Regulation of IFP in solid tumours through acoustic pressure to enhance infiltration of nanoparticles of various sizes.

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

[Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial].

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION: Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

[Effect of electroacupuncture at back-shu points of five zang on fatigue status and cortical excitability in chronic fatigue syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. METHODS: A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. RESULTS: After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05). After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). CONCLUSION: EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex.

[FU Wen-bin's experience in treatment of depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder].

Based on the thinking of integrative and holistic acupuncture and moxibustion, FU Wen -bin proposes to treat depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder. In clinical practice, the treatment pattern of "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" is applied, acupuncture, refined moxibustion, intradermal needle and other therapies are comprehensively adopted, acupoints on the heart meridian, pericardium meridian and gallbladder meridian are selected or back-shu points and front-mu points of the heart, gallbladder and pericardium are matched, and the acupoints on the conception vessel and governor vessel and with the functions of tonifying kidney and regulating qi are added to calm the heart and tranquilize the mind, so as the symptoms of depression and obsessive-compulsive can be effectively relieved.