OBJECTIVE: To observe the effects of acupuncture at \"antihypertensive acupoint prescription\" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension.
METHODS: Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the \"antihypertensive acupoint prescription\" (bilateral \"Renying\" [ST 9], \"Quchi\" [LI 11], \"Zusanli\" [ST 36], \"Taichong\" [LR 3] and \"Neiguan\" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA).
RESULTS: Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05).
CONCLUSIONS: Acupuncture at \"antihypertensive acupoint prescription\" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.
目的：观察针刺“降压方”对自发性高血压大鼠（SHR）内皮活性因子及相关自主神经递质的影响，探讨针刺降压的血管调节和中枢调控机制。方法：将30只SPF级雄性SHR随机分为模型组（15只）、针刺组（15只），另以15只京都种Wistar大鼠（WKR）为空白对照组（正常组）。针刺组予“降压方”（双侧“人迎”“曲池”“足三里”“太冲”“内关”）针刺，留针30 min，每日1次，共干预28 d。每周采用激惹评分动态评价大鼠交感激惹表征；通过全自动无创血压测量系统检测大鼠尾动脉血压；ELISA法检测血清降钙素基因相关肽（CGRP）、一氧化氮（NO）、内皮素-1（ET-1）、神经肽Y（NPY）含量；DAB显色原位杂交（CISH）检测颈内动脉、弓状核内皮型一氧化氮合酶（eNOS）及室旁核后部、延髓腹外侧CGRP mRNA表达；液相色谱及质谱联用检测室旁核前部肾上腺素（E）、去甲肾上腺素（NE）含量。结果：与正常组比较，模型组大鼠观察期间各时间点激惹评分及收缩压、舒张压升高（P<0.05）；与模型组比较，针刺组大鼠干预第3、4周后激惹评分及干预第2、3、4周后收缩压、舒张压降低（P<0.05）。与正常组比较，模型组大鼠血清CGRP、NO含量降低（P<0.05），血清ET-1、NPY含量及室旁核前部E、NE含量升高（P<0.05）；与模型组比较，针刺组大鼠血清CGRP、NO含量升高（P<0.05），血清ET-1、NPY含量及室旁核前部E、NE含量降低（P<0.05）。模型组大鼠颈内动脉中膜增厚且有重构表现，弓状核神经元体积较小；针刺组大鼠颈内动脉各层排布尚可，弓状核小细胞神经元适中。各组大鼠eNOS mRNA在颈内动脉主要表达于各层中平滑肌细胞，而在弓状核主要表达于小细胞神经元。模型组大鼠室旁核后部神经分泌大细胞及小细胞分布较为稀疏，针刺组大鼠两类细胞排布尚可；模型组、针刺组大鼠延髓腹外侧区胶质细胞种类相对较少。各组大鼠CGRP mRNA在室旁核后部主要表达于神经分泌小细胞，而在延髓腹外侧主要表达于胶质细胞核及细胞质。与正常组比较，模型组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达降低（P<0.05）；与模型组比较，针刺组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达增加（P<0.05）。结论：针刺“降压方”可上调血管舒张因子水平，下调血管收缩因子水平，同时增强血管舒缩因子靶向血管及调控中枢的响应，其机制可能与调节SHR室旁核交感肾上腺素能自主神经递质有关。.

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.

BACKGROUND: Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB.
METHODS: In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured.
RESULTS: In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, β=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04).
CONCLUSIONS: This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease.

Repeated bouts of high-intensity interval training (HIIT) induce an improvement in metabolism via plasticity of melanocortin circuits and attenuated hypothalamic inflammation. HIF-1α, which plays a vital role in hypothalamus-mediated regulation of peripheral metabolism, is enhanced in the hypothalamus by HIIT. This study aimed to investigate the effects of HIIT on hypothalamic HIF-1α expression and peripheral metabolism in obese mice and the underlying molecular mechanisms. By using a high-fat diet (HFD)-induced obesity mouse model, we determined the effect of HIIT on energy balance and the expression of the hypothalamic appetite-regulating neuropeptides, POMC and NPY. Moreover, hypothalamic HIF-1α signaling and its downstream glycolytic enzymes were explored after HIIT intervention. The state of microglia and microglial NF-κB signaling in the hypothalamus were also examined in vivo. In vitro by using an adenovirus carrying shRNA-HIF1β, we explored the impact of HIF-1 signaling on glycolysis and NF-κB inflammatory signaling in BV2 cells. Food intake was suppressed and whole-body metabolism was improved in exercised DIO mice, accompanied by changes in the expression of POMC and NPY. Moreover, total and microglial HIF-1α signaling were obviously attenuated in the hypothalamus, consistent with the decreased levels of glycolytic enzymes. Both HFD-induced microglial activation and hypothalamic NF-κB signaling were significantly suppressed following HIIT in vivo. In BV2 cells, after HIF-1 complex knockdown, glycolysis and NF-κB inflammatory signaling were significantly attenuated. The data indicate that HIIT improves peripheral metabolism probably via attenuated HFD-induced microglial activation and microglial NF-κB signaling in the hypothalamus, which could be mediated by suppressed microglial HIF-1α signaling.

OBJECTIVE: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV).
METHODS: A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups.
RESULTS: After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05).
CONCLUSIONS: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.
目的：观察项七针联合压灸治疗颈性眩晕（CV）的临床疗效。方法：将70例CV患者随机分为观察组和对照组，每组35例。观察组采用项七针联合压灸治疗，每日1次，每周6次，连续治疗2周。对照组予口服盐酸倍他司汀片（2周）和醋氯芬酸分散片（3 d）。分别于治疗前后观察两组患者颈性眩晕症状与功能评估量表（ESCV）评分，检测血浆神经肽Y（NPY）、内皮素-1（ET-1）、降钙素基因相关肽（CGRP）含量及血液流变学、血流动力学指标，并于治疗后评定两组临床疗效。结果：治疗后，两组患者ESCV眩晕、日常生活及工作能力、心理及社会适应能力、头痛评分及总分较治疗前升高（P<0.01，P<0.05），观察组患者颈肩痛评分较治疗前升高（P<0.01）；观察组患者ESCV各项评分及总分均高于对照组（P<0.01，P<0.05）。治疗后，两组患者血浆NPY和ET-1含量较治疗前降低（P<0.01），血浆CGRP含量较治疗前升高(P<0.01，P<0.05)；观察组患者血浆NPY、ET-1含量低于对照组（P<0.01），血浆CGRP含量高于对照组（P<0.01）。治疗后，两组患者全血高切黏度、血浆黏度、全血低切黏度均较治疗前降低（P<0.01，P<0.05），基底动脉（BA）、左侧椎动脉（LVA）、右侧椎动脉（RVA）平均血流速度均较治疗前升高（P<0.05）；观察组患者全血高切黏度、血浆黏度及全血低切黏度均低于对照组（P<0.01），BA、LVA、RVA平均血流速度均高于对照组（P<0.05）。观察组总有效率为91.4%（32/35），高于对照组的71.4%（25/35，P<0.05）。结论：项七针联合压灸可有效减轻CV患者临床症状，改善血液流变学及血流动力学。.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]-NPY and [Leu31, Pro34]-NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

OBJECTIVE: To investigate the effects of the combined application of percutaneous vertebroplasty and zoledronic acid on bone mineral density (BMD), bone metabolism, neuropeptide Y (NPY) and prostaglandin E2 (PGE2) in elderly patients with osteoporotic lumbar vertebral compression fracture (OVCF).
METHODS: The medical records of 118 elderly patients with OVCF who received treatment at our hospital from March 2018 to March 2020 were collected and analyzed retrospectively. Vertebral body height, spinal function, pain degree, and lumbar BMD were compared between the two groups upon admission and three years after the operation. Additionally, the levels of bone-specific alkaline phosphatase (BALP), 25-hydroxyvitamin D (25-(OH)D), beta collagen degradation fragments (β-CTx), neuropeptide Y (NPY), and prostaglandin E2 (PGE2) in the two groups were measured at admission and three years after the operation. Furthermore, complications in the two groups within three years after the operation were documented.
RESULTS: After three years post-operation, the combination group showed a significantly greater improvement in vertebral body height compared to the control group (P<0.05). Moreover, the combination group exhibited a significantly lower Oswestry Disability Index (ODI) score compared to the control group (P<0.05).
CONCLUSIONS: In elderly patients with OVCF, the combined use of zoledronic acid and percutaneous vertebroplasty is effective in improving lumbar function, BMD, and bone metabolism indices, while reducing pain and the levels of NPY and PGE2.

UNASSIGNED: Postoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting.
UNASSIGNED: From January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring.
UNASSIGNED: Among 120 cases with no previously diagnosed AF, 33 (27.5 %) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P = 0.014). Multivariable logistic regression analysis revealed age (OR = 1.135, 95%CI 1.054-1.223; P = 0.001), left atrial size (OR = 1.136, 95%CI 1.004-1.285; P = 0.043), and NPY levels in peripheral blood (OR = 1.055, 95%CI 1.002-1.111; p = 0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r = 0.2774, P = 0.0022) and low-frequency (LF) (r = 0.2095, P = 0.0217) components of heart rate variability.
UNASSIGNED: In summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.