[Effects of Chinese herbal medicine Bushen Gubiao Recipe on toll-like receptor 4 and CD4(+)CD25(+)foxp3(+) regulatory T cells in mice with recurrent respiratory tract infections].

OBJECTIVE: To evaluate the effects of Bushen Gubiao Recipe (BGR), a compound traditional Chinese herbal medicine, on toll-like receptor 4 (TLR4) signaling pathway and CD4(+)CD25(+)foxp3(+)regulatory T cells (CD4(+)CD25(+)foxp3(+)Tregs) in mice with recurrent respiratory tract infections (RRTIs). METHODS: A mouse model of kidney-yang deficiency which simulated physical characteristics of RRTIs was established by intraperitoneal injection of hydrocortisone for 14 d. The model mice were divided into 4 groups, model group, high-dose BGR group, low-dose BGR group, and nucleic acid and casein oral solution group. They were administered respectively with distilled water, high-dose BGR (50 g/kg body weight), low-dose BGR (25 g/kg body weight) and nucleic acid and casein oral solution. Besides, a normal control group was set up and gastrogavage with distilled water. The effect of intervention was evaluated 4 weeks later by estimating the changes in behaviors of mice. Expressions of TLR4 and nuclear factor-kappa B (NF-κB) p65 in lung tissue were detected by immunohistochemical SABC method, the expression of TLR4 mRNA in lung tissue was detected by fluorescence quantitative-polymerase chain reaction (FQ-PCR), and the level of blood CD4(+)CD25(+)foxp3(+) Tregs was determined by flow cytometry. RESULTS: A kidney-yang deficiency mouse model with RRTIs was successfully established by intraperitoneal injection of hydrocortisone. BGR could improve the abnormal behavioral condition of the mice and enhance the expressions of TLR4 and NF-κB p65 in the lung tissue. Expression of TLR4 mRNA in high-dose BGR group was higher than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). Levels of CD4(+)CD25(+)foxp3(+)Tregs in high-dose BGR group and nucleic acid and casein oral solution group were lower than that in model group (P<0.05), while the difference was not statistically significant between high-dose BGR group and low-dose BGR group (P>0.05). CONCLUSION: BGR can improve the behavior of the kidney-yang deficiency mice, and improve the innate immune function by up-regulating TLR/NF-κB signaling pathway. BGR can adjust the immune imbalance of T-helper cell (Th) 1/Th2 through reducing the activity of CD4(+)CD25(+)foxp3(+)Tregs and enhancing the immune response of Th1 type.

Clinical research into Qufeng Zhidong Recipe used to treat 31 children with tic disorder.

OBJECTIVE: To assess the therapeutic effect and adverse reaction of Qufeng Zhidong Recipe (a recipe for dispelling wind to stop abnormal movement) used to treat children with tic disorder (TD). METHODS: The enrolled patients were randomized into a TCM group (31 cases) treated with Qufeng Zhidong Recipe and a Western medicine group (30 cases) treated with haloperidol and trihexyphenidyl. Two courses of treatment were observed with 12 weeks as one course. The therapeutic effect and adverse reaction were assessed with Yale Global Tic Severity Scale (YGTSS), Tic Symptom Score Scale (TSSS), TCM Syndrome Score Scale (TCMSSS), Treatment Emergent Symptom Scale (TESS) and laboratory examinations. RESULTS: The total effective rate was 100% in the TCM group and 60% in the Western medicine group with statistical significance in difference (P < 0.05). All the scores in the TCM group were better than those in the Western medicine group (P < 0.05). CONCLUSION: Qufeng Zhidong Recipe can obviously relieve the symptoms and signs of TD children without toxic side-effects.

Multicenter clinical study on the treatment of children's tic disorder with Qufeng Zhidong Recipe.

OBJECTIVE: To assess the effect and adverse reaction of Qufeng Zhidong Recipe (QZR) in treating children's tic disorder (TD). METHODS: With multicenter randomized parallel open-controlled method adopted, the patients enrolled were assigned to two groups, 41 cases in the Chinese medicine (CM) group and 40 in the Western medicine (WM) group. They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course. In total, two courses of treatment were given. The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale (YGTSS), Traditional Chinese Medicine Syndrome Scale (TCMSS), and Treatment Emergent Symptom Scale (TESS), as well as results of laboratory examinations. RESULTS: After one course of treatment, the markedly effective rate in the CM and the WM group was 14.6% and 17.5%, respectively, and the total effective rate 43.9% and 47.5%, respectively, which showed insignificant difference between groups (P>0.05). However, after two courses of treatment, markedly effective rate in them was 73.2% and 7.5%, and the total effective rate was 100.0% and 57.5%, both showing significant differences between groups (P<0.05). Besides, the adverse reactions occurred in the CM group was less than that in the WM group obviously. CONCLUSION: QZR has definite curative effect with no apparent adverse reaction in treating TD, and it can obviously improve the symptoms and signs and upgrade the quality of life and learning capacities in such patients.

[Effect of qufeng zhidong recipe on neuroethology and mRNA expressions of Notch1 and D2R in mouse with tic disorder].

OBJECTIVE: To evaluate the effect of Qufeng Zhidong Recipe (QZR) on the head tic behavior, and the mRNA expressions of Notch1 and dopamine D2 receptor (D2R) in tic disordered mice. METHODS: Mouse model like wet-dog shake head tic disorder was established by peritoneal injection of 5-HT2A/C agonist DOI for 14 successive days. The model mice were divided into three groups, the model group, the Chinese medicine (CM) treated group and the Western medicine (WM) treated group, they were intervened respectively with distilled water, QZR (10 g/kg) and haloperidol (1 mg/kg). Besides, a normal control group was set up and gastrogavaged with distilled water. The effect of intervention was evaluated 2 weeks later by estimating the head tic and the creeping distance of animals, and the mRNA expressions of D2R and Notch1 in corpus striatum and prefrontal cortex regions were detected using Real-time PCR. RESULTS: The wet-dog shake response and the creeping distance of mice were significantly reduced after intervention in both intervened groups, showing insignificant difference between the effects of CM and WM (P > 0.05). The expression of D2R mRNA in corpus striatum was higher than that in the prefrontal cortex (P < 0.01), at the prefrontal cortex, it was 151 +/- 30 in the CM group and 180 +/- 41 in the WM group, and at the corpus striatum, 710 +/- 64 and 850 +/- 80 respectively, all higher than those in the model group (P < 0.05). While the Notch1 mRNA expression in model mice were lower at the prefrontal cortex than at the corpus striatum (P < 0.05). After intervention it was 55 +/- 20 in the CM group and 48 +/- 23 in the WM group at the prefrontal cortex, all significantly lower than that in the model group (P < 0.05). CONCLUSION: DOI-induced wet-dog shake response could well simulate the clinical characteristics of tic disorder; QZR could improve the tic behavior and creeping distance in the model mice. The up-regulation of D2R mRNA expression after QZR intervention may be related with the down-regulation of Notch1 expression, this findings is worthy of further studies.

[A pathogenesis study of tic disorder in children based on pathogen incubation theory].

Pathogen incubation theory includes "no manifestation after infection" and "manifestation after incubation". Clinical data showed that the incidence and recurrence of tic disorders in children had a strong relevance to six exogenous factors. The pathogenesis is similar to the pathogenic mechanism based on incubation of pathogen theory, so we proposed a theory of "tic disorder induced by incubation of pathogen". Pathogenic wind can be classified into exterior wind and endogenous wind. Pathogenic wind is more apt to move, rise and migrate. The characteristics of pathogenic wind, especially easy mobility, determine the symptoms and signs of tic disorder, for pathogenic wind can be characterized by vibration and involuntary movement such as convulsion and tremor. If exogenous pathogenic wind moves into half-exterior and half-interior phase from the exterior, both the exterior and interior syndromes should be treated at the same time. We should regulate the function of the liver and the lung, expel pathogenic wind by dispersing the lung, and calm endogenous wind by removing obstruction in the collaterals and soothing the liver.

[Effect of sour TCM compound recipe on insulin resistance in experimental rats with diabetes mellitus type 2].

OBJECTIVE: To study the effect of sour TCM compound Recipe (SCCR) on insulin resistance in experimental rats with diabetes mellitus type 2 (DM2), under the guidance of TCM doctrine of "sour restrains sweet". METHODS: Model rats of DM2 were established by 8 weeks' feeding with high calorie forage combined with intraperitoneal injection of small dose of streptozotocin, and treated with SCCR (15 g/kg of crude drug/day). Levels of fasting blood glucose (FBG), serum insulin, free fatty acids (FFA), tumor necrosis factor a (TNF-alpha), combining capacity and constant of insulin receptor in liver were determined before treatment and 4, 8 and 12 weeks after treatment, and the insulin sensitive index was calculated. The data were compared with those in the model group (untreated), sweet TCM compound recipe group and bitter TCM compound group (treated with sweet and bitter Chinese drugs respectively) and the control group (treated with dimethyldiguanide). RESULTS: SCCR could markedly reduce the FBG, serum FFA and TNF-alpha levels in rat model of DM2, stimulate the secretion of insulin, raise the combining capacity and constant of insulin receptor in liver and improve the insulin sensitivity, as compared with the effect of sweet or bitter Chinese compound recipe, the difference was significant (P < 0.05). CONCLUSION: SCCR could improve the glucose metabolic disorder and ameliorate the degree of insulin resistance in DM2 model rats, with the effect superior to those with sweet or bitter taste, which illustrates primarily that the therapeutic principle of "sour restrains sweet" of TCM is true of science in a certain degree and having its guiding significance in clinical practice.