Lipo/TK-CDN/TPP/Y6 nanoparticles inhibit cutaneous melanoma formation.

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.

Comparing the efficacy of non-invasive physical therapy in improving pain and joint function of knee osteoarthritis: A protocol for systematic review and network meta-analysis.

BACKGROUND: The incidence of knee osteoarthritis is increasing year by year, which seriously affects people's quality of life, especially the elderly, and has become a major public health problem. A lot of evidence shows that physical therapy has advantages in the treatment of knee joints, but there are a number of physical therapy schemes, and the efficacy of each scheme is different. This study will evaluate the clinical efficacy of different physical therapy regimens in the treatment of knee osteoarthritis (KOA) by means of network meta-analysis. METHODS: According to the search strategy, we will retrieve the randomized controlled studies of non-invasive physical therapy in the treatment of knee osteoarthritis from CNKI, Wanfang, VIP, China Biomedical medicine, PubMed, Embase, Web of Science, and The Cochrane Library databases. The retrieval time was from the establishment of the database to March 2021. We will assess the quality of the studies using the Cochrane Risk Bias Assessment Tool and assess the strength of the evidence using the GRADE methodology. All data analyses will be performed by RevMan5.3, GEMTC 0.14.3, and Stata 14.0. RESULTS: This study will evaluate the efficacy of different physical therapy in the treatment of knee osteoarthritis by evaluating the total response rate, pain relief degree, joint function score, quality of life score, adverse reactions, etc. CONCLUSIONS: This study will provide a reliable evidence-based basis for the selection of better physical therapy for the treatment of knee osteoarthritis. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/VX98B.

[Effect observation of float needle combined with reperfusion activity for pain induced by cyclomastopathy].

OBJECTIVE: To observe the clinical effect of float needle therapy combined with reperfusion activity for pain induced by cyclomastopathy. METHODS: Thirty-five female patients with cyclomastopathy were randomly divided into a comprehensive group (18 cases) and a float needle group (17 cases). In the comprehensive group, float needle manipulation was used at the centre of the biceps brachii belly or the ligature between the affected nipple and breast nodule, about 4 cm beside the exterior margin of the breast, and the reperfusion activity of the affected upper limb and breast was combined. In the float needle group, simple float needle therapy was adopted. In the two groups, treatment was started 7 ± 3 days before menstruation, once every other day. After 3-time treatment, the changes of short form McGill Pain Questionnaire (SF-MPQ) scores before and after treatment, the time of pain relieved during the first treatment, recurrence in 3 months after treatment and the adverse reaction were observed. Also, the clinical effects of the two groups were compared. RESULTS: Immediately at the end of the first treatment,after 3-time treatment and while followed up for one month, each item score and the total score of SF-MPQ were decreased apparently than the scores before treatment (all P < 0.05), and all the scores mentioned above of the comprehensive group were declined more obviously than those of the float needle group (all P < 0.05). The time of pain relieved during the first treatment of the comprehensive group was much shorter than that of the float needle group [(94.72 ± 33.67) s vs (162.06 ± 29.16) s, P < 0.01]. The recurrence rate of the comprehensive group in 3 months after treatment was 5.9% (1/17), which was better than 20.0% (3/15) of the float needle group (P < 0.01). CONCLUSION: Float needle therapy combined with reperfusion activity and simple float needle therapy can both safely and effectively improve cyclomastopathy, and the combination therapy is better than simple float needle therapy in the aspects of pain relieving effect at once and the long term effect.

[Review on the role of Fu's subcutaneous needling (FSN) in pain relieving].

Through retrieval of all medical journals of CNKI and VIP from Jan. 1996 to Oct. 2012, ninety-nine articles were selected and analyzed. The result shows that reliable effect can be found in pain relieving, especially in pain of muscles and soft tissues. In mechanism research, action mechanism of Fu's subcutaneous needling (FSN) on pain relieving is expounded through theory of traditional medicine and modern medicine. Although the effect of FSN on pain relieving has been confirmed by numerous clinical trials, it is still lack of explanation on mechanism revealing. The further studies should focus on mechanism expounding, improving research methods and selecting more objective and reasonable evaluation system. Therefore, the effectiveness and scientificalness of FSN can be further enhanced.