Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

[Setting and optimization of control group in acupuncture animal experiment based on research elements].

Acupuncture animal experiment is the main form of acupuncture mechanism research, in which, the setting of control group is crucial to the scientificity and reliability of research conclusion, and the research elements are the fundamental. Focusing on the research elements involved in acupuncture animal experiment, this study summarized the current situation and characteristics of the control groups related to acupoint selection, intervention and pathological mechanism in acupuncture animal experiment, and put forward the questions and suggestions so that the references of setting control group can be provided for acupuncture animal experiment in future.

[Research progress and reflection on mechanisms of acupuncture against primary dysmenorrhea].

Research articles on the mechanisms of acupuncture in the treatment of dysmenorrhea model in rats were retrieved from PubMed and China National Knowledge Infrastructure (CNKI). As revealed by the analysis, the underlying mechanisms were mainly related to the regulation of endocrine system and neurotransmitters, the modulation of immunoinflammatory responses, the improvement of uterine microcirculation, and reduction of oxidative stress. In the future, research should be carried out to explore the mechanism of acupuncture in relieving dysmenorrhea via acupoints and the specific mechanism of classical acupoints, so as to enrich the multi-pathway mechanisms of acupuncture in treating dysmenorrhea and provide more scientific basis for optimizing clinical modalities for primary dysmenorrhea treatment by acupuncture.

[Practical value and thought on "co-regulation of body and mind" in treatment of post-stroke spasticity with acupuncture].

This paper reviews the application of "co-regulation of body and mind" of acupuncture for post-stroke spasticity. It is found that acupoints on the head and the back of the governor vessel, as well as Jiaji (Ex-B 2) points are mainly used for regulating the mind, and the local sites of spastic muscles and the points on the antagonistic muscles are for regulating the body specially. It is believed that regulating the mind should be integrated with regulating the body, while, the acupoint selection be associated with needling methods so as to fully achieve the "co-regulation of body and mind" and enhance the practical value of acupuncture for post-stroke spasticity. It is proposed that the classical anti-spastic needling techniques, such as huici (relaxing needling) and guanci (joint needling), should be more considered.

Acupuncture improves the structure of spastic muscle and decreases spasticity by enhancing GABA, KCC2, and GABAAγ2 in the brainstem in rats after ischemic stroke.

BACKGROUND: Increasing data show that structural changes of spastic muscle and hyperexcitability of reticulospinal tract (RST) are involved in the pathogenesis of spasticity after stroke (SAS). Our previous study has indicated that the anti-spastic effect of acupuncture, especially waggle needling (WN, a multiple directional needling method with joint movement), on SAS rats was related to the KCC2-GABAA pathway in cerebral cortex. Furthermore, as a peripheral stimulation to treat upper motor neuron injury-related spasticity, acupuncture's effect on peripheral spastic muscles and inhibitory neurotransmitters in the brainstem, the origin of the RST, should be further clarified. This study aimed to examine the effect of acupuncture on the structure of spastic muscle and on the KCC2-GABAA pathway in the brainstem of SAS rats. METHODS: Middle cerebral artery occlusion (MCAO) or a sham operation were conducted in SD rats to establish SAS and control models. Behavioral assays, muscle myosin ATPase staining, and molecular biology technologies were used to compare different groups. RESULTS: In SAS models, hindlimb motor ability was decreased, neurologic deficits and spasticity were induced, the proportion of type I muscle fibers in spastic muscle was increased, and the expressions of γ-aminobutyric acid (GABA), KCC2, and the GABAAγ2 subunit of the pentameric GABAA receptor in the brainstem were decreased. Acupuncture including WN and perpendicular needling (PN) reversed these effects of MCAO. Furthermore, the therapeutic effect of WN was better than that of PN. CONCLUSIONS: Acupuncture after MCAO improves the structure of spastic muscle and decreases spasticity probably at least partly by enhancing GABA, KCC2, and GABAAγ2 in the brainstem in SAS rats.

[Study on the central mechanism of acupuncture for post-stroke spasticity based on the Na+/K+-ATPase-EAATs-Glu pathway].

OBJECTIVE: To observe the effect of acupuncture at "Yanglingquan" (GB34) and "Baihui" (GV20) on Na+/K+-ATPase, excitatory amino acid transporters (EAATs) and glutamate (Glu) in hippocampus of post-stroke spasticity rats, so as to explore the central mechanism in anti-spasticity. METHODS: In a total of 48 healthy SD rats, 12 rats were randomly selected to be included into sham operation group, and the remaining rats were used to make a middle cerebral artery occlusion (MCAO) model using a suture method. On the 3rd day after modeling, MCAO limb spasticity rats were screened by neurological deficit symptoms and muscle tension scores, and randomly divided into the model, GB34 (Hui-puncture at GB34) and GB34+GV20 (Hui-puncture at GB34 and horizontal insertion at GV20) groups (n=12 rats in each group), and the treatment was lasted for 7 conse-cutive days. The neurological symptoms and muscle tension score were observed with the Zea Longa score and modified Ashworth scale (MAS). The levels of Glu, EAAT1 (GLAST) and EAAT2 (GLT-1) in the ischemic area of cerebral hippocampus were detected by ELISA, the expression of Na+/K+-ATPase α1 (ATP1α1) was detected by Western blot, the expression of ATP1α1 mRNA was detected by real-time PCR, and the expression of GLAST, GLT-1 and ATP1α1 was detected by immunofluorescence. RESULTS: After modeling, Zea Longa score and MAS score were increased (P<0.01), the level of Glu in the ischemic area of cerebral hippocampus was increased (P<0.01), while the expression levels of GLAST, GLT-1, ATP1α1 protein and mRNA were all decreased (P<0.01) in the model group relevant to the sham operation group. After 7 days' treatment, all the increased and decreased levels of the indexes mentioned above were reversed in the two acupuncture groups relevant to the model group (P<0.01, P<0.05), and the effects of acupuncture at GB34+GV20 were obviously superior to that of acupuncture at GB34 (P<0.05, P<0.01). CONCLUSION: Acupuncture can alleviate post-stroke spasticity effectively, which may be related to its effect in up-regulating the expressions of Na+/K+-ATPase and EAATs in hippocampus. The anti-spastic effect of acupuncture at GB34+GV20 is superior to GB34 alone.

[Effect of different acupuncture and moxibustion methods on uterine contraction and microcirculation in cold congealing dysmenorrhea rats].

OBJECTIVE: To observe and compare the effects of different acupuncture and moxibustionmethods at "San-yinjiao" (SP6) on uterine contraction and microcirculation in cold congealing dysmenorrhea rats, so as to explore its mechanism underlying treatment of dysmenorrhea. METHODS: A total of 140 female SD rats were randomly divided into normal control, mo-del, perpendicular needling, transverse needling and moxibustion groups, with 28 rats in each group. The cold congealing dysme-norrhea rat model was prepared by exposure in a freezer (25 ℃) for 4 h, once daily for 5 days, and subcutaneous injection of estradiol benzoate (once daily for 10 days) and intra-abdominal injection of oxytocin (once). For rats in three intervention groups, acupuncture needles were inserted into bilateral SP6 perpendicularly or transversely to a depth of 4~5 mm and retained for 20 min, or moxibustion was applied to SP6 for 20 min. The uterine contraction degree and the uterine microcirculation were recorded. The expression levels of transient receptor potential vanilloid 1 (TRPV1) and heat shock protein 70 (HSP70) in local tissues of SP6 area were detected by immunohistochemistry. The expression levels of µopioid receptor and endothelin 1 (ET1) mRNA in the uterus were assessed by quantitative real time-PCR. RESULTS: After modeling and compared with the normal control group, the number and peak-to-peak values of uterine contraction waves, and uterine motility were significantly increased (P<0.01,P<0.05), while the speed of blood flow in the microvessels was slowed down (P<0.01), diameters of the uterine microvessels and capillaries (cap) shrank obviously (P<0.01) in the model group. After the intervention, all indexes of uterine contraction and microcirculation were improved in three intervention groups (P<0.01, P<0.05), while transverse needling and moxibustion showed better effects compared to perpendicular needling (P<0.05, P<0.01). The expression of TRPV1 and HSP70 in SP 6 area had no significant changes (P>0.05), while the uterine µopioid receptor mRNA expression decreased (P<0.01), and ET1 mRNA expression increased (P<0.01) in the model group relevant to the normal control group. Following the intervention, the expression levels of TRPV1 and HSP70 in SP6 area were increased (P<0.05, P<0.01), and expression levels of uterine µopioid receptor mRNA increased (P<0.05, P<0.01) and uterine ET1 mRNA decreased (P<0.05, P<0.01) in the three intervention groups. The effect of moxibustion was considerably better than those of two acupuncture groups in up-regulating TRPV1 expression (P<0.05). Both transverse needling and moxibustion showed better effects of down-regulating uterine ET1 mRNA expression than perpendicular needling (P<0.01). CONCLUSION: Transverse needling and moxibustion at SP6 have a better effect of relieving ute-rine contraction and improving uterine microcirculation than perpendicular needling, which may be related to their effects in up-re-gulating the expression of TRPV1 and HSP70 in SP6 area, thereby modulating the mRNA expression of µ opioid receptor and ET1 in uterine tissue.

Acupuncture for Primary Dysmenorrhea: A Potential Mechanism from an Anti-Inflammatory Perspective.

The low adverse effects of acupuncture for primary dysmenorrhea (PD), known as one of the most commonly reported gynecological debilitating conditions affecting women's overall health, have been thus far confirmed. Moreover, it has been increasingly recognized that inflammation is involved in such menstrual cramps, and recent studies have further shown that the anti-inflammatory effects of acupuncture are helpful in its control. This review portrays the role of inflammation in PD pathophysiology, provides evidence from clinical and animal studies on acupuncture for inflammation-induced visceral pain, and reflects on acupuncture-related therapies for dysmenorrhea with regard to their anti-inflammatory characteristics. Further research accordingly needs to be carried out to clarify the effects of acupuncture on proinflammatory factors in PD, particularly chemokines and leukocytes. Future studies on this condition from an anti-inflammatory perspective should be also performed in line with the notion of emphasizing stimulation modes to optimize the clinical modalities of acupuncture. Additionally, the effects and mechanism of more convenient self-healing approaches such as TENS/TEAS for PD should be investigated.

[7-hydroxy sulfonation of liquiritigenin by recombinant SULT1A3 enzyme and HEK-SULT1A3 cells].

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.

[Effect of Qishen Yiqi droplet on adenylate contents in myocardium of cor pulmonale rats].

Cor pulmonale rat models were induced by a single intraperitoneal injection of monocrotaline(MCT), and the sham group received a single intraperitioneal injection of normal saline. After the model rats received intragastric administration of Qishen Yiqi droplet(QS) for 6 weeks, the contents of adenylate(ATP, ADP and AMP) in right myocardial tissues were measured by HPLC, and then the metabolism changes in myocardium of cor pulmonale rats with QS were investigated. The results showed that ATP, ADP, and AMP were well separated, with a good linearity within a certain range of concentration; and the recovery rates were within the range of 90%-108%. As compared with model group, the level of ATP was significantly elevated in high-dose treatment group; ADP contents showed an increasing trend and AMP contents showed a decreasing trend, indicating that QS could significantly improve energy metabolism system in myocardium. By using the HPLC, a qualitative and quantitative analysis method was given for the determination of ATP, ADP and AMP contents in myocardium, providing a method for energy metabolism measurement in biological samples.

Fast Separation and Sensitive Quantitation of Polymethoxylated Flavonoids in the Peels of Citrus Using UPLC-Q-TOF-MS.

A rapid, sensitive, and efficient ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method has been developed to analyze polymethoxylated flavonoids (PMFs) in 14 Citrus peels, including 7 Citrus reticulata (C. reticulata) and 7 Citrus sinensis (C. sinensis). In this study, fast separation can be achieved within 12 min and 42 PMFs have been identified including 33 flavones and 9 flavanones. Most C. reticulata were shown to contain more than 20 PMFs, except Guangxihongpisuanju (GX) containing only 12 PMFs, while most C. sinensis contained fewer than 20 PMFs, except Edangan (EG) containing as many as 32 PMFs. To our knowledge, there are few reports about the quantitation of PMFs using the MS response. Here, a MS quantitative method was established and systematically validated in linearity, precision, and recovery. The linearity was from 1.25 ng/mL to 1.0 µg/mL with the limit of detection (LOD) as low as 75 pg/mL and the limit of quantitation (LOQ) as low as 0.25 ng/mL. Up to 13 PMFs, more types than ever before, were undoubtedly identified and quantitated according to the PMF standards. The results showed that the contents of PMFs in the C. reticulata were generally higher than those in the C. sinensis. This study is systematic for analyzing PMFs and is of great significance because it can provide guidance on utilization of both PMFs and citrus germplasm resources in the future.

Lateralisation of cerebral response to active acupuncture in patients with unilateral ischaemic stroke: an fMRI study.

OBJECTIVE: Acupuncture is beneficial in treating stroke neuropsychiatric symptoms. The present study aimed to identify functional brain response to active acupuncture in patients with unilateral ischaemic stroke using functional MRI (fMRI). METHODS: A total of 10 patients aged 47-65 years with left hemispheric ischaemic stroke received single-session manual acupuncture at the TE5 point of the affected (right) forearm. A 6-min tactile control procedure in which an acupuncture needle tip was alternately touched and removed from the skin at the acupuncture point for 30 s each was performed first, followed by active acupuncture in a blocking paradigm consisting of six 30-s twist blocks of rotation interspersed between six 30-s blocks of rest. A whole brain scan was simultaneously conducted on a 3.0-T imager. Activated and deactivated brain regions during tactile stimulation and active acupuncture relative to rest were obtained via group analysis. RESULTS: Compared to tactile stimulation, needling with twist manipulation modulated many more widespread brain areas. All the brain areas activated and deactivated by active acupuncture relative to tactile stimulation were distributed in the primary sensorimotor and medial frontal cortex of the unaffected, but not the affected hemisphere. CONCLUSIONS: Active acupuncture results in lateralisation of functional cerebral response to the contralateral unaffected hemisphere in patients with unilateral stroke. This lateralisation may represent an effect of acupuncture in enhancing a compensatory process by redistributing functions into the intact cortex, particularly in the unaffected hemisphere.