Gold nanocages with dual modality for image-guided therapeutics.

Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.

[Randomized controlled clinical trials of individualized treatment of cerebral palsy children by warm-reinforcing needling combined with Bobath rehabilitation training].

OBJECTIVE: To observe the effect of warm-reinforcing needling combined with modern rehabilitation training on motor function of cerebral palsy (CP) children. METHODS: Sixty cases of CP children were randomly divided into acupuncture combined with rehabilitation (Acu + Rehab, n = 30) group and Rehab (n = 30) group. Patients of the Acu + Rehab group were treated by warm-reinforcing needling stimulation of Jiaji (EX-B 2), Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36), Yinlingquan (GB 34), Sanyinjiao (SP 6), Juegu (GB 39), Yanglingquan (GB 34), etc., combined with Bobath rehabilitation therapy, and those of the Rehab group treated by Bobath rehabilitation (stimulating key control points in the body, triggering reflexes that provide head and body control). The treatment was conducted every day,with three months being a therapeutic course,two courses in all. The Peabody Developmental Motor Scales 2 (PDMS-2) was used to evaluate the CP children's motor function [1) gross motor: posture (straightness ratio), locomotion and object manipulation; 2) fine motor: grasping and visual-Motor integration]. RESULTS: After the treatment, of the 30 and 30 cases in the Acu+ Rehab and Rehab groups, 1 (3.33%) and 0 (0%) were cured, 20 (66.67%) and 18 (60.00%) experienced marked improvement, 9 (30.00%) and 12 (40.00%) were invalid, with the effective rates being 70.00% and 60.00% respectively. The therapeutic effect of the Acu + Rehab group was markedly superior to that of the Rehab group (P < 0.05). After 6 months ' treatment, the scores of posture, locomotor, object manipulation and grasping, and visual-movement integration were significantly increased in comparison with pre-treatment in the same one group (P < 0.05), and the effects of the Acu + Rehab group were obviously superior to those of Rehab group in increasing the scores of posture, locomotor, object manipulation and grasping after 6 months' treatment (P < 0.05). CONCLUSION: Warm-reinforcing needling combined with Bobath rehabilitation has a better therapeutic effect in improving gross motor and fine motor functions of CP children.

[Effects of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke: a randomized and controlled study].

OBJECTIVE: To verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke. METHODS: Eighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment. RESULTS: The effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05). CONCLUSION: There is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training.

[Effect of heat-reinforcing needling combined with rehabilitation training on the motor function of ischemic stroke patients].

OBJECTIVE: To observe the therapeutic effect of heat-reinforcing needling combined with modem rehabilitation training on the motor function of ischemic stroke patients. METHODS: Fifty case of ischemic stroke patients were randomly divided into rehabilitation (Rehab, n=40) and acupuncture (Acup) + Rehab (n=40) groups. Heat-reinforcing needling was applied to Jianyu (LI 15), Quchi (LI 11), Hegu (LI 14), Zusanli (ST 36), Yanglingquan (GB 34), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once daily for 3 weeks. Rehabilitation training including healthy limb and joint movement was conducted, once daily for 3 weeks. The patient's neurological impairment degree and the motor function (Fugl-Meyer index) were evaluated before and after the treatment. RESULTS: After the treatment, of the each 40 cases in Rehab and Acup + Rehab groups, 10 (25.0%) and 17 (42.5%) experienced marked improvement in their symptoms, 17 (42.5%) and 18 (45.0%) had improvement, 13 (32.5%) and 5 (12.5%) failed, with the effective rates being 67.5% and 87.5% respectively. The therapeutic effect of Acup + Rehab group was markedly superior to that of Rehab group (P<0.05). Comparison between two groups showed no significant differences in the scores of clinical neurological impairment degree and the scores of Fugl-Meyer index before the treatment (P>0.05). After the treatment, the scores of neurological impairment degree of two groups both decreased significantly (P<0.05), and the scores of the Fugl-Meyer index of the upper and lower limbs increased significantly in two groups (P<0.05). The score of neurological impairment degree of Acup + Rehab group was significantly lower than that of Rehab group (P<0.05), while the scores of the Fugl-Meyer index of two limbs of Acup + Rehab group were obviously higher than those of Rehab group (P<0.01). CONCLUSION: The therapy of heat-reinforcing needling combined with rehabilitation training is significantly superior to that of simple rehabilitation training in improving neurological impairment and motor function of ischemic stroke patients.

[Clinical study of the treatment of infant cerebral palsy with warm-reinforcing needling combined with rehabilitation training].

OBJECTIVE: To observe the therapeutic effect of warm-reinforcing needling combined with modern rehabilitation training for infant cerebral palsy (CP). METHODS: Forty cases of cerebral palsy children were randomly divided into rehabilitation (Rehab, n=19) and acupuncture (Acup) + Rehab (n=21) groups. Body acupoints used were Baihui (GV 20), Zusanli (ST 36), Quchi (LI 11), Huantiao (GB 30), Yinlingquan (GB 34), Sanyinjiao (SP 6), etc., and scalp-acupoints Zhisanzhen (the cross-point between the anterior hairline and the median line of the head, 3 cun bilateral to the crossing point), Naosanzhen [Nao-hu (GV 17), 1.5 cun bilateral to GV17], Balance Zone, Motor Zone, etc. . The treatment was conducted once every other day, with 3 months being a therapeutic course, 2 courses altogether. Rehabilitation training included physical training (PT), occupational therapy (OT) training, and speech training (ST), 5 times a week, with 3 months being a therapeutic course, 2 courses altogether. Gross motor function measure (GMFM) and comprehensive function (CF, including cognition, speech, motor, self-care and social-adaptable abilities) were evaluated. RESULTS: After the treatment, of the 19 and 21 cases in Rehab and Acup+ Rehab groups, 12 (63.16%) and 18 (85.71%) experienced marked improvement, 7 (36.84%) and 3 (14.29%) failed, with the effective rates being 63.16% and 85.71% respectively. The therapeutic effect of Acup+ Rehab group was markedly superior to that of Rehab group (P < 0.05). Self-comparison of two groups showed that the scores of CF and GMFM increased significantly in comparison with pre-treatment (P < 0.01), and the scores of F and GMFM of Acup + Rehab group were obviously higher than those of Rehab group (P < 0.01). CONCLUSION: Rehabilitation training combined with acupuncture can apparently improve CP children's motor and comprehensive functions, and the therapeutic effect of AcupWarm-reinf Rehab is evidently superior to that of simple rehabilitation training therapy.

[Experimental study on the prevention and treatment effects of warm-reinforcing needling for hyperlipoidemia in the rabbit].

OBJECTIVE: To investigate the effect of warm-reinforcing needling (WRN) on serum lipid metabolism in hyperlipoidemia (HL) rabbits. METHODS: A total of 32 rabbits were randomly and evenly divided into control group, WRN group, model group and uniform reinforcing-reducing needling (URRN) group. HL model was established by feeding the rabbits with hypercholesterol and high-fat forage continuously for 7 weeks. For rabbits of WRN and URRN groups, "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Xuehai" (SP 10) were punctured and stimulated manually with WRN and URRN techniques respectively, once daily, continuously for 7 weeks. At the end of experiments, blood samples were collected from the heart, and centrifuged for detecting serum total cholesterol (TC) triglyceride (TG) and high density lipoprotein (HDL) with enzyme method, and platelet aggregation rate (PAR) with an intelligent blood agglutometer. Low density lipoprotein (LDL) = TC- (HDL + TG/2.2). RESULTS: Compared with normal control group, serum TC, TG and LDL contents in model group, WRN and URRN groups increased significantly (P < 0.01), and HDL content of model group decreased considerably (P < 0.01); while in comparison with model group, serum TC, LDL and TG contents of WRN and URRN groups decreased considerably (P < 0.01), and serum HDL levels of WRN and URRN groups increased significantly (P < 0.01). Serum TC content of WRN group was markedly lower than that of URRN group (P < 0.05), and HDL of WRN group was remarkably higher than that of URRN group (P < 0.01). In comparison with normal control group, 1 min, 5 min and maximum PARs in model, WRN and URRN groups increased significantly (P < 0.01), while in comparison with model group, 1 min, 5 min and maximum PARs of WRN and URRN groups decreased considerably (P < 0.01). In addition, 1 min and maximum PARs in WRN group were markedly lower than those in URRN group (P < 0.05). Light microscopic observation showed that the apoptotic foam cells in the lipid plaque of aorta wall in model group appeared and were obviously more than those of WRN and URRN groups. CONCLUSION: Acupuncture can effectively lower serum TC, LDL and TG levels, raise serum HDL content, and suppress platelet aggregation, and the therapeutic effect of WRN is significantly superior to that of URRN, which may contribute to the action of acupuncture in regulating blood lipid and inhibiting the formation of atheromatous plaque.

[Protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms].

OBJECTIVE: To explore the influence of psychological factor on asthma, the protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms. METHODS: Allergy and stress-induced asthma models were established in rats by giving ovalbumin and restraining stress. Radioimmunoassay, enzyme linked immunosorbent assay, in situ hybridization and immunohistochemical method were used to detect plasma corticosterone, IL-4, IFN-gamma, expression of glucocorticoid receptor (GR) mRNA in hippocampus and adrenocorticotropic hormone corticoliberin (CRH) positive neuron in hypothalamus. Optical and electron microscopes were used to observe the morphological changes of pulmonary hilar and hippocampal tissues. RESULTS: Shugan Lifei Recipe (SGLFR) could reduce plasma corticosterone, decrease CRH positive neurons in paraventricular nucleus of hypothalamus, up-regulate the expression of GR mRNA in hippocampus and reduce the injury of hippocampal neuron. SGLFR had certain inhibitive effect on hyperfunction of hypothalamo-pituitary-adrenal cortex (HPA) axis in rats with asthma under stress and could also relieve the pathological changes of the pulmonary hilar tissue. The level of plasma IFN-gamma was increased while the level of plasma IL-4 was decreased in SGLFR-treated group. CONCLUSION: The mechanism of SGLFR in treating the rats with asthma under stress is probably to regulate the hyperfunction of HPA axis and the disorder of immuo-system.

[Experimental study of apoptosis and proliferation of gastric mucosal cells in chronic atrophic gastritis].

OBJECTIVE: To study the relationship between long-term high-salt hot diet and chronic atrophic gastritis (CAG). The expression of apoptosis cells, proliferation cells, bcl-2 and Fas proteins were detected in the gastric mucosa of CAG rates induced by high-salt hot water. METHODS: TUNEL technique and immunohistochemical method were used in the experiment. Flow cytometry method was used to detect the DNA content of apoptosis cells. RESULTS: (1) The detection of apoptosis with TUNEL showed that the apoptosis cells in CAG rates induced by high-salt hot water were high. These cells could be seen in all layers of gastric mucosa, apoptosis index of model rates was higher than that of normal rates (P < 0.05). (2) The result of detecting apoptosis gene and proliferating cell nuclear antigen (PCNA) by immunohistochemical method showed that the expression of bcl-2, Fas and PCNA in the CAG rates induced by high-salt hot water was much higher than that of normal gastric mucosa (P < 0.05). The expression rates of bcl-2, Fas proteins were higher with time going on. After being given high-salt hot water intragastrically for 4, 8, 12 weeks, the bcl-2 protein expression rates were 12.5%, 16.7%, 76.5%, the Fas protein expression rates were 18.7%, 22.2% and 64.7%. (3) Flow cytometry technique showed that there was a second G(0)/G(1) peek, which was apoptosis cells peak, but was not seen in the normal gastric mucosa. CONCLUSIONS: Abnormality of proliferation and apoptosis in gastric mucosa could be induced by high-salt hot water. bcl-2, Fas gene played an important role in this course.