Protein-coated cobalt oxide-hydroxide nanospheres deliver photosensitizer IR780 iodide for near-infrared light-triggered photodynamic/photothermal/chemodynamic therapy against colon cancer.

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.

A multifunctional nanotheranostic agent based on Lenvatinib for multimodal synergistic hepatocellular carcinoma therapy with remarkably enhanced efficacy.

Lenvatinib (LT), a first-line molecular targeted therapeutic drug for hepatocellular carcinoma (HCC), has been replacing the status of Sorafenib (SF) as the clinically preferred and irreplaceable treatment for a decade. To overcome the low drug utilization and limited single efficacy of LT, ultrasmall copper sulfide nanocrystals (Cu2-xS NCs), and ultrasmall gold nanoparticle (AuNPs) were evenly wrapped into galactosamine conjugated poly(lactide-co-glycolide) (PLGA) as the drug delivery nanoparticles (CAL@PG) by nanoprecipitation. The CAL@PG NPs exhibited excellent stability under physiological conditions, whereas they released LT rapidly in the unique tumor microenvironment (TME) and high temperature, which could be provided by the near-infrared-II (NIR-II) photothermal effect of Cu2-xS NCs. Moreover, the temperature elevation, regenerated hydrogen peroxide (H2O2), and lower pH of TME could substantially boost the reaction potency of copper Fenton-like chemistry. More importantly, this combined therapy significantly improved the efficacy of LT, provided a multifunctional LT delivery system, and enriched the nanoparticle-augmented multimodal synergistic HCC therapy modality.

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p-PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn.

Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

[GAO Hong's clinical experience in treatment of tic disorder with acupuncture technique of cultivating the primary and regulating the mind].

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.

Efficacy of Platelet-Rich Plasma in the Treatment of Fractures: A Meta-Analysis.

Background: Although numerous studies have reported the effectiveness of platelet-rich plasma (PRP) in promoting and enhancing bone healing, many orthopedic physicians remain skeptical of platelet-rich plasma in the treatment of fractures. The objective of this meta-analysis was to assess the efficacy of PRP in the treatment of fractures. Methods: We search for research on PRP treatment of fractures in Pubmed, Embase, Medline, and Cochrane libraries. Two independent reviewers assessed included studies and met to develop a consensus on included studies. We also assessed the risk of bias using Review Manager 5.3 software. Results: The present meta-analysis included 10 randomized controlled trials (RCT) containing 652 patients. In the fixed-effect meta-analysis of 10 RCTs, 8 RCTs found that fracture patients benefited from PRP treatment. The use of PRP reduced the time of fracture healing in 4 RCTs. Three RCTs found that PRP adjuvant therapy enhanced bone mineral density in the fracture trace and reduced the time of bone regeneration in mandibular fractures patients (standardized mean difference (SMD) = -1.99, 95%confidence interval (CI) = -2.64--1.35). And 3 RCTs found that PRP adjuvant therapy decreased the risk of revision surgery in fracture patients (SMD = 1.83, 95%CI = 1.10-3.04). Conclusion: PRP adjuvant therapy is beneficial for the treatment of fracture patients, particularly those with mandibular fractures, and decreased the risk of revision surgery in fracture patients.

Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.

Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.

Effects of Curcuma longa L., Eucommia ulmoides Oliv. and Gynostemma pentaphyllum (Thunb.) Makino on Cytokine Production in Stimulated Peripheral Blood Mononuclear Cells in Patients with Tuberculosis.

BACKGROUND: Tuberculosis (TB) infection triggers the innate and adaptive immune responses. Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L. extracts exhibit various immunomodulatory effects. OBJECTIVE: This study aimed to determine the effects of 3 extracts used in Traditional Chinese Medicine (TCM) on cytokine production in peripheral blood mononuclear cells (PBMCs) obtained from patients with TB. DESIGN: The research team performed an in vitro study with self controls. SETTING: The study took place at the Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taiwan. PARTICIPANTS: 18 patients diagnosed with pulmonary TB were enrolled in the study. INTERVENTION: Purified protein derivative (PPD)-stimulated PBMCs were cultured for 48 h in the presence and absence of 0.05 or 0.1 mg/mL of herbal extracts. OUTCOME MEASURES: Cytokine levels of interferon (IFN)-γ, interleukin (IL)-10, IL-12, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 in the culture supernatant were measured. RESULTS: C longa L., E ulmoides Oliv. and G pentaphyllum (Thunb.) Makino extracts decreased IFN-γ production in PPD-stimulated PBMCs. C longa L. extract did not exhibit a marked and consistent effect on the production of IL-10, IL-12, TNF-α and TGF-ß1. E ulmoides Oliv. extract increased the production of IL-10, TNF-α and TGF-ß1. G pentaphyllum (Thunb.) Makino extract increased the production of IL-10, IL-12, TNF-α and TGF-ß1. CONCLUSION: These results show that G pentaphyllum (Thunb.) Makino might enhance cell immunity since it increased the production of IL-12 and TNF-α with dose effect.

[Discussion of optimization of sham acupuncture setting based on a clinical trial about acupuncture treatment of migraine published in British Medical Journal].

In the randomized controlled clinical trials of acupuncture, the setting of the control group (sham acupuncture) directly affected the interpretations about their outcomes (beyond placebo), and has been being the hot spot and difficult problem. In the present paper, we discussed various types of sham acupuncture (invade and non-invade needling) commonly used nowadays and made an in-depth analysis on the factors contributing to the successful blinding to patients with episodic migraine without aura in a clinical study published in British Medical Journal (2020, 368:m697). Moreover, we put forward some thoughts on how to optimize the setting of sham acupuncture in the treatment of pain diseases. These thoughts are 1) setting different placebo control group for different types of pain, 2) selecting conventional acupoints not associated with the disease, 3) selecting the most sui-table type of placebo acupuncture through pre-tests, 4) choosing the distal non-meridian and non-acupoint not in the same neuronal segment with the pain locus when using non-invade consolation needling, 5) trying best to reduce the patients' doubts about placebo acupuncture operation, 6) selecting subjects with little or without acupuncture experience for multicenter studies, and 7) trying best to select objective indicators and to avoid the subjects' report bias when evaluating the effects of acupuncture and consolation acupuncture.

[Clinical efficacy and safety of moxibustion as adjuvant therapy for COPD in stable phase: a Meta-analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [MD=-0.31, 95%CI:-0.49--0.13, P=0.0006]; ②the adjuvant therapy with moxibustion improved lung function significantly [FEV1% (MD=4.00, 95%CI:2.63-5.37, P<0.000 01) and FEV1/FVC (MD=3.56, 95%CI:1.69-5.43, P=0.000 2)]; ③the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) (MD=35.00, 95%CI:18.02-51.99, P<0.000 1); ④the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly (MD=-0.62, 95%CI:-1.18--0.05, P=0.03); ⑤no adverse reaction was reported in the included literature. CONCLUSION: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.

Tachykinin signaling inhibits task-specific behavioral responsiveness in honeybee workers.

Behavioral specialization is key to the success of social insects and leads to division of labor among colony members. Response thresholds to task-specific stimuli are thought to proximally regulate behavioral specialization, but their neurobiological regulation is complex and not well understood. Here, we show that response thresholds to task-relevant stimuli correspond to the specialization of three behavioral phenotypes of honeybee workers in the well-studied and important Apis mellifera and Apis cerana. Quantitative neuropeptidome comparisons suggest two tachykinin-related peptides (TRP2 and TRP3) as candidates for the modification of these response thresholds. Based on our characterization of their receptor binding and downstream signaling, we confirm a functional role of tachykinin signaling in regulating specific responsiveness of honeybee workers: TRP2 injection and RNAi-mediated downregulation cause consistent, opposite effects on responsiveness to task-specific stimuli of each behaviorally specialized phenotype but not to stimuli that are unrelated to their tasks. Thus, our study demonstrates that TRP signaling regulates the degree of task-specific responsiveness of specialized honeybee workers and may control the context specificity of behavior in animals more generally.

Neuroprotective effects of Ginkgolide B in focal cerebral ischemia through selective activation of prostaglandin E2 receptor EP4 and the downstream transactivation of epidermal growth factor receptor.

The present study was undertaken to identify whether prostaglandin E2 receptor is the potential receptor/binding site for Ginkgolide A, Ginkgolide B, Ginkgolide K, and Bilobalide, the four main ingredients of the Ginkgo biloba L., leaves. Using functional assays, we identified EP4, coupled with Gs protein, as a target of Ginkgolide B. In human neuroblastoma SH-SY5Y cells suffered from oxygen-glucose deprivation/reperfusion, Ginkgolide B-activated PKA, Akt, and ERK1/2 as well as Src-mediated transactivation of epidermal growth factor receptor. These resulted in downstream signaling pathways, which enhanced cell survival and inhibited apoptosis. Knockdown of EP4 prevented Ginkgolide B-mediated Src, epidermal growth factor receptor (EGFR), Akt, and ERK1/2 phosphorylation and neuroprotective effects. Moreover, Src inhibitor prevented Ginkgolide B-mediated EGFR transactivation and the downstream Akt and ERK1/2 activation, while the phosphorylation of PKA induced by Ginkgolide B was not affected, indicating Ginkgolide B might transactivate EGFR in a ligand-independent manner. EP4 knockdown in a rat middle cerebral artery occlusion (MCAO) model prevented Ginkgolide B-mediated infarct size reduction and neurological assessment improvement. At the same time, the increased expressions of p-Akt, p-ERK1/2, p-PKA, p-Src, and p-EGFR and the deceased expression of cleaved capases-3 induced by Ginkgolide B in cerebral cortex were blocked due to EP4 knockdown. In conclusion, Ginkgolide B exerts neuroprotective effects in rat MCAO model through the activation of EP4 and the downstream transactivation of EGFR.

[Chinese medicine master SHENG Xie-sun's creative viewpoint on acupuncture-moxibustion and acupoints of Zhejiang school].

The creative viewpoint of SHENG Xie-sun, the master of Zhejiang school of Chinese medicine is introduced regarding the theories of acupuncture-moxibustion and acupoints. It is stated by master SHENG that the five-tissue needling methods are applicable not only for physical disorders, but also for zangfu disorders. Of these methods, the nearby bone needling method presents an instructive significance in treatment of pain disorder. The "reinforcing in the upper and reducing in the lower" needling method supplements the reinforcing and reducing theory of acupuncture. Master SHENG has put forward the theory of flexible selection of acupoint, the phenomenon of acupoint groups and the application of transverse acupoint composition, as well as the measures for intensifying needling induction, promoting qi regulation of acupuncture and improving clinical effect. Besides, the seven Chinese characters are used to summarize acupoint composition, meaning "main point, supplementary point, nearby point, corresponding point, back-shu point, front-mu point and extra point" separately. This creative viewpoint provides a clearer and more feasible mode in treatment with acupuncture-moxibustion and is instructive proactively in clinical practice.

[Herb-separated moxibustion on dysmenorrhea in ovarian endometriosis: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect of herb-separated moxibustion on dysmenorrhea in ovarian endometriosis. METHODS: A total of 54 patients with ovarian endometriosis dysmenorrhea were randomized into a herb-separated moxibustion group and a waiting-list group, 27 cases in each one (3 cases dropped off in the herb-separated moxibustion group, 4 cases dropped off in the waiting-list group). Herb-separated moxibustion was applied at hypogastrium and lumbosacral area for 30 min in the herb-separated moxibustion group, once a week for 3 months, and oral ibuprofen sustained-release capsule was given to relieve pain when necessary. Excepting giving ibuprofen sustained-release capsule when necessary, no more intervention was adopted in the waiting-list group. Before and after treatment and in 3 months follow-up, visual analogue scale (VAS) score, days of dysmenorrhea, total dose of oral painkiller were observed. RESULTS: Compared before treatment, the VAS scores after tratment and in follow-up were decreased in the herb-separated moxibustion group (P<0.05), and were less than those in the waiting-list group (P<0.05); the days of dysmenorrhea and the total doses of oral painkiller after tratment and in follow-up were decreased in the herb-separated moxibustion group (P<0.05), and were less than those in the waiting-list group (P<0.05). CONCLUSION: Herb-separated moxibustion can effectively improve dysmenorrhea symptom and shorten dysmenorrhea days in patients with ovarian endometriosis.

[Clinical application and mechanism exploration on dysosmia treated with acupuncture and moxibustion].

Dysosmia affects not only odour identification, but also memory, appetite, immunity and affection. Moreover, it suggests the occurrence of some diseases. The etiology of dysosmia is various and the treatment with western medicine is limited. In this paper, by analyzing the relevant research articles on olfactory disorders treatment with acupuncture and moxibustion, the clinical application of acupuncture and moxibustion, the thought of its diagnosis and treatment as well as relevant effect mechanism were explored. It is anticipated to provide the clinical physicians with the references to the treatment of dysosmia.

Self-Sufficient and Highly Efficient Gold Sandwich Upconversion Nanocomposite Lasers for Stretchable and Bio-applications.

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

Proteome of thymus and spleen reveals that 10-hydroxydec-2-enoic acid could enhance immunity in mice.

Objectives: 10-hydroxydec-2-enoic acid (10-HDA), a unique component of royal jelly existing only in nature, has the potential to promote human health. Knowledge of 10-HDA in regulating immuno-activity, however, is lacking. The aim of our work is to gain a novel understanding of 10-HDA in promoting immunity.Methods: Immuno-suppressed mice were generated by cyclophosphamide injection, After 10-HDA supplementation to the mice to rescue their immunity, the proteomes of the thymus and spleen were analyzed.Results: The weight of the body, thymus, and spleen in cyclophosphamide-induced mice recovered by 10-HDA indicate its potential role in immuno-organ protection. In the thymus, the enhanced activity of pathways associated with DNA/RNA/protein activities may be critical for T-lymphocyte proliferation/differentiation, and cytotoxicity. In the spleen, the induced pathways involved in DNA/RNA/protein activities, and cell proliferative stimulation suggest their vital role in B-lymphocyte affinity maturation, antigen presentation, and macrophage activity. The up-regulated proteins highly connected in networks modulated by 10-HDA indicate that the mice may evolve tactics to respond to immuno-organ impairment by activating critical physiological processes.Conclusion: Our data constitute a proof-of-concept that 10-HDA is a potential agent to improve immunity in the thymus and spleen and offer a new venue for applying natural products to the therapy for hypoimmunity.

[Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review].

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.

Should acupuncture, biofeedback, massage, Qi gong, relaxation therapy, device-guided breathing, yoga and tai chi be used to reduce blood pressure?: Recommendations based on high-quality systematic reviews.

BACKGROUND: This review aims to rate the quality of evidence and the strength of recommendations in high-quality systematic reviews of non-drug therapies. Hypertensive patients who are resistant or non-adherent to antihypertensive drugs may be easier to manage if they choose alternative non-drug therapies for hypertension, based on this review. METHODS: P: Adults (>18 years), except pregnant women, with essential hypertension. I: Cupping, moxibustion, acupuncture, acupoint stimulation, yoga, meditation, tai chi, Qi gong, Chinese massage, massage, spinal manipulation, biofeedback, device-guided breathing therapy, aromatherapy, music therapy, and relaxation approaches. C: 1. No treatment. 2. Sham therapy. 3. Conventional treatment, including antihypertensive drugs and lifestyle modification (e.g., exercise). O: 1. Change in the incidence of cardiovascular death. 2. Change in the incidence of myocardial infarction. 3. Change in the incidence of stroke. 4. Change in blood pressure (BP). 5. Efficacy rate of BP lowering. 6. Adverse effects (review specific). S: Systematic reviews of randomized controlled trials, including meta-analyses and assessments of the methodological quality/risk of bias. INFORMATION SOURCES: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane library, PubMed, Web of Science, China National Knowledge Infrastructure, and Chinese Scientific Journal Database were searched. The bibliographies of the included articles were also searched for relevant systematic reviews. GRADE criteria were used to rate the quality of evidence in systematic reviews considering 6 factors, including risk of bias. RESULTS: This review ultimately included 13 systematic reviews of 14 non-drug therapies (acupuncture, wet cupping, Baduanjin, blood letting, auricular acupuncture, music, massage, Qi gong, moxibustion, relaxation therapies, biofeedback, device-guided breathing, yoga and tai chi) based on the inclusion criteria. The quality of evidence was generally low, and weak recommendations were given for most therapies except massage and acupuncture plus antihypertensive drug. Based on the analyzed evidence, massage and acupuncture plus antihypertensive drug could benefit people who want to lower their BP and do not have contraindications for massage and acupuncture plus antihypertensive drug. DISCUSSION/STRENGTH: The GRADE approach makes this review a unique reference for people who are considering the grade of quality of evidence in systematic reviews, the balance of desirable and undesirable consequences and the strength of recommendations to decide which intervention should be used to reduce BP. LIMITATIONS: Many non-drug therapies were excluded due to the low methodological quality of their systematic reviews, and only 14 therapies were evaluated in this review. As no patient-important outcomes were reviewed, surrogate outcomes were used to rate the strength of recommendations. This approach may cause a decrease in evidence quality according to GRADE, but we argue that this is appropriate in the context of this review.

Xanthone-derived polyketides from the Thai mangrove endophytic fungus Phomopsis sp. xy21.

Six new xanthone-derived polyketides, named phomoxanthones F-K (1-6), along with three known ones, were isolated from Phomopsis sp. xy21, which was isolated as an endophytic fungus from the Thai mangrove Xylocarpus granatum. Phomoxanthone F (1) represents the first xanthone-derived polyketide containing a 10a-decarboxylated benzopyranone nucleus that was substituted by a 4-methyldihydrofuran-2(3H)-one moiety at C10a. Phomoxanthones G (2) and H (3) are highly oxidized xanthone-derived polyketides containing a novel 5-methyl-6-oxabicyclo[3.2.1]octane motif. This is the first report of a C6-O-C12 bridge in xanthone-derived polyketides. Additionally, a plausible biogenetic pathway for these xanthone-derived polyketides is proposed.