Tumor-Targeted Injectable Double-Network Hydrogel for Prevention of Breast Cancer Recurrence and Wound Infection via Synergistic Photothermal and Brachytherapy.

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)-alginate double-network nanocomposite hydrogel (GPA) embedded with 125 I-labeled RGDY peptide-modified gold nanorods (125 I-GNR-RGDY) is fabricated. The double-network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature-induced PEGDA polymerization driven by near-infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double-network hydrogel possesses a dense polymer network and tightly fixes 125 I-GNR-RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self-repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single-photon emission computerized tomography imaging owing to isotope labeling of loaded 125 I-GNR-RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.

Effect of integrated Traditional Chinese and Western Medicine on gout.

OBJECTIVE: To evaluate the curative effect of integrated Traditional Chinese and Western Medicine on gout, and to investigate the therapy timing and exact treatment options of integrated medicine. METHODS: Totally 860 patients were enrolled, including 460 patients with intermittent gout, 200 patients with active Traditional Chinese Medicine (TCM) syndrome (TCM syndrome score ≥ 6) and 200 patients with stable TCM syndrome (score < 6). They were randomly divided into intervention and control groups. The control group was treated according to Western Medicine guidelines. The intervention group was treated with integrated Traditional Chinese and Western Medicine. The efficacy of TCM syndrome, joint pain score, joint swelling score, ESR, C-reactive protein, serum uric acid, liver and kidney function, and the duration of remission of TCM syndrome were compared between the two groups before and after treatments. RESULTS: For the patients with stable TCM syndrome, there was no significant difference in the effective rate and inefficiency between the intervention group and the control group. For the active type, the effective rate of the intervention group is better than the control group significantly. For the stable type, there was no significant difference between the intervention group and the control group in improving the scores of joint pain and swelling, reducing the level of ESR, C-reactive protein, serum uric acid and improving liver and kidney function. For the active type, the differences between the two groups were significant. The stable stage of gout in the intervention group was longer than the control group. CONCLUSION: For the gout patients with stable TCM syndrome in the acute stage of gout, we can use TCM treatment or Western Medicine alternatively; for the patients with active TCM syndrome, the scheme of combination of Traditional Chinese and Western Medicine can be applied, with the better curative effect than any medicine alone.

Efficacy of Acupuncture-Related Therapy in the Treatment of Knee Osteoarthritis: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Knee osteoarthritis (KOA) is prevalent in middle-aged and elderly people. This condition negatively affects the quality of life of patients. Although non-steroidal anti-inflammatory drugs (NSAIDs) are often used to relieve symptoms associated with KOA, it is associated with many side effects. Acupuncture and moxibustion therapies have been applied in the treatment of KOA. However, the efficacy of various acupuncture and moxibustion treatments has not been compared. METHODS: Randomized controlled trials (RCTs) on the application of acupuncture and moxibustion in the treatment of KOA were searched in English databases and Chinese databases. Data were retrieved from establishment of the database to September 2020. Data analysis was performed using Stata14.0 and GeMTC 0.14.3 softwares. RESULTS: A total of 40 RCTs involving 3215 patients with KOA were retrieved. Network meta-analysis revealed that the fire needle was superior to western medicine, electro-acupuncture, conventional acupuncture, warm needle and sham acupuncture; warm needle was better than conventional acupuncture and western medicine whereas electro-acupuncture was better than conventional acupuncture in improving pain scores in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Moreover, we found that fire needle and warm needle more effectively improved WOMAC stiffness scores than western medicine and sham moxibustion, whereas electro-acupuncture was superior to western medicine and sham moxibustion in improving WOMAC stiffness scores. Further analysis revealed that fire needle, warm needle and electro-acupuncture were more effective in improving WOMAC joint function scores than conventional acupuncture and western medicine. The fire needle was superior to conventional acupuncture and sham acupuncture, whereas electro-acupuncture was better than western medicine, conventional acupuncture and sham acupuncture in improving visual analogue scale scores. CONCLUSION: This study shows that fire needle is superior to warm needle and electro-acupuncture, whereas warm needle and electro-acupuncture are better than conventional acupuncture, western medicine, sham moxibustion and sham acupuncture.

Molecular mechanism of reproductive toxicity induced by Tripterygium Wilfordii based on network pharmacology.

ABSTRACT: To explore the possible molecular mechanism of reproductive toxicity of Tripterygium wilfordii from the perspective of network pharmacology and bioinformatics.The compounds of T wilfordii were obtained by querying the relevant Chinese medicine database, the effective compounds were screened and the corresponding targets were obtained, and then compared with the reproductive toxicities related to disease targets obtained from the disease gene database to infer the potential toxic targets of reproductive toxicity of T wilfordii. Then, the key targets of reproductive toxicity of T wilfordii were screened using Search Tool for the Retrieval of Interacting Genes/Protein and Cytoscape. The gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as module analysis, were performed on the key targets using Database for Annotation, Visualization, and Integrated Discovery and Cytoscape, respectively. Finally, the network between effective compounds-toxic targets was conducted to see how the compounds interacted.A total of 48 effective compounds and 482 potential toxic targets related to the reproductive toxicity of T wilfordii were screened. The enrichment analysis results showed that the key targets were mainly enriched in biological processes such as response to drug, ionotropic glutamate receptor signaling pathway, and KEGG pathways such as neuroactive ligand-receptor interaction, cAMP signaling pathway. In the protein-protein interaction network of potential toxic targets, there were 78 key targets such as TP53, INS, IL6, AGT, ADCY3, and so on. Enrichment analysis of the top module with 19 genes from module analysis indicated that T wilfordii might cause reproductive toxicity by gene ontology terms and KEGG pathways such as regulation of vasoconstriction, G-protein coupled receptor signaling pathway, inflammatory response, cAMP signaling pathway, and so on. In the network between effective compounds of T wilfordii and key targets, there were 5 compounds with high degree including Tingenone, Wilfordic Acid, Abruslactone A, Nobilin, and Wilforlide B.The complex molecular mechanism of reproductive toxicity of T wilfordii can be preliminarily elucidated with the help of the network pharmacology method, and the analysis results can provide some reference for the further mechanism research of reproductive toxicity of T wilfordii.

De Novo Design of Functional Coassembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization.

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lap nanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface area of PAH3 nanofibers after coassembly with Lap. Dynamic oscillatory rheology revealed that the coassembled PAH3-Lap hydrogels displayed high stiffness and robust self-healing behavior while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional (3D) matrix provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3D matrix. Applicability of the organic-inorganic PAH3-Lap hydrogels was assessed in vitro using human bone marrow-derived stromal cells (hBMSCs) and ex vivo using a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic-inorganic PAH3-Lap hydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls.

In vitro evaluation of MgSr and MgCaSr alloys via direct culture with bone marrow derived mesenchymal stem cells.

Magnesium (Mg) and its alloys have been widely investigated as the most promising biodegradable metals to replace conventional non-degradable metals for temporary medical implant applications. New Mg alloys have been developed for medical applications in recent years; and the concept of alloying Mg with less-toxic elements have aroused tremendous interests due to the promise to address the problems associated with rapid degradation of Mg without compromising its cytocompatibility and biocompatibility. Of particular interests for orthopedic/spinal implant applications are the additions of calcium (Ca) and strontium (Sr) into Mg matrix because of their beneficial properties for bone regeneration. In this study, degradation and cytocompatibility of four binary MgSr alloys (Mg-xSr, x = 0.2, 0.5, 1 and 2 wt%) and four ternary MgCaSr alloys (Mg-1Ca-xSr, x = 0.2, 0.5, 1 and 2 wt%) were investigated and compared via direct culture with bone marrow-derived mesenchymal stem cells (BMSCs). The influence of the alloy composition on the degradation rates were studied and compared. Moreover, the cellular responses to the binary MgSr alloys and the ternary MgCaSr alloys were comparatively evaluated; and the critical factors influencing BMSC behaviors were discussed. This study screened the degradability and in vitro cytocompatibility of the binary MgSr alloys and the ternary MgCaSr alloys. Mg-1Sr, Mg-1Ca-0.5Sr and Mg-1Ca-1Sr alloys are recommended for further in vivo studies toward clinical translation due to their best overall performances in terms of degradation and cytocompatibility among all the alloys studied in the present work. STATEMENT OF SIGNIFICANCE: Traditional Mg alloys with slower degradation often contain aluminum or rare earth elements as alloying components, which raised safety and regulatory concerns. To circumvent unsafe elements, nutrient elements such as calcium (Ca) and strontium (Sr) were selected to create Mg-Sr binary alloys and Mg-Ca-Sr ternary alloys to improve the safety and biocompatibility of bioresorbable Mg alloys for medical implant applications. In this study, in vitro degradation and cellular responses to four binary Mg-xSr alloys and four ternary Mg-1Ca-xSr alloys with increasing Sr content (up to 2 wt%) were evaluated in direct culture with bone marrow derived mesenchymal stem cells (BMSCs). The roles of Sr and Ca in tuning the alloy microstructure, degradation behaviors, and BMSC responses were collectively compared in the BMSC direct culture system for the first time. The most promising alloys were identified and recommended for further in vivo studies toward clinical translation.

[Efficacy Observation for Treating Ankylosing Spondylitis by Chinese Herbs and Recombinant Hu- man Tumor Necrosis Factor Receptor II-Antibody Fusion Protein].

OBJECTIVE: To observe the clinical effect of Chinese medical (CM) syndrome differentiation based Chinese herbs and recombinant human tumor necrosis factor receptor II-antibody fusion protein (etanercept) for treating ankylosing spondylitis (AS) patients. METHODS: Totally 35 AS patients were treated with syndrome differentiation based Chinese herbs and etanercept. Reinforcing Shen and strengthening Du channel, activating meridians to stop pain was principle used in syndrome differentiation based treatment. Etanercept was subcutaneously injected, 25 mg each time; twice per week for the first three months and once a week for the latter three months. The clinical efficacy was evaluated after 3 and 6 months of treatment. Meanwhile, ASAS20 and ASAS50 standards arriving rates were also observed. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), visual analog score (VAS) for spine pain, VAS for night pain, patient global assessment (PGA), VAS for physician global assessment, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, cervical rotation, Schober improved test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were observed before treatment, 3 and 6 months after treatment. RESULTS: Compared with before treatment, BASDAI, BASFI, VAS for spine pain, night pain, physician global assessment, PGA, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, Schober improved test, ESR, and CRP all decreased after 3 and 6 months of treatment, with statistical difference (P < 0.05). Cervical rotation also decreased after 6 months of treatment, with statistical difference (P < 0.05). Compared with 3 months of treatment, total effective rate of CM syndrome, ASAS20 and ASAS50 standards arriving rates increased after 6 months of treatment, with statistical difference (P < 0.05). There were statistical differences in all indices mentioned above between after 3 months of treatment and after 6 months of treatment (P < 0.05). CONCLUSION: Syndrome differentiation based Chinese herbs combined etanercept could alleviate inflammatory reaction favorably, control the progression of active AS, and improve joint functions.

A multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Tong Luo Hua Shi capsule, a modernized Tibetan medicine, in patients with rheumatoid arthritis.

BACKGROUND: Tong Luo Hua Shi (TLHS) is a new formulation of the traditional Tibetan medicine Wu-wei-gan-lu that has been used for the treatment of rheumatoid arthritis (RA) for hundreds of years in China. This study aimed to evaluate the efficacy and safety of TLHS in patients with RA. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding study performed in patients with active RA from five medical centers. Patients received three doses (4.8, 3.6, or 2.4 g/day po) of TLHS or placebo (tid po) for 8 weeks. Blood sampling, physical examination, and assessment of the American College of Rheumatology (ACR) 20 % improvement (ACR20) criteria were performed before and every 2 weeks after starting treatment. The primary endpoint was the ACR20. The secondary endpoints included safety. RESULTS: A total of 240 participants were screened and 236 patients were randomized (n = 59/group); 20 dropped out. After 8 weeks, ACR20 improvements in the TLHS 4.8 g and 3.6 g groups were significantly higher than in the placebo group (P < 0.01 and P < 0.05, respectively). ACR50 improvement in the TLHS 4.8 g group was significantly higher compared with the placebo group (P < 0.01). Symptoms of RA were significantly relieved in the TLHS groups. In the TLHS groups, insomnia (n = 1), gastroenteric reactions (n = 2), arrhythmia (n = 1), and minor hepatic lesion (n = 1) were reported; in the placebo group, hepatic dysfunction (n = 1) was reported (P = 0.878). CONCLUSIONS: TLHS improved the symptoms of patients with RA according to the ACR20. Moreover, TLHS was safe. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-12003871 . Registered on 1 January 2012.

[Clinical plan of acupuncture for sclerosis].

The literature regarding acupuncture for sclerosis in CNKI database, VIP database and Wanfang database from date of database establishment to April 1st, 2015 was retrieved. As a result, 26 articles of clinical researches and medical cases with significant efficacy were collected. It was found the methods and clinical plan of acu-puncture for sclerosis were various and distinctive, including filiform-needle acupuncture, electroacupuncture, bee acupuncture, fire acupuncture, moxibustion, herb moxibustion as well as acupuncture-moxibustion combined with cupping, hot compress, acupoint injection. It was concluded acupuncture-moxibustion combined with various methods could complement each other's strengths, and achieve synergistic effect. The efficacy was affirmative and the characteristics of TCM were significant, however, researches regarding the scientific normalization and stan-dardization of the clinical plan were needed.

[Clinical review of ankylosing spondylitis treated with acupuncture and medicine].

Thirty-two articles from January 2000 to December 2014,with ankylosing spondylitis treated by acupuncture,moxibustion and medicines(Chinese medicine or western medicine) and statistically significant and effective results,were collected through Chinese National Knowledge Infrastructure(CNKI),WANFANG and VIP databases. It is concluded that there are various methods except medicines treating ankylosing spondylitis,including acupuncture,acupuncture combined with moxibustion,warm acupuncture,electroacupuncture,apitherapy,fire needle therapy,etc. Further studies are needed to be implemented so as to promote the combination therapy of acupuncture and medicine for ankylosing spondylitis,such as the standard cases of the combination therapy and mechanism.

Metabolic regulatory and anti-oxidative effects of modified Bushen Huoxue decoction on experimental rabbit model of osteoarthritis.

OBJECTIVE: To observe the metabolic, regulatory and anti-oxidative effects of modified Bushen Huoxue Decoction (BSHXD), a Chinese herbal medicine for kidney (Shen)-reinforcement and blood-activation, on an osteoarthritis (OA) rabbit model. METHODS: A rabbit model for knee joint OA was established by the classic Hulth's method. The OA model rabbits were randomized into 5 groups: the model control group, the positive control group treated with glucosamine sulfate, and the three BSHXD treated groups treated respectively with low, moderate, and high doses of BSHXD. In addition, a normal control group and a sham-operated group were set up. Experimental animals were sacrificed after a 7-week treatment, and pathological changes in cartilaginous tissue were estimated using the Mankin criteria. Hydroxyproline (Hyp) and malonaldehyde (MDA) contents in blood serum and urine, as well as superoxide dismutase (SOD) activity and nitric oxide (NO) content in blood serum and knee joint synovial homogenates were detected. RESULTS: Mankin scoring showed insignificant statistical differences between the various treatment groups (P >0.05), but all were better than the model control group (P <0.05). Serum and urinary contents of Hyp and MDA as well as serum and synovial levels of NO were significantly lower, but the SOD activity in blood serum and synovial tissue was higher in the BSHXD treated groups than in the model group P <0.01); the effect of BSHXD was dose-dependent to some extent. CONCLUSION: The modified BSHXD shows an effect of improving cartilage metabolism in experimental rabbits with OA, and possesses osteo-chondric protective effects in antagonizing peroxidation injury.