[Comparison of therapeutic efficacy of Wuling Capsules prepared with different methods for rats with syndrome of liver Qi stagnation, spleen deficiency, and blood stasis].

Wuling Capsules is one of the commonly used drugs for the clinical treatment of chronic hepatitis B with the syndrome of liver Qi stagnation, spleen deficiency, and blood stasis. However, the present preparation method of Wuling Capsules ignores some macromolecules like polysaccharides. In this study, the influences of different ethanol concentrations in the preparation process on the extraction rates of macro-and micro-molecules were investigated. Further, the therapeutic efficacy of Wuling Capsules was evaluated with the reserpine-induced rat model of liver Qi stagnation, spleen deficiency, and blood stasis. When 50% ethanol was used for the last time of extraction, the concentrations of polysaccharides, salvianolic acid B, and schisandrin in the extract, as well as the dry extract yield, increased significantly compared with those of the original preparation method. However, the fingerprints of micro-molecules showed little difference between the two methods, with a similarity of 0.862. The study then set the 50% ethanol extraction as the new preparation method. The pharmacodynamics evaluation showed that the Wuling Capsules prepared with the original and new methods both significantly alleviated the emotional depression and metabolic disturbance in model rats, demonstrating good performance in protecting the rats against gastric mucosal injuries, modulating intestinal function, and activating blood circulation. The mechanism of action may be related to the regulation of gastrointestinal hormone secretion, reduction of inflammation, and promotion of dopamine synthesis in cortex and hippocampus. At the same dose, the Wuling Capsules prepared with the original and new methods showed roughly the same overall therapeutic efficacy. However, the Wuling Capsules prepared with the new method had stronger effect in activating blood circulation and modulating inflammation, but weaker effects in regulating gastrin and dopamine. The present study provides basis data for optimizing the preparation process of Wuling Capsules and deciphering the mechanism of its therapeutic effect on liver Qi stagnation, spleen deficiency, and blood stasis.

[Clinical efficacy of acupuncture combined with modified Xiangfu Decoction in treatment of menopausal insomnia cause by liver Qi stagnation].

To evaluate the efficacy and safety of acupuncture combined with modified Xiangfu Decoction in the treatment of menopausal insomnia case by liver Qi stagnation. Totally 120 cases were randomly divided into the control group(60 cases) and the treatment group(60 cases). Estazolam and acupuncture combined with modified Xiangfu Decoction were given for 16 weeks. Before and after treatment, Epworth sleepiness scale(ESS), Pittsburgh sleep quality index(PSQI), Hamilton anxiety scale(HAMA) and traditional Chinese medicine(TCM) syndrome score were compared between the two groups. Polysomnography monitor was used to monitor sleep progress and sleep structure. Serum LH, FSH and E_2 were determined. The clinical efficacy and incidence of adverse reactions were observed. Four cases were lost during the study. The total effective rate in the treatment group was 91.5%, which was higher than that in the control group 75.4%(P<0.05). After treatment, the scores of clinical symptoms(ESS, PSQI, HAMA, TCM symptoms) in the treatment group were significantly reduced(P<0.05), and lower than that in the control group(P<0.05). TST, SE in the treatment group were increased(P<0.05), while AWT, SL, AT in the treatment group were decreased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). S_1 in the treatment group was decreased(P<0.05), whereas S_2, S_(3+4), REM in the treatment group were increased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). The contents of LH and FSH in the treatment group were significantly reduced(P<0.05), while the content of E_2 was significantly increased(P<0.05), and the changes were more significant than those in the control group(P<0.05). The incidence of adverse reactions in the control group was 8.8%, which was higher than 1.7% in the treatment group(P<0.05). Acupuncture combined with modified Xiangfu Decoction could significantly improve the sleep status of menopausal insomnia cases caused by liver Qi stagnation, with a lower incidence of adverse reactions, and so is worthy of clinical promotion and application.

[Tongjingling reduces ROS level and improves mitochondrial function in spermatogenic cells of varicocele rats with liver-qi stagnation].

OBJECTIVE: To explore the effects of the Chinese herbal compound Tongjingling (TJL) on the ROS level, mitochondrial membrane potential (MMP) and mitochondrial ultrastructure in spermatogenic cells in varicocele (VC) rats with liver-qi stagnation (LQS). METHODS: Totally, 72 male SPF Wistar rats were randomly divided into six groups of equal number, sham operation, VC+LQS model, low-, medium- and high-dose TJL, and L-carnitine (LC) control. The VC+LQS model was established by the Saypol method combined with tail-clamping. At 4 weeks after modeling, the rats in the low-, medium- and high-dose TJL groups were treated intragastrically with TJL at 0.6, 1.2 and 2.4 g/ml respectively, those in the sham operation and VC+LQS model groups with 0.9% saline, and those in the LC control group with LC oral liquid at 2.1 ml/kg, qd, for 8 weeks. Then the ROS level and MMP in the spermatogenic cells were measured by flow cytometry and the mitochondrial ultrastructure observed under the transmission electron microscope. RESULTS: The ROS level in the spermatogenic cells was significantly higher in the VC+LQS model and low-dose TJL groups than in the sham operation group (ï¼»62.72 ± 9.90ï¼½% and ï¼»52.25 ± 8.15ï¼½% vs ï¼»36.53 ± 5.25ï¼½%, P < 0.01), but remarkably lower in the medium-dose TJL (ï¼»41.65 ± 4.89ï¼½%), high-dose TJL (ï¼»39.60 ± 5.19ï¼½%) and LC control (ï¼»38.33 ± 7.46ï¼½%) than in the VC+LQS model group (P < 0.01). MMP in the spermatogenic cells was significantly lower in the VC+LQS model and low-dose TJL than in the sham operation group (ï¼»34.80 ± 20.18ï¼½% and ï¼»44.39 ± 19.60ï¼½% vs ï¼»60.24 ± 22.25ï¼½%, P < 0.01 and P < 0.05), but markedly higher in the medium-dose TJL (ï¼»50.62 ± 14.83ï¼½%), high-dose TJL (ï¼»52.42 ± 7.55ï¼½%) and LC control (ï¼»50.75 ± 15.65ï¼½%) than in the VC+LQS model group (P < 0.05). The mitochondria in the spermatogenic cells of the VC+LQS model rats exhibited swelling, vacuolization, rupture or disappearance of the mitochondrial cristae, and breakdown of the internal structure. The pathological injury of the mitochondrial structure was improved in different degrees in the TJL and LC groups. CONCLUSIONS: TJL can reduce the ROS level, increase MMP and improve pathological injury of the mitochondrial ultrastructure in the spermatogenic cells of VC rats with LQS, which may be the underlying molecular mechanism of TJL improving fertility in infertile VC patients.

The correlation between neurosteroids and neurotransmitters with liver yang rising and liver qi stagnation types of premenstrual syndrome.

BACKGROUND: To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS. METHODS: HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group). RESULTS: Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p < 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p < 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p < 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p < 0.05). CONCLUSION: The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.

Effect of the Early Start Denver Model on Children With Autism Spectrum Disorder Syndrome of Different Traditional Chinese Medicine Types in Northeast China.

Background: The clinical presentation of children with autism spectrum disorder (ASD) is heterogeneous, and there are little data available on the treatment of children with different types of ASD. We sought to explore which traditional Chinese medicine (TCM) syndrome type was more effective for children with ASD after 3 months of Early Denver Model intervention and to analyze the reasons for its efficacy from the perspective of TCM. Methods: This was a retrospective study. The subjects were children with ASD who were first diagnosed at the Developmental Behavioral Pediatrics, the First Hospital of Jilin University, between December 2018 and September 2019. Eighty-nine children were divided into a kidney jing deficiency group, a liver qi stagnation group, and a group with deficiency of both the heart and spleen. Results: After treatment, the total Autism Behavior Checklist (ABC), Autism Treatment Evaluation Checklist, and Childhood Autism Rating Scale scores were significantly reduced in the three groups (p < 0.05) compared to before treatment. Significant improvements were seen in all five domains of the Griffiths Development Scales-Chinese version in the LQ group (p < 0.05). After intervention, the LQ group showed greater improvements compared to the other two groups in the language, eye-hand coordination, body and object use, social and self-help, and total ABC scores. Conclusion: Our study showed that Early Denver Model intervention is effective in the treatment of three syndrome types of children with ASD, with the LQ group experiencing the most significant effects.

[Acupuncture combined with Heixiaoyao powder for children with cerebral palsy and its effect on serum immune indexes and nerve growth related protein].

OBJECTIVE: To observe the efficacy of acupuncture combined with Heixiaoyao powder for children with cerebral palsy (liver-qi stagnation, spleen-kidney deficiency syndrome) and its effect on serum immune indexes and nerve growth related protein. METHODS: A total of 180 children with cerebral palsy were randomly divided into a combined group (60 cases, 2 cases dropped off), an acupuncture group (60 cases, 4 cases dropped off) and a Chinese medication group (60 cases, 5 cases dropped off). On the basis of conventional treatment, the children in the combined group were treated with acupuncture [Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Benshen (GB 13), 30 min each time, twice a day] and Heixiaoyao powder; the children in the acupuncture group were treated with acupuncture, and the children in the Chinese medication group were treated with Heixiaoyao powder, the treatment was same with the combined group. All the children were treated for 6 consecutive days and rest for 1 day, totaling for 8 weeks. The Gesell developmental schedules (GDS) and TCM symptom scores were recorded before treatment, after treatment and at 3-month, 6-month and 12-month follow-up visit; the serum immune indexes (IgA, IgG and IgM) and nerve growth related protein [myelin basic protein (MBP), high mobility group box-1 (HMGB1), neuronspecific enolase (NSE)] were detected before and after treatment. The clinical efficacy of each group was evaluated. RESULTS: The total effective rate was 91.4% (53/58) in the combined group, which was higher than 80.4% (45/56) in the acupuncture group and 78.2% (43/55) in the Chinese medication group (P<0.05). Compared before treatment, the GDS scores in the three groups were increased and the TCM symptom scores were reduced after treatment and at 3-month, 6-month and 12-month follow-up visit (P<0.05). The GDS score in the combined group was higher than that in the acupuncture group and the Chinese medication group, and the TCM symptom score was lower than that in the acupuncture group and Chinese medication group (P<0.05). After treatment, the serum levels of IgA, IgG and IgM in the combined group were increased (P<0.05), and the serum levels of MBP, HMGBl and NSE were decreased (P<0.05), and the improvements were superior to those in the acupuncture group and the Chinese medication group (P<0.05). CONCLUSION: Acupuncture combined with Heixiaoyao powder could effectively improve the development quotient in children with cerebral palsy (liver-qi stagnation, spleen-kidney deficiency syndrome), regulate the serum immune indexes and nerve growth related protein levels.

A combination of depression and liver Qi stagnation and spleen deficiency syndrome using a rat model.

A syndrome (Zheng in Chinese) plays a critical role in disease identification, diagnosis, and treatment in traditional Chinese medicine (TCM). Clinically, the liver Qi stagnation and spleen deficiency syndrome (LQSSDS) is one of the most common syndrome patterns. Over the past few decades, several animal models have been developed to understand the potential mechanisms of LQSSDS, but until now, simulation of the syndrome is still unclear. Recently, several studies have confirmed that an animal model combining a disease and a syndrome is appropriate for simulating TCM syndromes. Overlapping previous studies have reported that depression is highly associated with LQSSDS; hence, we attempted to develop a rat model combining depression and LQSSDS. We exposed the rats to different durations of chronic unpredictable mild stress (CUMS). Subsequently, the evaluation indicators at macrolevel consisted of behavioral tests including open field test, sucrose preference test, and forced swim test, food intake, body weight, white adipose tissue, fecal water content, visceral hypersensitivity, and small bowel transit, and the evaluation indicators at microlevel included changes of hypothalamic-pituitary-adrenal axis. Serum D-xylose absorption was used to comprehensively confirm and assess whether the model was successful during the CUMS-induced process. The results showed that rats exposed to 6-week CUMS procedure exhibited significantly similar traits to the phenotypes of LQSSDS and depression. This study provided a new rat model for the LQSSDS and could potentially lead to a better understanding of the pathophysiology of LQSSDS and the development of new drugs for this syndrome.

[Effect on clinical symptoms and mechanism of chloasma in premenopausal women with liver qi stagnation treated with acupoint catgut embedding].

OBJECTIVE: To explore the therapeutic effect and mechanism of acupoint catgut embedding for chloasma in premenopausal women with liver qi stagnation. METHODS: A total of 92 patients of chloasma in premenopausal women with liver qi stagnation were randomized into an observation group and a control group, 46 cases in each one.In the observation group, acupoint catgut embedding was applied at Ganshu (BL 18), Pishu (BL 20), Sanyinjiao (SP 6), also the surrounding acupuncture was performed at facial part, once a week. In the control group, vitamin C (200 mg per time, 3 times a day) and vitamin E (100 mg per time, once a day) were prescribed for oral administration. Both of the two groups were given treatment for 12 weeks. The score of chloasma area and severity index (MASI), the serum levels of follicular stimulating hormone (FSH), leuteinizing hormone (LH) and estradiol (E2) before and after treatment were observed in the two groups, and the clinical effect of the two groups were compared after 3 months of treatment. RESULTS: Finally, 44 cases in the observation group and 43 cases in the control group completed the study. The effective rate in the observation group was 88.6% (39/44), which was higher than 55.8% (24/43) in the control group (P<0.01). Compared before treatment, the MASI scores after treatment were reduced in the two groups (P<0.01, P<0.05), the MASI score in follow-up in the observation group was reduced as compared with after treatment (P<0.01), and the MASI scores after treatment and in follow-up in the observation group were lower than the control group (P<0.01). Compared before treatment, the levels of FSH and LH in follow-up were reduced (P<0.01), there was no significant difference between before treatment and in follow-up in the level of E2 in the observation group (P>0.05). There was no significant difference between before treatment and in follow-up in the levels of FSH, LH and E2 in the control group (P>0.05). In follow-up, the levels of FSH and LH in the observation group were lower than the control group (P<0.01, P<0.05), there was no significant difference in the level of E2 between the two groups (P>0.05). CONCLUSION: Acupoint catgut embedding can improve the clinical symptoms of chloasma in premenopausal women with liver qi stagnation, the mechanism may be related to regulate the serum level of sex hormone to reduce high sensitivity of melanocytes to estrogen.

[Comparison of Therapeutic Effects Between Thermosensitive Moxibustion and Medication in the Treatment of Insomnia of Liver-Qi Stagnation Pattern].

OBJECTIVE: To compare the therapeutic effect of thermosensitive moxibustion (TSM) and medication in the treatment of insomnia patients with the syndrome of stagnation of liver-qi. METHODS: A total of 60 insomnia patients with the syndrome of liver-qi stagnation were randomly divided into TSM group and medication group (n ＝ 30 in each). Mild moxibustion was applied to bilateral Taichong (LR 3) and Qiuxu (GB 40) alternatively till the patient experienced an intense warmth (diathermic, heat transmission, etc.) feeling in the local region. The treatment was conducted once daily for 15 d. Patients of the medication group were ordered to take Estazolam tablets (1 mg/d) 1 h before sleeping, once daily for successive 15 days. The sleep quality (sleeping quality, falling asleep time, sleep duration, sleep efficiency, sleep disorders, hyponotic and day time dysfunction, 0－21 points) was evaluated by using Pittsburgh Sleep Quality Index (PSQI). The therapeutic effect was assessed in accordance with the "Guide Principles for Clinical Trials on New Drugs of Chinese Materia Medica (1993)" and international united sleep efficiency value. RESULTS: Following the treatment, the PSQI of both groups were significantly decreased relevant to their own pre-treatment (P<0.05), but without significant difference between the two groups (P>0.05). Of the two 30 cases in the medication and moxibustion groups, 12 (40.00%) and 20 (66.67%) had marked improvement, 7 (23.33%) and 6 (20.00%) were effective, and 11(36.67%) and 4 (13.33%) were invalid, with the effective rates being 63.33 % (19/30) and 86.67% (26/30), respectively. The effective rate of the TSM group was significantly higher than that of the medicine group (P <0.05). CONCLUSION: Thermosensitive moxibustion applied to the source points of the Liver and Gallbladder Meridians can improve the quality of sleep in insomnia patients with syndrome of liver-qi stagnation.

Effectiveness of Acupuncture Therapy on Stress in a Large Urban College Population.

This study is a randomized controlled clinical trial to study the effectiveness of acupuncture on the perception of stress in patients who study or work on a large, urban college campus. The hypothesis was that verum acupuncture would demonstrate a significant positive impact on perceived stress as compared to sham acupuncture. This study included 111 participants with high self-reported stress levels who either studied or worked at a large, urban public university in the southwestern United States. However, only 62 participants completed the study. The participants were randomized into a verum acupuncture or sham acupuncture group. Both the groups received treatment once a week for 12 weeks. The Cohen's global measure of perceived stress scale (PSS-14) was completed by each participant prior to treatment, at 6 weeks, at 12 weeks, and 6 weeks and 12 weeks post-treatment completion. While participants of both the groups showed a substantial initial decrease in perceived stress scores, at 12 weeks post treatment, the verum acupuncture group showed a significantly greater treatment effect than the sham acupuncture group. This study indicates that acupuncture may be successful in decreasing the perception of stress in students and staff at a large urban university, and this effect persists for at least 3 months after the completion of treatment.

Roles of the µ-opioid receptor and its related signaling pathways in the pathogenesis of premenstrual syndrome liver-qi stagnation.

The present study aimed to investigate the roles of the µ-opioid receptor (MOR) and its related signaling pathways in the pathogenesis of premenstrual syndrome (PMS) liver-qi stagnation, along with the therapeutic effects of the Shu-Yu capsule in treating the condition. A PMS liver-qi stagnation rat model was established using a chronic restraint stress method. The protein expression level of MOR within rat hippocampal tissue was detected via western blot analysis and cyclic adenosine monophosphate (cAMP) levels within the supernatant of a rat hippocampal cell culture were determined by ELISA. The western blot analysis indicated that the hippocampal expression level of MOR was significantly elevated in the PMS liver-qi stagnation model group. However, subsequent treatment with a Shu-Yu capsule was found to significantly decrease the level of MOR expression. In addition, in vitro experiments were performed, whereby primary hippocampal neurons were treated with model rat serum. It was observed that the level of MOR expression was significantly elevated, while brain-derived neurotrophic factor (BDNF) and cAMP levels in the culture supernatant were significantly decreased. These effects were reversed by treatment with serum from the Shu-Yu capsule-treated rats. Furthermore, when treated with the MOR activator DAMGO, the following were significantly decreased in the primary neurons: Phosphorylation levels of cAMP response element binding protein and extracellular signal-regulated protein kinases (ERK); BDNF expression; and cAMP content in the culture supernatant. These effects were reversed in primary neurons treated with DAMGO and Shu-Yu-containing rat serum. Collectively, the data suggest that increased MOR expression and activation of the cAMP/ERK signaling pathway in the hippocampus may be involved in the pathogenesis of PMS liver-qi stagnation. Furthermore, the efficacy of the Shu-Yu capsule in treating the condition may be via its regulation of MOR receptor signaling.