Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

Effect of Acupuncture along Meridians on Pain Degree and Treatment of Acute Lumbar Sprain.

Aim: This study is aimed at investigating the effect of acupuncture along meridians on pain degree and treatment of acute lumbar sprain. Methods: A total of 96 patients with acute lumbar sprain from May 2019 to March 2021 in our hospital were selected and divided into the study and control groups. The patients in the control group were administered conventional western medicine and massage therapy, while the study group underwent acupuncture along meridians based on the control group. The therapeutic effect, visual analogue scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), and lumbar range of motion (ROM) scores, emG inversion times, emG amplitude of the sacrospinalis muscle, and the serum TNF-α and IL-6 levels were determined. Results: The total effective rate of the study group was significantly higher than that of the control group. After treatment, the VAS, RMDQ, and ROM scores of the study group were significantly lower than those of the control group. Before the intervention, the EMG inversion times and the EMG amplitude of the spinous process muscle in the study group were not significantly different from those in the control group. After the intervention, the number and amplitude of EMG reversal in the study group were significantly higher than those in the control group. After the intervention, the serum levels of TNF-α (pg/ml) and IL-6 (pg/ml) in the study group were significantly lower than those in the control group. Conclusion. Meridian acupuncture for acute lumbar sprain can effectively improve body function, relieve pain, regulate serum inflammatory factors, and improve the overall therapeutic effect.

Feature optimization based on improved novel global harmony search algorithm for motor imagery electroencephalogram classification.

Background: Effectively decoding electroencephalogram (EEG) pattern for specific mental tasks is a crucial topic in the development of brain-computer interface (BCI). Extracting common spatial pattern (CSP) features from motor imagery EEG signals is often highly dependent on the selection of frequency band and time interval. Therefore, optimizing frequency band and time interval would contribute to effective feature extraction and accurate EEG decoding. Objective: This study proposes an approach based on an improved novel global harmony search (INGHS) to optimize frequency-time parameters for effective CSP feature extraction. Methods: The INGHS algorithm is applied to find the optimal frequency band and temporal interval. The linear discriminant analysis and support vector machine are used for EEG pattern decoding. Extensive experimental studies are conducted on three EEG datasets to assess the effectiveness of our proposed method. Results: The average test accuracy obtained by the time-frequency parameters selected by the proposed INGHS method is slightly better than artificial bee colony (ABC) and particle swarm optimization (PSO) algorithms. Furthermore, the INGHS algorithm is superior to PSO and ABC in running time. Conclusion: These superior experimental results demonstrate that the optimal frequency band and time interval selected by the INGHS algorithm could significantly improve the decoding accuracy compared with the traditional CSP method. This method has a potential to improve the performance of MI-based BCI systems.

Rationally designed upconversion nanoparticles for NIR light-controlled lysosomal escape and nucleus-based photodynamic therapy.

Cell nucleus-based photodynamic therapy is a highly effective method for cancer therapy, but it is still challenging to design nucleus-targeting photosensitizers. Here, we propose the "one treatment, multiple irradiations" strategy to achieve nucleus-based photodynamic therapy using the photosensitizer rose bengal (RB)-loaded and mesoporous silica-coated upconversion nanoparticles with the surface modification of amine group (UCNP/RB@mSiO2-NH2 NPs). After implementation into cancer cells, the rationally designed UCNP/RB@mSiO2-NH2 NPs could be specifically accumulated in the acidic lysosomes due to their amino group-decorated surface. Upon a short-term (3 min) irradiation of 980 nm near-infrared light, the reactive oxygen species produced by RB through the Förster resonance energy transfer between the upconversion nanoparticles and RB molecules could effectively destroy lysosomes, followed by the release of the UCNP/RB@mSiO2-NH2 NPs from the lysosomes. Subsequently, these released UCNP/RB@mSiO2-NH2 NPs could be transferred into the cell nucleus, where a second 980 nm light irradiation was conducted to achieve the nucleus-based photodynamic therapy. The rationally designed UCNP/RB@mSiO2-NH2 NPs showed excellent anticancer performance in both two-dimensional and three-dimensional cell models using the "one treatment, multiple irradiations" strategy.

Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.

Optimized acupuncture treatment (acupuncture and intradermal needling) for cervical spondylosis-related neck pain: a multicenter randomized controlled trial.

ABSTRACT: Cervical spondylosis (CS)-related neck pain is difficult to treat because of its degenerative nature. The aim of this 9-center, single-blinded, randomized controlled trial was to evaluate the efficacy of optimized acupuncture for CS-related neck pain. Participants who met the inclusion criteria were randomized to optimized, shallow, and sham acupuncture groups (1:1:1). The primary outcome was the change from baseline in the Northwick Park Neck Pain Questionnaire score at week 4. Participants were followed up until week 16. Of the 896 randomized participants, 857 received ≥1 intervention session; 280, 286, and 291 received optimized, shallow, and sham acupuncture, respectively. A total of 835 (93.2%) participants completed the study. At week 4, significant differences (P < 0.001) were observed in the changes in Northwick Park Neck Pain Questionnaire scores between the optimized acupuncture group and both the shallow {7.72 (95% confidence interval [CI], 5.57-9.86)} and sham acupuncture (10.38 [95% CI, 8.25-12.52]) groups. The difference in the scores at week 16 between the optimized acupuncture group and the shallow (8.84 [95% CI, 6.34-11.34]) and sham acupuncture (10.81 [95% CI, 8.32-13.30]) groups were significant. The center effect indicated wide variability in the treatment effects (Cohen's d = 0.01-2.19). Most SF-36 scores were higher in the optimized acupuncture group than those in the other groups. These results suggest that 4-week optimized acupuncture treatment alleviates CS-related neck pain and improves the quality of life, with the effects persisting for minimum 3 months. Therefore, acupuncture can have positive effects on CS-related neck pain, although the effect size may vary widely.

Platinum-doped carbon nanoparticles inhibit cancer cell migration under mild laser irradiation: Multi-organelle-targeted photothermal therapy.

Tumor growth and metastasis are two main causes of cancer-related deaths. Here, we simultaneously investigated the effects of nanoparticles on cancer cell viability and migration using polyethylene glycol (PEG)-modified, platinum-doped (<4 mol %) carbon nanoparticles (denoted as PEG-PtCNPs). The bare PtCNPs were prepared by the facile one-step hydrothermal treatment of p-phenylenediamine and K2PtCl4 in aqueous solution. After PEGylation, the obtained PEG-PtCNPs can serve as an excellent photothermal nanoagent for cell migration inhibition, laser-triggered nuclear delivery, effective tumor accumulation, and imaging-guided tumor ablation with improved therapeutic efficacy and reduced side effects. In the absence of laser exposure, the positively charged PEG-PtCNPs with a hydrodynamic diameter of ∼19 nm easily entered the cells by endocytosis and were located in multiple organelles (including mitochondrion, endoplasmic reticulum, lysosome, and Golgi apparatus), causing a slight increase in the expression level of nuclear protein lamin A/C. Upon mild laser irradiation (0.3 W cm-2), the fragmented cytoskeletal structures and overexpression of lamin A/C were observed, thus inhibiting cancer cell migration. Furthermore, hyperthermia induced by PEG-PtCNPs plus laser irradiation at a higher power density (1.0 W cm-2) could cause irreversible damage to the nuclear membranes and then facilitate the nuclear delivery of the nanoagents without the introduction of nuclear targeting ligands. Taken together, this work develops a facile synthetic approach of platinum-based carbon nanoparticles with excellent photothermal properties, and demonstrates their potential applications for modulating tumor metastasis and realizing multi-organelle-targeted tumor ablation.

Randomized single-blind multicenter trial comparing the effects of standard and augmented acupuncture protocols on sleep quality and depressive symptoms in patients with depression.

The study was aimed to compare the effects of standard and augmented acupuncture on depressive symptoms and sleep disturbances in patients with depression. This is a randomized, single-blind, multicenter trial. 140 subjects with clinical insomnia (score of ≥ 7 on the Pittsburgh Sleep Quality Index (PSQI)) were randomized to the standard (LI4, LIV3, EX-HN3, and GV20) or augmented (LI4, LIV3, EX-HN3, GV20, LU7, and KID6, including intradermal needles for sustained treatment) acupuncture groups. Participants received two sessions weekly for six weeks. In trial, The primary outcomes were improvements in PSQI and the Hamilton Rating Scale (HAMD). Secondary outcomes were treatment credibility and adverse events. Outcomes were assessed at baseline, week 3, end of treatment, and 4-week follow-up. From the 105 randomized patients, 89 completed the trial and were included in the final analyses. Better efficacy was observed in the augmented group compared with the standard acupuncture to improve the PSQI and HAMD at week 3, end of treatment, and 4-week follow-up (all p < .05). The HAMD scores improved with time, except between end of treatment and 4-week follow-up, while in the standard group, HAMD scored improved from baseline to week 3, and stopped improving thereafter. The PSQI scores improved with time in the two groups, except between end of treatment and 4-week follow-up. Compared with the standard protocol, the augmented acupuncture protocol had a better efficacy to treat depression and to improve sleep quality of patients with depression.

[Chemical components from essential oil of Pandanus amaryllifolius leaves].

OBJECTIVE: To analyze the chemical compositions of Pandanus amaryllifolius leaves essential oil extracted by steam distillation. METHODS: The essential oil of Pandanus amaryllifolius leaves was analyzed by gas chromatography-mass spectrum, and the relative content of each component was determined by area normalization method. RESULTS: 128 peaks were separated and 95 compounds were identified, which weighed 97.75%. The main chemical components of the essential oil were phytol (42.15%), squalene (16.81%), what's more pentadecanal (6.17%), pentadecanoic acid (4.49%), 3, 7, 11, 15-tetramethyl-2-hexadecen-1-ol (3.83%), phytone (2.05%) and the other 74 chemical compositions were firstly identified from the essential oil of Pandanus amaryllifolius leaves. CONCLUSION: The chemical compositions of Pandanu samaryllifolius leaves essential oil was systematically, deeply isolated and identified for the first time. This experiment has provided scientific foundation for further utilization of Pandanus amaryllifolius leaves.

[Comprehensive therapeutic protocol of electroacupuncture combined with Chinese herbs and rehabilitation training for treatment of cerebral infarction: a multi-center randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of comprehensive therapeutic protocol of electroacupuncture combined with active-blood-and-dissolve-stasis herbs and rehabilitation training for cerebral infarction. METHODS: A multi-center randomized controlled trial was done, three hundred and twenty cases were divided into four groups: electroacupuncture combined with active-blood and dissolve-stasis herbs and rehabilitation training group (group A), electroacupuncture combined with rehabilitation training group (group B), herbs combined with rehabilitation training group (group C) and rehabilitation training group (group D), 80 cases in each group. The following two groups of acupoints were used alternatively in electroacupuncture treatment: the first group including Vasomotor Area, Jianyu (LI 15), Biguan (ST 31), Hegu (LI 4) and Taichong (LR 3); the second group including Motor Area, Quchi (LI 11), Yanglingquan (GB 34) and Shenshu (BL 23). 20 mL Xiangdan injection and 250 mL 5% glucose injection or 250 mL 0.9% sodium chloride injection were used by intravenous drip in herbs treatment once a day. The rehabilitation training was performed by the professional physical therapist. Each group was treated with corresponding treatment protocol. The therapeutic effect was evaluated by index of the mortality or disability rate 3 months after the onset of disease. The intention to treat analysis (ITT) was used in data. RESULTS: The mortality or handicap rate 3 months after the onset of disease of four groups were 17.5% (14/80) in group A, 22.5% (18/80) in group B, 40. 0% (32/80) in group C, and 31.3% (25/80) in group D, respectively. The group A has a best therapeutic effect (vs group C, group D, both P<0.05), and there was no adverse event. CONCLUSION: The combined application of electroacupuncture, active-blood and dissolve-stasis herbs and rehabilitation training is a better treatment for cerebral infarction in clinic.