[Progress of mechanism research on the neurotransmitters in treatment of insomnia with acupuncture by regulating sleep architecture].

Low-quality sleep in patients with insomnia is closely related to sleep architecture imbalance and neurotransmitter impairment. Acupuncture may reduce the duration of light sleep and its proportion, increase the time of deep sleep and rapid- eye-movement sleep as well as their proportions so as to modulate the sleep architecture for insomnia. The paper summarized the related studies of acupuncture for improving sleep architecture through regulating serotonin, norephinephrine, dopamine, γ-aminobutyric acid, acetylcholine and orexin; and explored the effects of acupuncture on the neurotransmitters and their specific performance in regulating sleep architecture. It is anticipated that the review may provide the literature evidences of acupuncture for improving sleep quality in patients with insomnia, and the approaches to the mechanism research of acupuncture for regulating sleep architecture.

[Acupoint compatibility effect and mechanism of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia].

OBJECTIVE: To observe the acupoint compatibility effect of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia, and its mechanism in regulating hypothalamic-pituitary-adrenal (HPA) axis and suprachiasmatic nucleus-pineal gland-melatonin (SCN-PG-MT) system. METHODS: Ninety patients with insomnia were randomly divided into HT7, SP6 and HT7-SP6 (HT7 plus SP6) groups, with 30 cases in each group. Electroacupuncture (EA,5 Hz/25 Hz) was applied to HT7, SP6 or HT7-SP6 in each group for 30 min. The EA treatment was conducted once daily, 5 days a week for 2 weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were observed, separately. The contents of serum adrenocorticotrophic hormone (ACTH), cortisol (CS) and melatonin (MT) were detected by ELISA. RESULTS: Compared with before treatment, the sleep quality, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI in the three groups after treatment were decreased (P<0.05), the time to fall asleep score of PSQI and total score of ESS were decreased in the SP6 and HT7-SP6 groups (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep efficiency, daytime dysfunction scores, total score of PSQI and total score of ESS in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), the sleep quality, sleep efficiency and total score of PSQI in the SP6 group were lower than those in the HT7 group (P<0.05). Compared with before treatment, the serum ACTH and CS levels in the three groups were decreased (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were increased (P<0.05). After treatment, the ACTH and CS levels in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were higher than that in the HT7 group (P<0.05). CONCLUSION: The compatibility of HT7 and SP6 has a synergism effect on the improvement of night sleep quality and daytime fatigue and sleepiness of insomnia patients, the mechanism may be related with its function in down-regulating the serum ACTH and CS levels and increasing the serum MT content. SP6 has a better effect than HT7, and plays a major role in acupoint compatibility.

[Combined use of Shenmen (HT 7) and Sanyinjiao (SP 6) to improve the anxiety and depression in patients with insomnia: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at Shenmen (HT 7) and Sanyinjiao (SP 6) on anxiety and depression in patients with insomnia, and to explore the mechanism of its compatibility effect. METHODS: Ninety patients of insomnia were randomly divided into a combination group, a Shenmen group and a Sanyinjiao group, 30 cases in each group. In addition, 37 cases with anxiety (12 cases in the combination group, 13 cases in the Shenmen group and 12 cases in the Sanyinjiao group) and 42 cases with depression (14 cases in the combination group, 14 cases in the Shenmen group and 14 cases in the Sanyinjiao group) were identified. The patients in the combination group, Shenmen group and Sanyinjiao group were treated with EA (dilatational wave, frequency of 5 Hz/25 Hz) at Shenmen (HT 7)-Sanyinjiao (SP 6), Shenmen (HT 7) and Sanyinjiao (SP 6), respectively, 30 min each treatment, once a day. The consecutive 5 days of treatments were taken as a course of treatment, and 2 courses of treatment were given. The insomnia severity index (ISI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were evaluated before and after treatment, and the serum contents of dopamine (DA) and norepinephrine (NE) were measured. RESULTS: Compared before treatment, the ISI, SAS and SDS scores in the three groups were all decreased after treatment (P<0.05), and the ISI score in the combination group was lower than that in the Shenmen group (P<0.05). Among the patients with anxiety, compared before treatment, the ISI, SAS scores and serum contents of DA were all decreased after treatment in the three groups (P<0.05), and the serum contents of NE in the combination group and Shenmen group were decreased after treatment (P<0.05); the SAS score and serum contents of NE in the combination group and Shenmen group as well as the ISI score in the combination group were lower than those in the Sanyinjiao group (P<0.05). Among the patients with depression, compared before treatment, the ISI, SDS scores and serum contents of DA were all decreased after treatment in the three groups (P<0.05), and the serum contents of NE in the combination group and Shenmen group were decreased after treatment (P<0.05); the ISI, SDS scores and serum contents of NE in the combination group as well as SDS score in the Shenmen group were lower than those in the Sanyinjiao group (P<0.05). CONCLUSION: EA at Shenmen (HT 7) and Sanyinjiao (SP 6) has advantages over EA at Sanyinjiao (SP 6) on improving insomnia, anxiety and depression. Shenmen (HT 7) plays a major role in improving anxiety and depression. Shenmen (HT 7) and Sanyinjiao (SP 6) may play a compatibility effect of regulating consciousness and sleeping by reducing the level of serum NE.

Cornuside Alleviates Diabetes Mellitus-Induced Testicular Damage by Modulating the Gut Microbiota.

BACKGROUND: Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. METHODS: KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. RESULTS: Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. CONCLUSIONS: Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota.

Combination of the Herbs Radix Rehmanniae and Cornus Officinalis Mitigated Testicular Damage From Diabetes Mellitus by Enhancing Glycolysis via the AGEs/RAGE/HIF-1α Axis.

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as "nourishing Yin and tonifying kidney" herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of "kidney governing reproduction" in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

A Preclinical System Prototype for Focused Microwave Breast Hyperthermia Guided by Compressive Thermoacoustic Tomography.

OBJECTIVE: As a newly developed technique, focused microwave breast hyperthermia (FMBH) can provide accurate and cost-effective treatment of breast tumors with low side effect. A clinically feasible FMBH system requires a guidance technique to monitor the microwave power distribution in the breast. Compressive thermoacoustic tomography (CTT) is a suitable guidance approach for FMBH, which is more cost-effective than MRI. However, no experimental validation based on a realized FMBH-CTT system has been reported, which greatly hinders the further advancement of this novel approach. METHODS: We developed a preclinical system prototype for the FMBH-CTT technique, containing a microwave phased antenna array, a microwave source, an ultrasound transducer array and associated data acquisition module. RESULTS: Experimental results employing homogeneous and inhomogeneous breast-mimicking phantoms demonstrate that the CTT technique can offer reliable guidance for the entire process of the FMBH. In addition, small phase noises do not deteriorate the overall performance of the system prototype. CONCLUSION: The realized preclinical FMBH-CTT system prototype is capable for noninvasive, accurate and low-side-effect breast tumor treatment with effective guidance. SIGNIFICANCE: The experimentally validated FMBH-CTT system prototype provides a feasible paradigm for CTT guided FMBH, establishes a practical platform for future improvement of this technique, and paves the way for potential clinical translation.

Acupoint combination effect of Shenmen (HT 7) and Sanyinjiao (SP 6) in treating insomnia: study protocol for a randomized controlled trial.

BACKGROUND: Insomnia is a global disease with a high incidence and acupuncture therapy is a well appropriate method to treat insomnia. Shenmen (HT 7) and Sanyinjiao (SP 6) are the acupoints most commonly used to treat insomnia. Although they can obviously relieve the clinical symptoms of insomnia, it is unclear whether they must be used together, whether the combination of two acupoints may have a synergistic or antagonistic effect, and whether there is a primary or secondary relationship between the two points in the treatment of insomnia. Further studies are needed. Therefore, in this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia. METHODS/DESIGN: This will be a parallel group randomized controlled trial. The study will recruit 120 patients with insomnia randomly assigned to a control group, an electroacupuncture on HT 7 group, an electroacupuncture on SP 6 group, and an electroacupuncture on HT 7 and SP 6 group. The allocation ratio is 1:1:1:1, with 30 subjects in each group. Meanwhile, ten healthy subjects who meet the study criteria will be recruited as the healthy control group. Patients in the intervention groups will be given ten rounds of electroacupuncture stimulation on the corresponding acupoints for 2 weeks, five times per week, with 2 days of rest between the two treatment courses. Patients in the control group will also receive the same two courses of ten rounds of compensatory acupuncture therapy after a 2-week waiting period for treatment. The major outcome measures of this study include the Sleep Dysfunction Rating Scale, the Insomnia Severity Index, Epworth Sleepiness Scale, the Zung Self-Rating Anxiety Scale, and the Zung Self-Rating Depression Scale, combined with the Measure Your Medical Outcome Profile, to evaluate insomnia and the emotional state of patients with insomnia. The secondary outcome measures include sleep composition monitored by polysomnography and measurements of acetylcholine, serotonin, dopamine, norepinephrine, melatonin, gamma-aminobutyric acid, and metabolic biomarkers in serum. DISCUSSION: In this study, we are exploring the acupoint combination effect and biological mechanism of HT 7 and SP 6 in treating insomnia, which may provide evidence for the clinical application of acupuncture and acupoint selection in the treatment of insomnia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Chi-CTR-1800017483. Registered on 1 August 2018.

[Effect of electroacupuncture at "Shenmen"(HT7) and "Sanyinjiao"(SP6) on energy metabolism in paraventricular nucleus of hypothalamus of insomnia rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) at "Shenmen"(HT7) and "Sanyinjiao"(SP6)on energy metabolism in paraventricular nucleus (PVN) of hypothalamus in insomnia rats, so as to explore its mechanism underlying improvement of insomnia. METHODS: A total of 66 SD rats (half male and half female) were randomized into 3 groups：normal control, model and EA groups(n＝22 per group). The insomnia model was established by binding the rat for at least 4 h (step increase of 30 min per day), once daily for 15 days. EA (5 Hz /25 Hz, 0.5－1.0 mA) was applied to unilateral HT7 and SP6 for 15 min, once daily for 5 days. The rats' spontaneous activities during day and night were recorded by using the ClockLab Data Collection and Analysis System, and the duration of exhausted swimming was detected by using load-bearing endurance swimming test. The expression of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) of PVN tissue was assayed by Western blot, and the contents of acetyl coenzyme A (Ac-CoA) and Na＋-K＋adenosine triphosphatase (Na＋-K＋-ATPase) in the PVN tissue, and corticosterone (CORT) in plasma were assayed by ELISA. Changes of the ultrastructure of PVN cells were observed by transmission electron microscope. RESULTS: After modeling, the rats' daytime and nocturnal locomotor activities were significantly increased and decreased, respectively (P<0.05), and the duration of exhausted swimming was considerably shortened in the model group compared with that of the normal control group (P<0.05). The expression level of AMPK protein in the PVN was obviously up-regulated (P<0.05), and the contents of Ac-CoA and Na＋-K＋-ATPase in PVN and CORT in plasma were markedly decreased in the model control group relevant to the normal group (P<0.05). After EA intervention, the increased daytime locomotion and the decreased nocturnal activities, the shortened duration of exhausted swimming, the up-regulated expression of AMPK, and the decreased Ac-CoA, Na＋-K＋-ATPase and CORT contents were all reversed in the EA treated rats relevant to those of the insomnia rats (all P<0.05). Moreover, ultrastructural observation showed mitochondrial swelling and disappearance of partial ribosomes in the plasma of PVN cells in the model group, while in the EA group, only mild swelling of some mitochondria was found, being with basically normal nuclear membrane, mitochondria, rough endoplasmic reticulum, Golgi complex and ribosomes. CONCLUSION: EA at HT7 and SP6 has a positive effect in improving insomnia and insomnia-induced fatigue in insomnia rats, which may be associated with its effects in restraining the expression of AMPK protein, and up-regulating the contents of Ac-CoA and Na＋-K＋-ATPase in PVN and CORT in plasma.

Blueprints for the rational design of therapeutic mutacin 1140 variants.

Lantibiotics represent a large untapped pipeline of attractive scaffolds for the development of novel antibiotics. Saturation mutagenesis was employed to substitute every amino acid of a lantibiotic called mutacin 1140 (MU1140), creating an unbiased expression library of 418 variants that was used to study the permissiveness to mutagenesis and the "drugability" of several compounds. Contrasting previous reports, the results from this study supported that not all residues involved in lanthionine bridge formation were critical for maintaining optimal activity. While substitutions in lanthionine bridges in Ring A, C, and D invariably lead to inactive variants, permissive substitutions in Abu8 and Ala11 (Ring B) were observed, albeit infrequently. Further, the data generated suggested that the unsaturated bond from Dha5 (Ser5) may not be critically involved in Lipid-II binding but still important for conferring optimal activity. This study identified additional permissive mutations of Ser5, including Ser5His, Ser5Met, Ser5Gln, and Ser5Leu. In contrast, no permissive substitutions were identified for Dhb14, which suggested that this residue may be critical for optimal activity. Novel blueprints are proposed for directing further development of MU1140 variants and other lantibiotics, which may enable the rational design, development, manufacture, and formulation of an entirely new class of anti-infectives.

Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex.

Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. Here, we show a major genetic effect on rhythmic methylation in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). More than 23,000 diurnally rhythmic CpGs are identified in wild-type cortex, with nearly all lost or phase-shifted in PWS. Circadian dysregulation of a second imprinted Snord cluster at the Temple/Kagami-Ogata syndrome locus is observed at the level of methylation, transcription, and chromatin, providing mechanistic evidence of cross-talk. Genes identified by diurnal epigenetic changes in PWS mice overlapped rhythmic and PWS-specific genes in human brain and are enriched for PWS-relevant phenotypes and pathways. These results support the proposed evolutionary relationship between imprinting and sleep, and suggest possible chronotherapy in the treatment of PWS and related disorders.

[Effects of electroacupuncture on anxiety and sympathetic-adrenal medulla system in rats with insomnia].

OBJECTIVE: To explore the action mechanism of electroacupuncture (EA) at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) on insomnia. METHODS: Thirty SD rats were randomly divided into a blank group, a model group and an EA group, 10 cases in each group. The insomnia model was made by immobilization method in the model group and EA group. After model establishment, rats in the blank group and model group were treated with fixation and no treatment was given. Rats in the EA group were treated with EA at "Shenmen" (HT 7) and "San-yinjiao" (SP 6) for 15 min, once a day for 4 days. After treatment, the level of daytime and nighttime activity, open-arm entry percentage and open-arm time percentage of elevated plus-maze test were measured; the content of noradrenaline (NE), dopamine (DA) and epinephrine (EPI) in plasma and NE, DA in thalamus and brainstem were detected by using euzymelinked immunosorbent assay method. RESULTS: Compared with the blank group, the daytime activity was increased and nighttime activity was reduced in the model group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both reduced in the model group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were increased in the model group (all P<0. 05). Compared with the model group, the daytime activity was reduced and nighttime activity was increased in the EA group (both P<0. 05); the open-arm entry percentage and open-arm time percentage of elevated plus-maze test were both increased in the EA group (both P<0. 05); the contents of NE, DA, EPI in the plasma and NE, DA in thalamus and brainstem were reduced in the EA group (all P< 0. 05). CONCLUSION: Electroacupuncture at "Shenmen" (HT 7) and "Sanyinjiao" (SP 6) can restrain the over-activity of the sympathetic-adrenal medullary system to treat the insomnia.

Acupuncture and stress / 中国针灸

The relationship between acupuncture and stress is discussed from three aspects, including is it possible for acupuncture stimulation to be a stressor, whether acupuncture will start stress reaction, and whether acupuncture effects contain some stress factors. It is believed that correct acupuncture manipulation will not cause stress response, however, under some circumstances, such as inaccurate manipulation, improper treatment or patients who are very nervous but do not receive effective intervention, acupuncture is likely to cause stress response. Acupuncture-induced stress response is totally different from acupuncture anti-stress. The possible stress factors in acupuncture effect are explored, which can provide a new angle for the research on action mechanism of acupuncture. From the view of stress to review acupuncture treatment, there are three enlightenments: emphasizing on communication between doctors and patients, avoiding over-pursuit of deqi and focusing on analysis of the body constitution.

[Discussion on the constructing principle of syndrome differentiation system according to meridian and collateral theories].

According to the meridian and collateral theories in the Internal Classic, the authors proposed that the construction of the syndrome differentiation system with science characteristics of acupuncture and moxibustion should follow the principle of systemic structure and physiological function. The establishment of the whole frame structure of syndrome differentiation system according to meridian and collateral theories should base on the principle of systemic structure and the establishment of symptom of each syndrome should base on the principle of physiological function.

[Effect of electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) on the event-related potentials of chronic fatigue syndrome].

OBJECTIVE: To observe the effective mechanism of electroacupuncture for chronic fatigue syndrome (CFS). METHODS: The dynamic detection of chronobiology was used to test the event-related potentials in 20 healthy subjects and 20 CFS patients. P3a and P3b latencies at 4 equidistant time points (8:00, 14:00, 20:00, 2:00) within 24 hours were collected and analyzed. RESULTS: (1) Latency of P3a in CFS group was obviously prolonged at 14:00 compared to health group with statistical significance (P < 0.05), latency of P3b was decreased at 14:00 after electroacupuncture treatment with statistical significance compared to that of pre-treatment (P < 0.01). (2) There were obviously circadian rhythm in latency of P3a and P3b in health group (P < 0.05), which were not seen in CFS group (P > 0.05); the circadian rhythm latency of P3b restored after treatment (P < 0.05). (3) The latency acrophase of P3a and P3b pre-treatment obviously shifted backward compared to that of healthy subjects (P < 0.05), shifted forward after electroacupuncture treatment (P < 0.05). CONCLUSION: The event-related potential circadian rhythms are lost in CFS patients. Electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) can regulate the circadian rhythm of P3a and P3b latency and improve the cognition of the patients in daytime.

High glycolytic flux improves pyruvate production by a metabolically engineered Escherichia coli strain.

We report pyruvate formation in Escherichia coli strain ALS929 containing mutations in the aceEF, pfl, poxB, pps, and ldhA genes which encode, respectively, the pyruvate dehydrogenase complex, pyruvate formate lyase, pyruvate oxidase, phosphoenolpyruvate synthase, and lactate dehydrogenase. The glycolytic rate and pyruvate productivity were compared using glucose-, acetate-, nitrogen-, or phosphorus-limited chemostats at a growth rate of 0.15 h(-1). Of these four nutrient limitation conditions, growth under acetate limitation resulted in the highest glycolytic flux (1.60 g/g . h), pyruvate formation rate (1.11 g/g h), and pyruvate yield (0.70 g/g). Additional mutations in atpFH and arcA (strain ALS1059) further elevated the steady-state glycolytic flux to 2.38 g/g h in an acetate-limited chemostat, with heterologous NADH oxidase expression causing only modest additional improvement. A fed-batch process with strain ALS1059 using defined medium with 5 mM betaine as osmoprotectant and an exponential feeding rate of 0.15 h(-1) achieved 90 g/liter pyruvate, with an overall productivity of 2.1 g/liter h and yield of 0.68 g/g.

[On effects of acupoints and drugs in acupoint-injection treatment].

Acupoint-injection therapy is a successful sample for clinical application of integrated Chinese and Western medicine, and has widely been applied clinically. In this method, effects of meridians, acupoints and drugs are organically combined, with obviously higher total therapeutic effect compared with routine acupuncture and moxibustion, intermuscular injection or intravenous injection. In this paper, the total therapeutic effects of acupoint-injection, high effectiveness of drugs and integrated action of acupoint and drug were discussed mainly and it is considered that the basic reason of acupoint-injection producing the high effect of drug is due to meridians and acupoints integrating some pharmacological actions of drugs.