Chemical components characterization and in vivo metabolites profiling of Lingbao Huxin Dan by gas chromatography-mass spectrometry and ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry.

Lingbao Huxin Dan (LBHX) is an effective prescription for treating various cardiovascular diseases. However, its systematic chemical composition analysis and important marker components remain unclear, which hinders the development of standards or guidelines for quality evaluation. Herein, a high-resolution and efficient method was established to comprehensively investigate the chemical ingredients and metabolites of LBHX by using gas chromatography-tandem mass spectrometry and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AutoDock Vina was applied to conduct visual screening for identifying potential active compounds targeting two important sick sinus syndrome-associated proteins. As a result, 53 volatile compounds, as well as 191 non-volatile chemical components, including bufadienolides, diterpenoids, bile acids, phenolic acids, and triterpenoid saponins, were unambiguously characterized or tentatively identified. Fifty prototypes and 62 metabolites were identified in the plasma of rats, whilst metabolism reactions included phase I reactions (hydrolysis, oxidation, and hydroxylation) and phase II reactions (glucuronidation and methylation). Eleven compounds with good binding affinity have been observed by docking with key proteins. It is the first systematic study on the pharmacodynamic material basis of LBHX and the result consolidates the foundation for further study regarding the mechanism in treating cardiovascular diseases.

Using AGREE II reporting checklist to evaluate the quality of Tuina clinical practice guidelines.

Objective: The objective of this study is to evaluate the methodological quality of Tuina clinical practice guidelines (CPGs). Methods: Computer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines. Results: A total of eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as "highly recommended." The worst guideline had a final score of 241 and was rated as "not recommended." Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended. Conclusion: The number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted clinical practice guideline development and reporting norms. In the future, reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, should be emphasized in the development of the Tuina guidelines. These initiatives could improve the quality and applicability of clinical practice guidelines to guide and standardize the clinical practice of Tuina.

Protective Effect of l-Theanine on Cyclophosphamide-Induced Testicular Toxicity in Mice.

l-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of l-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last l-theanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of l-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that l-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of l-theanine on CP-induced testicular toxicity. l-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.

Multi-omics and network pharmacology study reveals the effects of Dengzhan Shengmai capsule against neuroinflammatory injury and thrombosis induced by ischemic stroke.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan Shengmai capsule (DZSM) is a traditional herb medicine used by Dai, an ethnic-minority community living in Xishuang banna tropical rainforest in Southwest of China. It was originally intended to treat disorders caused by insufficient brain function, characterized by gibberish, unresponsiveness, or confusion. Accumulating clinical evidences exhibited that it is effective on treating ischemic stroke (IS). However, the action of DZSM against IS needs to be further elucidated. AIM OF THE STUDY: To investigate the effect of DZSM and its active components against IS and the way of its action by multi-omics and network pharmacology. MATERIALS AND METHODS: A middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to investigate the effect of DZSM on the focal cerebral ischemia/reperfusion injury. An integrated strategy combining metabolomics, network pharmacology and transcriptomics was performed to systematically clarify the underlying mechanism of action of DZSM against IS. AutoDock Vina was applied to conduct molecular docking simulation for the binding between the potential active compounds and targets. Arachidonic acid (AA) induced platelet aggregation and lipopolysaccharide (LPS) stimulated microglial cells BV2 inflammation models were applied for the in vitro validation of effects of DZSM and its potential active compounds. RESULTS: In MCAO/R rats, DZSM could significantly reduce the infarct volume. Putative target prediction and functional enrichment analysis based on network pharmacological indicated that the key targets and the potential active compounds played important roles in DZSM's treatment to IS. The targets included four common genes (PTGS1, PTGS2, NFKB1 and NR1I2) and five key TFs (NFKB1, RELA, HIF1A, ESR1 and HDAC1), whilst 22 potential active compounds were identified. Molecular docking indicated that good binding affinity have been seen between those compounds and NR1I2, NFKB1, and RELA. Multi-omics study revealed that DZSM could regulate glutamate by influencing citrate cycle and glutamate involved pathways, and have showed neuroprotection activity and anti-inflammation activity by inhibiting NF-κB pathway. Neuroprotective effects of DZSM was validated by regulating of NF-κB signaling pathway and its downstream NO, TNF-α and IL-6 cytokines contributed to the activity of DZSM and its active compounds of scutellarin, quercetin 3-O-glucuronide, ginsenoside Rb1, schizandrol A and 3, 5-diCQA, whilst the antithrombotic activity of DZSM and its active compounds of schisanhenol, apigenin and schisantherin B were screened out by anti-platelet aggregation experiment. CONCLUSION: DZSM could against IS via regulating its downstream NO, TNF-α and IL-6 cytokines through NF-κB signaling pathway and alleviating thrombosis.

Functional groups on wheat (Triticum aestivum) root surface affect aluminium transverse accumulation.

Plant root growth is inhibited markedly by aluminium (Al) even at micromolar concentration and Al is mainly accumulated in plant roots outer layer cell walls. But the underlying reason for this asymmetric transverse distribution is unknown. In this study, two wheat (Triticum aestivum L.) genotypes ET8 and ES8 differing in Al resistance were investigated by hydroculture. The Al-tolerant ET8 expressed a higher root elongation rate (RER) than Al-sensitive ES8 under Al stress. Morphological examination showed symptoms such as root surface ruptures were observed in ET8 and ES8, with ES8 being more obvious. The cation exchange capacity (CEC) values of root tips of ES8 under different Al concentrations are higher than those of ET8. The sensitive genotype ES8 accumulated more Al than ET8 in plant apical root tips as well as cell walls. Under 48 h Al exposure, the root cell wall pectin concentration was increased with a higher magnitude in ES8 than in ET8. The functional groups on ET8 and ES8 roots outer layer and inner cells were investigated by Fourier transform infrared spectrometry (FTIR) under Al stress. The FTIR spectra of selected examined areas showed that the characteristic absorption peaks were located at 1692, 2920, and 3380 cm-1. The outer layer cells had stronger peaks than inner cells at wavenumber 1680-1740 cm-1, indicating root outer layer cells contain more carboxyls in both ET8 and ES8. The results demonstrate that Al transverse distribution on plants apical root cross section is likely influenced by functional groups such as negatively charged carboxylic acid.

Tuina combined with Adjuvant therapy for lumbar disc herniation: A network meta-analysis.

OBJECTIVE: To directly or indirectly compare the effectiveness and pain relief of TN combined with different treatments for lumbar disc herniation (LDH). METHODS: The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Biomedical Literature database (CBM), Chinese Scientific Journal Database (VIP), PubMed, Embase, Cochrane library, and Web of Science were searched from inception to July 2020. Only full texts of randomized controlled trials (RCTs) that make comparisons between Tuina and Tuina combined with other methods were included. We extracted trial data and assessed the risk of bias by two reviewers independently. We pooled continuous data in standard mean differences (SMDs) and binary data in risk ratios (RRs), and provided 95% confidence intervals. The primary outcomes were the effectiveness rate. The secondary outcome was pain measurements including visual analog scale (VAS) scores. RESULTS: Forty-four trials which included 4741 participants and 16 kinds of interventions were selected in our study. Tuina combined with Acupuncture was the most frequently investigated intervention. Five (31%) kindnesces (SMDs) and binary data in risk ratios (RRs), and provided 95% confidence intervals. The primary outcomes were the effectiveness rate. The secondary outcome was pain measurements including visual analog scale (VAS) scores. RESULTS: Forty-four trials of treatments among 15 increased the healing rate more significantly compared with Tuina(TN), including Tuian combined with Traction and formula(TN + TRA + FM), Tuina combined with formula(TN + FM), Tuina combined with Traction and Acupuncture(ACU + TN + TRA), Tuian combined with Traction(TN + TRA), Tuina combined with Electroacupuncture(EA + TN), Tuina combined with the warm needle(TN + WN), Tuina combined with Acupuncture(ACU + TN). Seven treatments including Tuina combined with Electroacupuncture(EA + TN), Tuian combined with Traction and formula(TN + TRA + FM), Tuina combined with Acupuncture(ACU + TN), Tuina combined with formula(TN + FM), Acupuncture(ACU), Tuian combined with Traction(TN + TRA), Tuina combined with the warm needle(TN + WN) had better effects in reducing pain intensity compared with Tuina, range from 0.01 (95%Crl 0-0.08) for EA + TN to 0.30 (95%Crl 0.20-0.45) for TN + WN. CONCLUSIONS: According to the comprehensive review, Tuina combined with Traction and formula(TN + TRA + FM) seemed to be the most recommendable treatment which is more affordable and effective. However, all the available evidence was of low quality, so more high-quality studies are expected to confirm the effectiveness. REGISTRATION NUMBER: PROSPERO CRD42020193068.

Silencing PEX26 as an unconventional mode to kill drug-resistant cancer cells and forestall drug resistance.

Promoting the macroautophagy/autophagy-mediated degradation of specific proteins and organelles can potentially be utilized to induce apoptosis in cancer cells or sensitize tumor cells to therapy. To examine this concept, we enriched for autophagosomes from histone deacetylase inhibitor (HDACi)-sensitive U937 lymphoma cells and isogenic HDACi-resistant cells. Mass spectrometry on autophagosome-enriched fractions revealed that HDACi-resistant cells undergo elevated pexophagy, or autophagy of the peroxisome, an organelle that supports tumor growth. To disturb peroxisome homeostasis, we enhanced pexophagy in HDACi-resistant cells via genetic silencing of peroxisome exportomer complex components (PEX1, PEX6, or PEX26). This consequently sensitized resistant cells to HDACi-mediated apoptosis, which was rescued by inhibiting ATM/ataxia-telangiectasia mutated (ATM serine/threonine kinase), a mediator of pexophagy. We subsequently engineered melanoma cells to stably repress PEX26 using CRISPR interference (CRISPRi). Melanoma cells with repressed PEX26 expression showed evidence of both increased pexophagy and peroxisomal matrix protein import defects versus single guide scrambled (sgSCR) controls. In vivo studies showed that sgPEX26 melanoma xenografts recurred less compared to sgSCR xenografts, following the development of resistance to mitogen-activated protein kinase (MAPK)-targeted therapy. Finally, prognostic analysis of publicly available datasets showed that low expression levels of PEX26, PEX6 and MTOR, were significantly associated with prolonged patient survival in lymphoma, lung cancer and melanoma cohorts. Our work highlighted that drugs designed to disrupt peroxisome homeostasis may serve as unconventional therapies to combat therapy resistance in cancer.Abbreviations: ABCD3/PMP70: ATP binding cassette subfamily D member 3; ACOX1: acyl-CoA oxidase 1; AP: autophagosome; COX: cytochrome c oxidase; CQ: chloroquine; CRISPRi: clustered regularly interspaced short palindromic repeats interference; DLBCL: diffuse large B-cell lymphoma; GO: gene ontology; dCas9: Cas9 endonuclease dead, or dead Cas9; HDACi: histone deacetylase inhibitors; IHC: Immunohistochemistry; LAMP2: lysosomal associated membrane protein 2; LCFAs: long-chain fatty acids; LFQ-MS: label-free quantitation mass spectrometry; LPC: lysophoshatidylcholine; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PBD: peroxisome biogenesis disorders; PTS1: peroxisomal targeting signal 1; ROS: reactive oxygen species; sgRNA: single guide RNA; VLCFAs: very-long chain fatty acids; Vor: vorinostat; WO: wash-off.

Bacteria-Mediated Tumor Therapy via Photothermally-Programmed Cytolysin A Expression.

By leveraging the ability of bacteria to express therapeutic protein cytolysin A (ClyA) through plasmid transformation, a thermally-activated biohybrid (TAB@Au) is constructed by biomineralizing gold nanoparticles (AuNPs) on the E. coli surface. Due to the feature of anaerobic bacteria homing to tumor microenvironments, the bacteria-based antitumor vehicles can be efficaciously accumulated at tumor sites. Under NIR laser irradiation, the biomineralized AuNPs harvest transdermal photons and convert them into local heat for photothermal therapy. After that, the produced heat elicits the expression of ClyA for killing tumor cells. In vitro and in vivo experiments verify the conception that the current therapeutic modality greatly inhibits the proliferation of tumor cells. In terms of the spatial specificity and non-invasiveness of NIR laser, the bacteria-based phototherapy represents an appealing way for tumor therapy.

NIR-activated self-sensitized polymeric micelles for enhanced cancer chemo-photothermal therapy.

NIR-activated therapies based on light-responsive drug delivery systems are emerging as a remote-controlled method for cancer precise therapy. In this work, fluorescent dye indocyanine green (ICG)-conjugated and bioactive compound gambogic acid (GA)-loaded polymeric micelles (GA@PEG-TK-ICG PMs) were smoothly fabricated via the self-assembly of the reactive oxygen species (ROS)-responsive thioketal (TK)-linked amphiphilic polymer poly(ethyleneglycol)-thioketal-(indocyanine green) (PEG-TK-ICG). The resultant micelles demonstrated increased resistance to photobleaching, enhanced photothermal conversion efficiency, NIR-controlled drug release behavior, preferable biocompatibility, and excellent tumor accumulation performance. Moreover, upon an 808 nm laser irradiation, the micellar photoactive chromophore ICG converted the absorbed optical energy to both hyperthermia for photothermal therapy (PTT) and ROS as the feedback trigger to the micelles for the tumor-specific release of GA, which could serve as not only a chemotherapeutic drug to directly kill tumor cells but also a heat shock protein 90 (HSP90) inhibitor to realize the photothermal sensitization. As a result, an extremely high tumor inhibition rate (97.9%) of mouse 4 T1 breast cancer models was achieved with negligible side effects after the chemo-photothermal synergistic therapy. This NIR-activated nanosystem with photothermal self-sensitization function may provide a feasible option for the effective treatment of aggressive breast cancers.

Multifunctional Hybrid Hydrogel Enhanced Antitumor Therapy through Multiple Destroying DNA Functions by a Triple-Combination Synergistic Therapy.

Brachytherapy, as an effective setting for precise cancer therapy in clinic, can lead to serious DNA damage. However, its therapeutic efficacy is always limited by the DNA self-repair property, tumor hypoxia-associated radiation resistance as well as inhomogeneous distribution of the radioactive material. Herein, a multifunctional hybrid hydrogel (131 I-hydrogel/DOX/GNPs aggregates) is developed by loading gold nanoparticle aggregates (GNPs aggregates) and DOX into a radionuclide iodine-131 (131 I) labelled polymeric hydrogels (131 I-PEG-P(Tyr)8 ) for tumor destruction by completely damaging DNA self-repair functions. This hybrid hydrogel exhibits excellent photothermal/radiolabel stability, biocompatibility, and fluorescence/photothermal /SPECT imaging properties. After local injection, the sustained releasing DOX within tumor greatly inhibits the DNA replication. Meanwhile, GNPs aggregates as a radiosensitizer and photosensitizer show a significant improvement of brachytherapeutic efficacy and cause serious DNA damage. Simultaneously, GNPs aggregates induce mild photothermal therapy under 808 nm laser irradiation, which not only inhibits self-repair of the damaged DNA but also effectively relieves tumor hypoxic condition to enhance the therapeutic effects of brachytherapy, leading to a triple-synergistic destruction of DNA functions. Therefore, this study provides a highly efficient tumor synergistic therapy platform and insight into the synergistic antitumor mechanism in DNA level.

Acupuncture for diabetic peripheral neuropathy: An overview of systematic reviews.

BACKGROUND: Acupuncture has been widely used to treat diabetic peripheral neuropathy (DPN) in China as a complementary and alternative therapy. This study aims to summarize the characteristics and evaluate the methodology quality of the systematic reviews (SRs) regarding acupuncture for DPN. METHODS: A comprehensive literature search was performed from inception to February 2020. We assessed the methodological quality of the included SRs with the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool, adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to evaluate the reporting characteristics of included SRs, and utilized the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of evidence for outcomes including total effective rate, sensory nerve conduction velocity, motor nerve conduction velocity and adverse events. One-way analysis of variance and multiple linear regression were conducted to evaluate the associations between characteristics and two index scores (PRISMA and AMSTAR 2). RESULTS: Eighteen SRs were included in this overview. The methodology quality of the included SRs ranged from very low to high. Only protocol registration and funding source reported were associated with the AMSTAR 2 index scores, while no variable showed significant difference in the PRISMA scores. The overall quality of evidence in included SRs ranged from "very low" to "moderate". CONCLUSION: This overview suggested beneficial effects of acupuncture on DPN, whereas the results should be interpreted with cautious owing to methodology flaws, providing reference for further improvement of the study design.

The effectiveness and safety of Tuina for tension-type headache: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Tension-type headache (TTH) is one of the most common primary headache diseases in the world and has a serious negative impact on the physical and mental health of patients. Tuina is now widely used to treat tension-type headaches. This article aims to systematically review the evidence about the effectiveness of Tuina on the effectiveness rate, pain intensity, and impact of headache in individuals with TTH. METHODS: Eight databases for randomized controlled trials (RCTs) of Tuina were included in treatments for TTH. Cochrane Collaboration's tool was applied to evaluate the quality of the studies. Confidence in the effect estimates was determined with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. We use the software STATA 12.0 for meta-analysis and TSA software for test sequence analysis. RESULTS: Seven studies were included with a total sample of 1228 individuals. Meta-analysis results showed that Tuina was superior to drugs for improving the effectiveness rate (RR = 1.49, 95%CI: 1.25 to 1.77, p < 0.01, low evidence). A visual analog scale (VAS) score of Tuina was significantly lower than that of drugs (WMD = -0.738, 95% CI: -1.128 to -0.349, p < 0.01, moderate evidence). The trial sequential analysis showed that the effectiveness of Tuina for TTH was accurate. Adverse events were tolerable. CONCLUSION: Tuina has a certain effect in treating tension headache. However, due to the low level of methodological quality included in the article, this conclusion should be considered cautiously. More studies are necessary to strengthen the evidence regarding the effectiveness and safety of Tuina for subjects with TTH.

Clinical Efficacy and Safety of Acupressure on Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effectiveness and safety of acupressure on low back pain (LBP). METHODS: We searched 7 electronic databases and 2 trial registries through December 28, 2020. Randomized controlled trials (RCTs) of acupressure on LBP were considered for meta-analysis with Revman 5.3 and Stata 15.0 software. Methodological quality was evaluated using the Cochrane Collaboration's tool. Trial sequential analysis (TSA) was used to quantify the statistical reliability. HETRED analysis and GRADE were used to determine the heterogeneity and quality of the results, respectively. RESULTS: Twenty-three RCTs representing 2400 participants were included. Acupressure was superior to tuina massage on response rate (RR 1.25; 95% CI, 1.16 to 1.35; P < 0.00001) and in the standardized mean difference (SMD) for pain reduction [SMD -1.92; 95% CI, -3.09 to -0.76; P=0.001]. Likewise, acupressure was superior to physical therapy [SMD, -0.88; 95% CI, -1.10 to -0.65; P < 0.00001] and to usual care [SMD, -0.32; 95% CI, -0.61 to -0.02; P=0.04] in pain reduction. The Oswestry Disability Index was significantly improved by acupressure compared with usual care [SMD, -0.55; 95% CI, -0.84 to -0.25; P=0.0003]. The combination of acupressure with either manual acupuncture or electro-acupuncture showed significant improvements over the adjuvant therapies alone in response rate [RR 1.19; 95% CI, 1.13 to 1.26; P < 0.00001], pain reduction, and the Japanese Orthopedic Association score (JOA). However, each study displayed substantial heterogeneity. Through subgroup sensitivity analysis and -HETRED analysis, the heterogeneity of acupressure compared with manual acupuncture decreased while the results maintained significance with respect to pain reduction [SMD -0.9; 95% CI, -1.21 to -0.6; P < 0.00001] and JOA [SMD, 0.66; 95% CI, 0.33 to 0.98; P < 0.00001]. Similar results were obtained comparing acupressure with electro-acupuncture with respect to pain [SMD, -1.07; 95% CI, -1.33 to -0.81; P < 0.00001] and JOA [SMD, 0.89; 95% CI, 0.51 to 1.27, P < 0.00001]. TSA demonstrated the effectiveness of acupressure as a standalone or as a combinative treatment (with manual acupuncture or electro-acupuncture) for LBP. CONCLUSION: Acupressure is an effective treatment for LBP. However, GRADE assessments downgraded the evidence in the trials, indicating that additional investigations are needed to confirm these observations.

Evaluating the Characteristics, Reporting and Methodological Quality of Systematic Reviews of Acupuncture for Low Back Pain by Using the Veritas Plot.

OBJECTIVE: To evaluate systematic reviews (SRs) of acupuncture for low back pain (LBP) in terms of characteristics, reporting and methodological quality using a Veritas plot and to explore factors that may be associated with methodological quality and reporting quality. STUDY DESIGN AND SETTING: We searched 8 electronic bibliographic databases to find all SRs, and we evaluated the SRs' quality in 6 dimensions, including publication year, design type, homogeneity, risk of publication bias, methodological quality by Assessment of Multiple Systematic Reviews (AMSTAR) 2 and reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Excel 2010 and Adobe Illustrator CC were used to draw and optimize Veritas plots. Exploratory analysis was done using SPSS software version 23.0 to explore factors related to AMSTAR-2 and PRISMA scores. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence quality evaluation tool was used to grade all the outcome indicators in the included literature. RESULTS: We included 19 SRs in the analysis. Literature quality rank scores ranged from 9.67 to 17.00, with an average score of 13.18 ± 2.35. The average score of AMSTAR-2 was 7.47, and the average score of PRISMA was 18.47. Overall, the main issues were research strategies, inclusion and exclusion criteria, publication bias, and registration in PROSPERO. The results of exploratory analysis showed that duplication of literature selected and appropriate tools to assess the risk of bias were related to the AMSTAR-2 score, and the summary of evidence was related to the PRISMA score. The GRADE quality evaluation results showed mainly low quality. CONCLUSION: The quality of SRs on acupuncture for low back pain should be improved, mainly by strengthening the methodological quality and reporting quality. The Veritas plot is an effective graphical evaluation method that is worth popularizing.

Tuina for cervical vertigo: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Cervical vertigo (CV), one of the most common causes of vertigo, makes patients feel dizzy, which seriously affects patients' lives. As a traditional Chinese bone-setting manipulation, Tuina is widely used to treat CV. This article aims to evaluate the effectiveness and safety of Tuina for CV. METHODS: Nine databases were searched. Methodological quality was evaluated with the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to determine confidence in the effect estimates. Stata 12.0 software was used to carry out the meta-analysis, and a trial sequential analysis (TSA) was performed with TSA 0.9. RESULTS: Nine randomized controlled trials (RCTs) were included. Low-quality evidence suggested that Tuina showed a significantly higher effectiveness rate compared to massage therapy (risk ratio (RR) = 1.11, 95% confidence intervals (CI): 1.05 to 1.17, p < 0.0001) and cervical traction (RR = 1.37, 95% CI: 1.09 to 1.72, p = 0.007; I2 = 0%, p = 0.826). Two trials reported that Tuina was better than acupuncture (RR = 1.40, 95% CI: 1.07 to 1.83) or betahistine mesilate (RR = 1.17, 95% CI: 0.99 to 1.37) based on an improved effectiveness rate. Low-quality evidence showed that Tuina was superior to massage therapy in improving scores on the evaluation scale for cervical vertigo (ESCV) (weighted mean differences (WMD) = 2.52, 95% CI: 1.11 to 3.94, p < 0.0001). Adverse events were tolerable. TSA revealed that an improved effectiveness rate was indicated. CONCLUSION: Tuina might improve the effectiveness rate and ESCV scores in patients with CV. However, the level of all the available evidence was low, and larger-scale and well-designed RCTs should be encouraged.

[Effect of electroacupuncture on diaphragmatic function in patients with post-stroke tracheotomy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on diaphragmatic function based on conventional treatment in patients with post-stroke tracheotomy tube. METHODS: A total of 70 patients were randomized into an observation group (35 cases) and a control group (34 cases, 1 case dropped off). Internal medical basic treatment and breathing training were given in both groups. Besides, Xingnao Kaiqiao acupuncture was applied at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5) and Weizhong (BL 40) in the control group, the needles were sustained for 30 min. On the basis of treatment in the control group, EA was applied at Tianding (LI 17), Fengchi (GB 20) and Jiaji (EX-B 2, C3-C5 ) in the observation group, with continuous wave, 10-20 Hz, 30 min each time. The treatment was given once a day, 6 times a week for 4 weeks in both groups. Before and after treatment, the diaphragmatic motility was measured by SonoSite ultrasound system (M-Turbo) in the two groups. RESULTS: Compared before treatment, the diaphragmatic motility after treatment was increased in both groups (P<0.01), and the improvement in the observation group was superior to the control group (P<0.01). CONCLUSION: Electroacupuncture can promote the recovery of diaphragmatic function in patients with post-stroke tracheotomy tube.

ICG-Conjugated and 125 I-Labeled Polymeric Micelles with High Biosafety for Multimodality Imaging-Guided Photothermal Therapy of Tumors.

Noninvasive multimodality imaging-guided precision photothermal therapy (PTT) is proven to be an effective strategy for tumor theranostics by integrating diagnostics and therapeutics in one nanoplatform. In this study, indocyanine green (ICG)-conjugated and radionuclide iodine-125 (125 I)-labeled polymeric micelles (PEG-PTyr(125 I)-ICG PMs) are strategically prepared by the self-assembly of the ICG-decorated amphiphilic diblock polymer poly(ethylene glycol)-poly(l-tyrosine-125 I)-(indocyanine green) (PEG-PTyr(125 I)-ICG). The as-prepared polymeric micelles exhibit favorable biocompatibility, excellent size/photo/radiolabel stability, a high-photothermal conversion efficiency, a passive tumor-targeting ability, and a fluorescence (FL)/photoacoustic (PA)/single photon emission computed tomography (SPECT) imaging property. After tail intravenous injection, the polymeric micelles can efficiently accumulate at the tumor site and present comprehensive FL/PA/SPECT images with a high sensitivity, excellent spatial resolution, and unlimited tissue penetration under near-infrared (NIR) irradiation. Upon 808 nm laser irradiation, the subsequent precision PTT of tumors can be achieved with minimal cumulative side effects. Thus, this capable multifunctional nanoplatform with simple components and preparation procedures for FL/PA/SPECT multimodality imaging-guided PTT can be a potential candidate for clinical tumor theranostics.

The Effectiveness and Safety of Acupoint Catgut Embedding for the Treatment of Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effectiveness and safety of acupoint catgut embedding therapy (ACET) in postmenopausal osteoporosis (PMOP). METHODS: Review of some databases from their inception to June 2018 and randomized controlled trials (RCTs) in which ACET with PMOP were included. Two researchers extracted and evaluated the information independently. Cochrane Collaboration's tool and Jadad scale were used to evaluate the quality of the studies. RevMan V.5.3.3 software was used to carry out the meta-analysis while trial sequential analysis (TSA) performed with TSA 0.9 software. RESULTS: 12 RCTs with 876 participants were included in this review. Meta-analysis showed that ACET alone was not superior to medication in effectiveness rate (RR= 1.11; 95% CI (0.89, 1.40); P=0.35) and E2 (SMD= 0.20; 95% CI (-0.17, 0.57); P=0.28; I 2 =20%) while ACET combining medication was more effective on the effectiveness rate (RR= 1.32; 95% CI (1.20, 1.46); P<0.000 01) and E2 (SMD= 1.24; 95% CI (0.63, 1.84); P<0.0001). Additionally, ACET combining calcium could increase the bone mineral density (BMD) of the L2~4 vertebrae and femur-neck [WMDL2~4 = 0.03; 95% CI (0.01, 0.05); P=0.003; and WMDFemur-neck = 0.07; 95% CI (0.03, 0.10); P = 0.0006], reduce TCM syndrome score [WMD = -1.85; 95% CI (-2.13, -1.57); P<0.000 01], improve patient's quality of life [WMDthree months = 6.90; 95% CI (3.90, 9.89); P<0.000 01; and WMDsix months = 12.34; 95% CI (5.09, 19.60); P=0.0009], and relieve pain [WMDVAS = -1.26; 95% CI (-1.66, -0.85); P<0.000 01; and WMDPain score = -2.59; 95% CI (-4.76, -0.43); P= 0.02]. The TSA showed that the effectiveness of ACET for PMOP was demonstrated accurately. CONCLUSIONS: ACET combining medication but not ACET alone is more effective than medication as comparison in the treatment of PMOP. As a novel treatment, ACET shows the potential of effectiveness and deserves further high quality of well-designed study.

[Effect of "Tongyuan" acupuncture treatment on success rate of extubation in stroke patients undergoing tracheotomy].

OBJECTIVE: To observe the impact of "Tongyuan" (regulating the Governor Vessel to tranquilize mental activities, conducting qi back to its origin) acupuncture treatment on cough reflex, pulmonary infection and swallowing function in stroke patients undergoing tracheotomy. METHODS: Seventy-four cerebral stroke patients with tracheo-tomy were randomly allocated to scalp acupuncture and "Tongyuan" acupuncture groups (n=37 in each group). All the patients of the two groups received basic treatment, including treatment of primary diseases, routine nursing, respiratory muscle training, physical therapy, acupuncture of Chize (LU5), Quchi (LI11), Hegu (LI4), Weizhong (BL40), Zusanli (ST36). In addition, for patients of the scalp acupuncture group, the middle 2/5 of Dingnieqianxiexian (MS6), the middle 2/5 of Dingniehouxiexian (MS7) and Dingpangerxian (MS9) on the contralateral side of lesions were punctured with filiform needles. For patients of the "Tongyuan" acupuncture group, Baihui (GV20), Zhongwan (GV12), Guanyuan (CV4), Qihai (CV6), Tianshu (ST25), Feishu (BL13), Pishu (BL20) were needled. The treatment in both groups lasted 30 minutes each time, once daily, 6 times a week for 4 weeks. The cough reflex grading score (CRGS, assessed according to cough, independent expectoration, sputum suction), clinical pulmonary infection score (CPIS, assessed according to the body temperature, white blood cell count, airway secretion in 24 h, PaO2/FiO2, infiltration status, cultured pathogenic bacteria), and swallowing function were evaluated by a researcher who was blinded to the grouping and treatment procedures. The success rate of extubation was calculated in a week at the end of treatments. RESULTS: After the treatment, the CRGS and CPIS of both groups were apparently decreased in comparison with their own pre-treatment (P<0.05), suggesting an improvement of the cough reflex and pulmonary infection. Regarding the swallowing function, of the two 37 cases in the scalp acupuncture and "Tongyuan" acupuncture groups, 9(24.3%) and 19(51.4%) experienced marked improvement, 12(32.5%)and 14(37.8%) were effective, and 16(43.2%) and 4(10.8%)failed in the treatment, with the effective rate being 56.8% and 89.2%, respectively. In regard to the successful extubation, of the two 37 cases in the scalp acupuncture and "Tongyuan" acupuncture groups, 5(13.5%) and 11(29.8%)had a marked improvement, 10(27.0%)and 18(48.6%)were effective, and 22(59.5%)and 8(21.6%)failed, with the effective rate being 40.5% and 78.4%, respectively. The therapeutic effect of "Tongyuan" acupuncture was significantly superior to that of scalp acupuncture in decreasing CRGS and CPIS, and in improving the swallowing function and raising the rate of successful extubation (P<0.05). CONCLUSION: "Tongyuan" acupuncture treatment can improve cough reflex to remove sputum, reduce pulmonary infection, enhance swallowing function, and raise the success rate of extubation in stroke patients, which is better than scalp acupuncture.