Acupoint application for postherpetic neuralgia with qi stagnation and blood stasis and its effect on related inflammatory factors and 5-HT. / ç©´ä½è´´æ•·æ²»ç–—æ°”æ»žè¡€ç˜€åž‹å¸¦çŠ¶ç–±ç–¹åŽé—ç¥žç»ç—›åŠå¯¹ç›¸å ³ç‚Žæ€§å› å­ã€5-HT的影响.

OBJECTIVES: To observe the clinical efficacy of acupoint application in treating postherpetic neuralgia(PHN) with qi stagnation and blood stasis, and its effects on serum inflammatory factors and 5-hydroxytryptamine (5-HT) in patients. METHODS: A total of 136 PHN patients were randomly divided into an observation group (68 cases, 6 case dropped out) and a control group (68 cases, 5 cases dropped out). In the observation group, the combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder was used at bilateral Sanyinjiao (SP 6), Shenque (CV 8) and ashi points. Sanyinjiao (SP 6) was applied for 30 min per session, once every 7 days; and Shenque (CV 8) and ashi points were applied for 6-8 h per session, once every 1 day. In the control group, mecobalamin injection was administered at Jiaji (EX-B 2) corresponding to the neural segments governing the painful area, 1 mL per injection, once a day. Each treatment course consisted of 7 days, 4 treatment courses were required in both groups. The visual analog scale (VAS) score for pain, 36-item short form health survey (SF-36) score, traditional Chinese medicine syndrome score, and the serum levels of inflammatory factors (monocyte chemoattractant protein-1 [MCP-1], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α]) and 5-HT were compared in the patients of the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the VAS scores, traditional Chinese medicine syndrome scores, serum MCP-1, IL-6, TNF-α, and 5-HT levels were decreased compared with those before treatment in both groups (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). The SF-36 scores were increased compared with those before treatment in the two groups (P<0.05), and the result in the observation group was higher than that in the control group (P<0.05). The total effective rate of the observation group was 74.2% (46/62), which was higher than 52.4% (33/63, P<0.05) of the control group. CONCLUSIONS: The combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder has shown better efficacy in treating PHN with qi stagnation and blood stasis, which can significantly alleviate patients symptoms, improve their quality of life, and reduce serum levels of MCP-1, IL-6, TNF-α, and 5-HT.

Up-regulation of Proinflammatory Cytokines in Rostral Ventromedial Medulla Contributes to Chronic Postsurgical Pain by Promoting 5-HT Release / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Shugan Jianpi Yangxin Prescription Regulates Orexin-A and Its Receptors in Mouse Model of Insomnia / 中国实验方剂学杂志

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

TRAUMATIC EVENTS AND MENTAL DISEASES: THE ROLE OF CERTAIN NEUROTRANSMITTERS, METALLOENZYMES AND HORMONES

OBJECTIVE: Aim: To study the role of certain neurotransmitters (brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT)), metalloenzymes (matrix met-alloproteinase-9) (MMP-9) and hormones (ghrelin) in the pathogenesis of mental disorders associated with stress under the impact of traumatic events. PATIENTS AND METHODS: Materials and methods: We conducted a systematic search of major electronic medical databases published before October 1, 2022. Such keywords as (post-traumatic stress disorder OR PTSD), (Brain-derived neurotrophic factor OR BDNF), (matrix metalloproteinase-9 OR MMP-9), (serotonin OR 5-HT), ghrelin, melatonin identified relevant studies. All articles were reviewed, including original studies, systematic reviews and meta-analyses. CONCLUSION: Conclusions: Unfortunately, the imbalance of neurotransmitter systems of the brain remains not fully understood under such a condition at this stage of world science development. Their role remains unclear both during the immediate exposure to the stress factor and in the remote period. Therefore, under¬standing the mechanisms underlying the systemic consequences of PTSD is crucial for the development of prediction models and timely rational therapy.

Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.

BACKGROUND: Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain. OBJECTIVES: To detect the negative modulators of the 5-HT2A receptor as a cure for ADP. MATERIAL AND METHODS: The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events. RESULTS: Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05). CONCLUSION: Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the chinese Han population.

BACKGROUND: Lifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population. METHODS: In this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels. RESULTS: The results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49-0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35-0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36-0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52-0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22-0.90, p = 0.024) by haplotype analysis. CONCLUSION: HTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.

[Bloodletting at auricular dorsal vein combined with auricular point sticking for menstrual migraine of qi stagnation and blood stasis and its effect on serum levels of E2 and 5-HT].

OBJECTIVE: To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism. METHODS: A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment. RESULTS: Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05). CONCLUSION: Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.

APETx2 regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome mice through 5-HT signalling pathway.

OBJECTIVES: To investigate whether APETx2, a potent and selective inhibitor of ASIC3, regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome (PI-IBS) mice through the 5-HT signalling pathway. METHODS: The PI-IBS model was established by Trichinella spiralis infection of NIH mice. APETx2(120 µg/kg) was administrated to PI-IBS mice by intraperitoneal injection once a day, lasting for 7 days. The gastrointestinal function of mice was assessed by the time of the first dark stool and the number of pellets defecated within 2 h. The visceral sensitivity was tested via abdominal withdrawal reflex. The protein levels of 5-HT and CRF in colon tissues were detected by immunohistochemistry. The changes in serum 5-HT and colon CRF contents were detected by ELISA. The mRNA levels of colon 5-HT4R and CRF were detected by RT-qPCR. The protein levels of colon 5-HT4R and dorsal root ganglion (DRG) ASIC3 were detected by Western blotting. KEY FINDINGS: The results indicated that APETx2 could markedly improve gastrointestinal function and visceral sensitivity in mice. Moreover, APETx2 could reduce the expression level of ASIC3 protein in the DRG of PI-IBS mice. APETx2 could increase the expression levels of 5-HT in serum and colon, CRF and 5-HT4R in the colon, and 5-HT4R in brain tissue in PI-IBS mice. CONCLUSIONS: APETx2 can improve visceral sensitivity and intestinal motility in PI-IBS through 5-HT signalling pathway.

[Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats].

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Mechanism of Shaoyaotang in Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Shaoyaotang （SYT） in the treatment of ulcerative colitis （UC） based on network pharmacology and experimental verification. MethodThe core components， target genes， and main pathways of SYT were predicted based on network pharmacology， and UC-related components， target genes， and pathways were screened. Dextran sodium sulfate （DSS） was used to induce the UC model in mice， and the effect of SYT on UC mice was observed， followed by mechanism verification. ResultNetwork pharmacology indicated that 174 active components and corresponding 159 target genes of SYT were screened， and the related pathways were those mediated by 5-hydroxytryptamine （5-HT） degredation and 5-HT receptor 3. The results of animal experiments showed that compared with the model group， the SYT group showed increased body weight and colon length（P<0.01）， reduced disease activity index （DAI） score （P<0.01）， improved histopathological manifestations， reduced concentrations of 5-HT in the colonic tissues and serum （P<0.05， P<0.01）， and increased mRNA expression of monoamine oxidase A （MAOA）， monoamine oxidase B （MAOB）， sodium-dependent serotonin transporter （SLC6A4）， and 5-HT receptor 3A （5-HTR3A） related to 5-HT metabolism in the colon （P<0.01）. ConclusionSYT can alleviate the local inflammatory response of the intestinal tract in UC by regulating 5-HT degredation pathways.

Clinical Effect of Modified Jichuanjian on Senile Patients with Slow Transit Constipation of Spleen-kidney Yang Deficiency Syndrome and Effect on Brain-gut Peptide / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of modified Jichuanjian on senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome and the influence on brain-gut peptide. MethodA total of 150 senile patients with slow transit constipation were randomized into control group （75 cases） and observation group （75 cases） with the random number table method. The observation group was given modified Jichuanjian （oral， 1 dose/day， 4 weeks）， and the control group was treated with Biantong Capsules （oral， 3 capsules/time， twice/day， 4 weeks）. Data before and after treatment were recorded， including the score of major constipation symptoms， score of Patient Assessment of Constipation Quality of Life （PAC-QOL）， TCM syndrome score， spontaneous complete bowel movements （SCBM）， colonic transit test， serum 5-hydroxytryptamine （5-HT）， 5-HT 4 receptor （5-HT4R）， somatostatin （SS）， and vasoactive intestinal peptide （VIP）， and recurrence. ResultThe total effective rate of the observation group was 93.06% （67/72）， as compared with the 74.65% （53/71） in the control group （χ2=8.974 6， P<0.01）. After treatment， the scores of major constipation symptoms， scores of four dimensions of PAC-QOL， total score of PAC-QOL， and TCM syndrome score were lower than those before treatment in the two groups （P<0.01）， and lower in the observation group than in the control group （P<0.01）. The SCBM in the observation group were more than those in the control group at the 2nd， 3rd， 4th weeks after treatment （P<0.01）. The proportions of residual markers at 24， 48， 72 h after treatment were smaller than those before treatment in the two groups （P<0.01）， and smaller in the observation group than in the control group （P<0.01）. After treatment， the levels of serum 5-HT and 5-HT4R were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） than those before treatment in the two groups. In addition， the levels of serum 5-HT and 5-HT4R in the observation group were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） in the observation group than in the control group. The recurrence in the observation group was 29.85% （20/67） in comparison with the 58.49% （31/53） in the control group （χ2=9.932 4， P<0.01）. ConclusionModified Jichuanjian is effective for senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome， which can alleviate clinical symptoms， improve quality of life， regulate the level of serum brain-gut peptide， improve the colonic transit function， increase SCBM， and reduce the recurrence.

Clinical Effect of Tiaoxin Formula in Treatment of Patients with Coronary Heart Disease and Anxiety/Depression and Its Impact on Serum 5-HT， β-TG and MPO Levels / 中国实验方剂学杂志

ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine （5-HT）， β- thromboglobulin （β-TG） and myeloperoxidase （MPO）. MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group， 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally， the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment， the changes of clinical efficacy， Patient Health Questionnaire （PHQ-9）， Generalized Anxiety Disorder （GAD-7） scale， Seattle Angina Questionnaire （SAQ）， heart rate variability， and serum 5-HT， β-TG and MPO levels， and incidence of adverse reactions in the two groups were observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups， and thus the two groups were comparable. After treatment for 8 weeks， the total effective rate for traditional Chinese medicine （TCM） syndromes in the Tiaoxin Formula group was 87.88% （29/33） higher than 63.64% （21/33） in the Deanxit group （Z=-2.653， P<0.05）. Compared with those before treatment， the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment （P<0.05）， and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment （P<0.05）. Compared with the Deanxit group， the Tiaoxin Formula group had elevation in two dimension scores： Physical limitation and angina stability （P<0.05）. Compared with the conditions before treatment， the serum 5-HT level in the two groups were increased， while the β-TG and MPO levels were lowered （P<0.05）， and there was no distinct difference between two groups. In addition， the standard deviation of normal-to-normal intervals （SDNN） and standard deviation of average normal-to-normal intervals （SDANN） of the heart rate variability in the Tiaoxin formula group were elevated after treatment （P<0.05）， which were more significant than those of the Deanxit group （P<0.05）. During the treatment period， the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group （P<0.05）， and no adverse events were observed in the two groups. ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression， which improved the clinical symptoms， increased serum 5-HT levels， and decreased serum β-TG and MPO levels， and had few adverse reactions and high safety for patients， showing a high clinical value.

Effect of Magnolia officinalis Cortex Before and After Sweating on Distribution of Intestinal Flora and Levels of 5-HT and SP in IBS-C Rats / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome（IBS-C） rats before and after sweating. MethodIBS-C rat model was established by gavage of ice water， and rats were randomly divided into the blank group， model group， mosapride group（1 mg·kg-1）， M. officinalis cortex group（10 g·kg-1） and sweated M. officinalis cortex group（10 g·kg-1）. The changes of body weight， fecal number and fecal water content of rats were observed， 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats， the levels of 5-hydroxytryptamine（5-HT） and substance P（SP） in colonic tissues of rats were determined by enzyme-linked immunosorbent assay（ELISA）. ResultCompared with the model group， the fecal water content and fecal number of mosapride group， M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.05）. At the phylum level， the top four species of flora abundance were Firmicutes， Bacteroidetes， Spirochaetes and Proteobacteria. Compared with the blank group， the proportion of Firmicutes in the model group was significantly reduced（P<0.05）， while the proportion of Spirochaetes was significantly increased（P<0.05）. Compared with the model group， the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group， and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level， the top four species of flora abundance were Lactobacillaceae， S24_7， Ruminococcaceae， Bacteroidaceae， compared with the blank group， the proportion of Lactobacillaceae in the model group decreased significantly（P<0.05）， and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration（P<0.05）， and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level， the top four species of flora abundance were Lactobacillus， Unspecified_S24_7， Bacteroides and Treponema. Compared with the blank group， the proportion of Lactobacillus in the model group decreased significantly（P<0.05）， while the proportion of Treponema increased significantly（P<0.05）. Compared with the model group， ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group， indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group， the 5-HT content in mosapride group was significantly reduced（P<0.05）， the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.01）， and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group. ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.

Bloodletting at auricular dorsal vein combined with auricular point sticking for menstrual migraine of qi stagnation and blood stasis and its effect on serum levels of E2 and 5-HT / 中国针灸

OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Stress during puberty exerts sex-specific effects on depressive-like behavior and monoamine neurotransmitters in adolescence and adulthood.

Psychiatric disorders including major depression are twice as prevalent in women compared to men. This sex difference in prevalence only emerges after the onset of puberty, suggesting that puberty may be a sensitive period during which sex-associated vulnerability to stress-related depression might become established. Thus, this study investigated whether stress occurring specifically during the pubertal window of adolescence may be responsible for this sex difference in depression vulnerability. Male and female rats were exposed to a three-day stress protocol during puberty (postnatal days 35-37 in females, 45-47 in males) and underwent behavioral tests in adolescence or adulthood measuring anhedonia, anxiety-like behavior, locomotor activity and antidepressant-like behavior. Brainstem and striatum tissue were collected from a separate cohort of behavioral test-naïve rats in adolescence or adulthood to quantify the effect of pubertal stress on monoamine neurotransmitters. Pubertal stress increased immobility behavior in the forced swim test in both sexes in adolescence and adulthood. In adolescence, pubertal stress altered escape-oriented behaviors in a sex-specific manner: decreasing climbing in males but not females and decreasing swimming in females but not males. Pubertal stress decreased adolescent brainstem noradrenaline specifically in females and had opposing effects in adolescent males and females on brainstem serotonin turnover. Pubertal stress induced anhedonia in the saccharin preference test in adult males but not females, an effect paralleled by a male-specific decrease in striatal dopamine turnover. Pubertal stress did not significantly impact anxiety-like behavior or locomotor activity in any sex at either age. Taken together, these data suggest that although pubertal stress did not preferentially increase female vulnerability to depressive-like behaviors compared to males, stress during puberty exerts sex-specific effects on depressive-like behavior and anhedonia, possibly through discrete neurotransmitter systems.

High-resolution spatiotemporal analysis of single serotonergic axons in an in vitro system.

Vertebrate brains have a dual structure, composed of (i) axons that can be well-captured with graph-theoretical methods and (ii) axons that form a dense matrix in which neurons with precise connections operate. A core part of this matrix is formed by axons (fibers) that store and release 5-hydroxytryptamine (5-HT, serotonin), an ancient neurotransmitter that supports neuroplasticity and has profound implications for mental health. The self-organization of the serotonergic matrix is not well understood, despite recent advances in experimental and theoretical approaches. In particular, individual serotonergic axons produce highly stochastic trajectories, fundamental to the construction of regional fiber densities, but further advances in predictive computer simulations require more accurate experimental information. This study examined single serotonergic axons in culture systems (co-cultures and monolayers), by using a set of complementary high-resolution methods: confocal microscopy, holotomography (refractive index-based live imaging), and super-resolution (STED) microscopy. It shows that serotonergic axon walks in neural tissue may strongly reflect the stochastic geometry of this tissue and it also provides new insights into the morphology and branching properties of serotonergic axons. The proposed experimental platform can support next-generation analyses of the serotonergic matrix, including seamless integration with supercomputing approaches.

[Acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke depression: a randomized controlled trial].

OBJECTIVE: To observe the curative effect of Shugan Tiaoshen (soothing liver and regulating mind) acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke depression (PSD), and to explore its mechanism. METHODS: Ninety patients of PSD were randomly divided into an acupuncture+rTMS combination group (30 cases), a rTMS combination group (30 cases, 1 case dropped off) and a western medication group (30 cases, 1 case dropped off). The western medication group was treated with escitalopram oxalate tablets, 10 mg orally each time, once a day; on the basis of the treatment in the western medication group, the rTMS combination group was additionally given rTMS, and the frequency was 20 Hz, 20 min each time, once a day, 5 times a week; on the basis of the treatment in the rTMS combination group, the acupuncture+rTMS combination group was additionally treated with Shugan Tiaoshen acupuncture at Baihui (GV 20), Sishencong (EX-HN 1), Yintang (GV 24+), Shenting (GV 24), etc. for 40 min each time, once a day, weekly 5 times, and each group was treated for 4 weeks. Before and after treatment, the scores of Hamilton depression scale-17 (HAMD-17), Montreal cognitive assessment scale (MoCA), Pittsburgh sleep quality index (PSQI) were observed, and serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) were detected in each group. RESULTS: After treatment, the HAMD-17 scores in the three groups were lower than those before treatment (P<0.01), and the PSQI scores in the acupuncture+rTMS combination group and the rTMS combination group were lower than those before treatment (P<0.01); the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were lower than those in the western medication group (P<0.05), and the PSQI score in the acupuncture+rTMS combination group was lower than that in the rTMS combination group (P<0.05). After treatment, the MoCA scores and serum BDNF levels in the acupuncture+rTMS combination group and the rTMS combination group were higher than those before treatment (P<0.01), and the serum 5-HT levels in the three groups were higher than those before treatment (P<0.01); and the above indexes in the acupuncture+rTMS combination group and the rTMS combination group were higher than those in the western medication group (P<0.05), and which in the acupuncture+rTMS combination group were higher than those in the rTMS combination group (P<0.05). CONCLUSION: On the basis of western medication escitalopram oxalate, the addition of Shugan Tiaoshen acupuncture combined with rTMS therapy can effectively improve cognitive function and sleep quality in patients with PSD, and the effect is better than that of western medication alone or rTMS combined with western medication. Its mechanism of action may be related to the increase of peripheral serum 5-HT and BDNF levels.

Structural and metabolic activity differences in serotonergic cell groups in a rat model of individual differences of emotionality and stress reactivity.

Serotonin regulates a diverse set of functions, including emotional behavior, cognition, sociability, appetite, and sleep. Serotonin is also a key trophic factor that shapes neurodevelopmental processes. Genetic and environmental factors that drive individual differences in the serotonergic system have the capacity to impact brain structure and behavior, and likely contribute to pathophysiological processes involved in neuropsychiatric disorders. Using adult rats selectively bred for low novelty exploration (Low Responders, LR), we previously demonstrated pronounced increases in the levels of their anxiety- and depression- relevant behaviors as compared to the selectively bred High Novelty Responder (HR) rats. These behavioral differences were accompanied by alterations in the expression of genes that regulate serotonin synthesis in the brainstem, and its signaling in the forebrain. The present study extends these observations with a focus on the organization and the metabolism of brainstem serotonin cell groups that provide serotonergic innervation of the hippocampus and other limbic regions of male HR/LR rats. Using design-based stereology, we found the median raphe (MnR) in adult male LR rats contains increased number of serotonergic neurons as compared to the HRs. This is preceded by an increase in the metabolic activity of the caudal dorsal raphe (DRC) and the intrafascicular DR (DRI) during early postnatal development. These findings suggest that structural and functional differences in the raphe-limbic projections shape behavioral inhibition throughout the lifespan.