14 were observed. Increased expression of M1-specific markers and upregulation of IL-12, IL-18 and IFN-γ were also determined. The β2-AR agonist terbutaline was shown to decrease the expression of proinflammatory factors and inhibit M1 polarization, and its effects were reversed by the β2-AR antagonist ICI 118,551. Conclusions: Splenic sympathetic denervation-mediated proinflammatory M1 polarization, metabolic alterations, and proinflammatory interactions between macrophages and T cells were involved in ITP pathogenesis. The β2-AR agonist terbutaline was demonstrated to restore the homeostasis of splenic macrophages, indicating a novel potential ITP treatment strategy.