The impact of blinding on estimated treatment effects in randomized clinical trials on acupuncture: A meta-epidemiological study.

OBJECTIVE: To evaluate the sole impact of blinding patients and outcome assessors in acupuncture randomized controlled trials (RCTs) on treatment effects while considering the type of outcome measures. METHODS: We searched databases for the meta-analyses on acupuncture with both blinded and non-blinded RCTs. Mixed-effects meta-regression models estimated the average ratio of odds ratios (ROR) and differences in standardized mean differences (dSMD) for non-blinded RCTs versus blinded mixed-effects meta-regression model. RESULTS: The study included 96 meta-analyses (1012 trials). The average ROR for lack of patient blinding was 1.08 (95% confidence intervals 0.79-1.49) in 18 meta-analyses with binary patient-reported outcomes. The average ROR for lack of outcome assessor blinding was 0.98 (0.77-1.24) in 43 meta-analyses with binary subjective outcomes. The average dSMD was -0.38 (-0.96 to 0.20) in 10 meta-analyses with continuous patient-reported outcomes. The average dSMD was -0.13 (-0.45 to 0.18) in 25 meta-analyses with continuous subjective outcomes. The results of the subgroup analysis were consistent with the primary analysis findings. CONCLUSIONS: Blinding of participants and outcome assessors does not significantly influence acupuncture treatment efficacy. It underscores the practical difficulties of blinding in acupuncture RCTs and the necessity to distinguish between trials with and without successful blinding to understand treatment expectations' effects. Enhancing blinding procedures' quality and assessment in future research is crucial for improving RCTs' internal validity and reliability.

Simultaneous nitrogen and phosphorus removal through an integrated partial-denitrification/anammox process in a single UAFB system.

With the aim of obtaining enhanced nitrogen removal and phosphate recovery in mainstream sewage, we examined an integrated partial-denitrification/anaerobic ammonia oxidation (PD/A) process over a period of 189 days to accomplish this goal. An up-flow anaerobic fixed-bed reactor (UAFB) used in the integrated PD/A process was started up with anammox sludge inoculated and the influent composition controlled. Results showed that the system achieved a phosphorus removal efficiency of 82% when the influent concentration reached 12.0 mg/L. Batch tests demonstrated that stable and efficient removal of chemical oxygen demand (COD), nitrogen, and phosphorus was achieved at a COD/NO3--N ratio of 3.5. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analysis indicated that hydroxyapatite was the main crystal in the biofilm. Furthermore, substrate variation along the axial length of UAFB indicated that partial denitrification and anammox primarily took place near the reactor's bottom. According to a microbiological examination, 0.4% of the PD/A process's microorganisms were anaerobic ammonia oxidizing bacteria (AnAOB). Ca. Brocadia, Ca. Kuenenia, and Ca. Jettenia served as the principal AnAOB generals in the system. Thauera, Candidatus Accumulibacter, Pseudomonas, and Acinetobacter, which together accounted for 27% of the denitrifying and phosphorus-accumulating bacteria, were helpful in advanced nutrient removal. Therefore, the combined PD/A process can be a different option in the future for sewage treatment to achieve contemporaneous nutrient removal.

A search of only four key databases would identify most randomized controlled trials of acupuncture: A meta-epidemiological study.

Little research has been conducted to assess which specific databases should be searched when performing a systematic review (SR) on acupuncture. The current study aimed to identify key databases and the optimal database combination to retrieve randomized controlled trials (RCTs) on acupuncture for inclusion in SRs. A systematic search for SRs in the field of acupuncture was conducted in order to identify target databases and RCTs were extracted from the SRs that had searched all target databases. The proportions of SRs that had achieved 100%, 95%, or 90% recall of RCTs and the total recall of RCTs in various combinations of target databases were calculated. Sensitivity analysis was performed on those SRs that included 10 or more RCTs. CNKI, WanFang, VIP, PubMed, CENTRAL and Embase were regarded as target databases. A total of 4349 acupuncture RCTs were extracted from 286 SRs. Searching all six target databases retrieved 99.3% of all RCTs while 99.1% were recalled by searching the combination of CNKI, WanFang, PubMed and CENTRAL. There were no significant differences on total recall of RCTs (p = 0.549) or in the proportion of SRs with 90% recall of RCTs (97.2% vs. 97.6%; p = 0.794) between searching the above four and the full six target databases. Most results were similar in the sensitivity analysis. The combined retrieval power of CNKI, WanFang, PubMed and CENTRAL was considered an efficient choice to retrieve acupuncture RCTs included in SRs.

Spiky titanium dioxide nanoparticles-loaded Plantaginis Semen polysaccharide as an adjuvant to enhance immune responses.

The purpose of this study was to prepare spiky titanium dioxide nanoparticles-loaded Plantaginis Semen polysaccharide (SN-TiO2-PSP), and the structural characterization and immune response of infectious laryngotracheitis (ILT) vaccine in Hetian chickens were investigated. The structural characterization of SN-TiO2-PSP was analyzed by FT-IR, TEM, and TGA analysis. And the immune organs indexes, lymphocytes proliferation, specific antibody levels, and ratios of CD4+ and CD8+ T lymphocytes were studied. Structural characterization results showed that SN-TiO2-PSP has a typical polysaccharide absorption peak and good stability. The SN-TiO2-PSP's shape was similar to sea urchin, and its zeta potential and particle size were 27.56 mV and 976.11 nm, respectively. In vivo results showed that SN-TiO2-PSP could enhance the proliferation of peripheral lymphocytes, specific antibody levels, CD4+ and CD8+ T lymphocytes ratios, IL-4 and INF-γ levels in Hetian chickens vaccinated with ILT vaccine on D7, D14, D21, and D28. In addition, SN-TiO2-PSP not only enhanced the indexes of immune organs but also promoted the development of immune organs. Therefore, SN-TiO2-PSP has immune adjuvant activity and may become a new potential immune adjuvant.

Erzhi Tiangui Granules Improve In Vitro Fertilization Outcomes in Infertile Women with Advanced Age.

BACKGROUND: The fertility of females with advanced age declines with aging. Therefore, for medical and social reasons, it is important to establish mechanisms to protect and improve the fertility of such populations. With widespread use of traditional Chinese medicine (TCM) in in vitro fertilization (IVF), studies have evaluated their impact on improving the fertility of females with advanced age. In this study, we performed proteomic analysis of follicular fluid to reveal mechanisms of the Erzhi Tiangui (EZTG) granule (Chinese herbs for replenishing vital essence to tonify the kidney) in improving the outcomes of IVF in infertile women with advanced age. METHODS: This was a randomized, double-blind, and placebo-controlled trial in which 100 patients with advanced age were divided into the EZTG group and the placebo group by the random number table plus envelope method. Both groups were subjected to controlled ovarian stimulation with a GnRH antagonist regimen. Differences between the two groups were evaluated, including the TCM syndrome score after treatment, gonadotrophin (Gn) days and Gn doses, the number of retrieved oocytes, 2 pronucleus (PN) fertilization, 2PN cleavage, and high-quality embryos. Differentially expressed proteins were identified using the LC-MS/MS method, and their functions were determined through bioinformatics analyses. RESULTS: The number of high-quality embryos in the placebo group was significantly lower than that in the EZTG group (2.88 ± 1.85 vs. 4.13 ± 2.83, p=0.011). Eleven differentially expressed proteins were identified between the two groups. Four proteins were highly expressed, whereas seven were suppressed in the control group, compared to the EZTG group. The overall trend suggested that the apoptotic effect in the follicular fluid of the EZTG group was downregulated. CONCLUSION: Treatment with the EZTG granule can improve embryo quality in IVF of advanced age females with both kidney Qi and Yin deficiency syndromes. The mechanism is attributed to downregulation of apoptotic-effector protein expressions in the follicular fluid. This trial is registered with ChiCTR1900025139.

Agreement of Risk-of -Bias varied in systematic reviews on acupuncture and was associated with methodological quality.

OBJECTIVES: The objective of the study was to evaluate the consistency of risk of bias assessments for overlapping randomized controlled trials (RCTs) included in systematic reviews (SRs) on acupuncture. STUDY DESIGN AND SETTING: Databases were searched for acupuncture SRs. A weighted kappa (κ) statistic was calculated, and logistic regression was used to explore the factors of disagreements. RESULTS: We included 241 RCTs from 109 SRs on acupuncture. The percentage disagreements ranged from 25% to 44%, with moderate agreement for random sequence generation (κ = 0.57), allocation concealment (κ = 0.50), and incomplete outcome data (κ = 0.50), besides fair agreement for blinding of participants and personnel (κ = 0.44), blinding of outcome assessment (κ = 0.31), and selective reporting (κ = 0.39). Only 19% RCTs were evaluated completely consistent. Methodological quality (random sequence generation, odds ratio (OR) = 3.46), international cooperation (allocation concealment, OR = 0.14; incomplete outcome data, OR = 0.14; selective reporting, OR = 0.05), and risk of bias reporting completeness score (selective reporting, OR = 0.53) significantly affected the relative odds of disagreements. CONCLUSION: The level of agreement varied from fair to moderate agreement depending on the risk of bias domain. Methodological quality appears to be an overarching factor to account for disagreements.

Use and reporting of risk of bias tools in 825 systematic reviews of acupuncture: a cross-sectional study.

OBJECTIVE: To assess the use and reporting of risk of bias (RoB) tools in systematic reviews (SRs) of acupuncture. STUDY DESIGN AND SETTING: We extracted and analyzed information relating to RoB in acupuncture SRs via Medline, Embase and the Chinese CNKI (Chinese National Knowledge Infrastructure), WanFang and VIP databases from their inception to 24 November 2017. Three subgroup analyses were used to check the influence of language, journal type and impact factor, following which we used descriptive analysis. RESULTS: We included 825 acupuncture SRs, of which 48% used the Cochrane RoB tool. Only 36% used the latest version of the Cochrane Handbook (version 5.1.0 at time of writing) with higher proportions among Cochrane SRs (65%) versus non-Cochrane SRs (34%), and high impact factor journals (58%) versus low or no impact factor journals (28% and 38%, respectively). In the last decade, there were notable increases in the use of the Cochrane RoB tool and Cochrane Handbook version 5.1.0, of 43% and 19%, respectively. Chinese-language SRs demonstrated proportionally higher tendencies to report an incorrect Cochrane Handbook version, increasing by 14% in the last 5 years. Additionally, 7% SRs did not report any results, and only 10% reported relatively complete and adequate RoB assessment. Cochrane SRs reported more complete assessments than Chinese-language or non-Cochrane English-language SRs. CONCLUSION: Use and reporting of RoB tools were suboptimal. Proportionally, use of the Cochrane RoB tool and Cochrane Handbook version 5.1.0 was low but rising. Our results highlight the prevalence and concerns of using unsuitable tools and the issue of incomplete RoB reporting. RoB tool application requires further improvement.

Do acupuncture trials have lower risk of bias over the last five decades? A methodological study of 4 715 randomized controlled trials.

OBJECTIVE: To evaluate the change of the risk of bias (RoB) of acupuncture randomized controlled trials (RCTs) in the past five decades. METHODS: Multiple databases were searched. We included RCTs identified from systematic reviews (SRs) on acupuncture. General characteristics and RoB judgment for each domain were extracted. The proportions of RCTs at high and unclear RoB were calculated and the changes were examined by the Mann-Kendall test. RESULTS: We included 368 SRs including 4 715 RCTs. The rates of RCTs at unclear RoB were the highest in allocation concealment (63%), and at the lowest in incomplete outcome data (35%); in the last five decades, statistically significant reductions were found for random sequence generation (P < 0.001) and selective reporting (P = 0.01), and increases for blinding of participants and personnel (P < 0.001), blinding of outcome assessment (P < 0.001) and incomplete outcome data (P = 0.04). For the proportions of RCTs at high RoB, blinding of participants and personnel (47%) and blinding of outcome assessment (35%) were the poorest domains; there were no significant differences in changes for all domains. CONCLUSIONS: Although improvements concerning unclear risk were observed for random sequence generation and selective reporting, major issues remain for allocation concealment and blinding. It is imperative to use valid randomization, specify how it is conducted, and try to test for selection bias and the success of masking by using the Berger Exner test.

Risk of bias assessments and reporting quality of systematic reviews and randomized controlled trials examining acupuncture for depression: An overview and meta-epidemiology study.

OBJECTIVES: To assess the use of risk of bias (ROB) assessment tools and the reporting quality of ROB assessment results in systematic reviews (SRs) of acupuncture for depression, as well as to evaluate the ROB of depression-related randomized controlled trials (RCT). METHODS: Embase, Medline, Chinese Journal Full-Text Database (CJFD), VIP Chinese Technology Periodical Database, and WanFang Data Resource System of Digital Periodicals were searched from their inception to 24 November 2017. SRs of RCTs concerning acupuncture on depression were included. General characteristics and the information related to risk of bias in SRs were extracted. A descriptive analysis was used. RESULTS: Thirty-nine SRs were included. Of these, two (5%) did not perform a ROB assessment, 18.9% did not report the ROB assessment results, and 62.2% did not report the assessment results of each ROB item. Text descriptions and tables were commonly used in reporting forms. Only 32.4% of SRs reported support for judgment. The reporting rate of ROB assessment results was low in all items (13.5%-35.1%). Regarding RCTs, 59.7% used adequate randomization methods, 13.1% performed adequate allocation concealment, 12.5% performed adequate blinding of participants and personnel, 27.3% performed adequate blinding of the assessment outcomes, and 41.5% and 49.3% had a low ROB in terms of incomplete outcome data and selective outcome reporting, respectively. CONCLUSION: For the SRs of acupuncture for depression, the selection of ROB assessment tools needs to be optimized. The reporting quality is poor, and the overall ROB of RCTs is high. Therefore, the results may not be reliable.

Intracellular pH-propelled assembly of smart carbon nanodots and selective photothermal therapy for cancer cells.

A kind of smart carbon nanodots (CNDs) with the pH response feature was prepared by the one-pot hydrothermal treatment of citric acid and dicyandiamide, which was used for the differentiation of cancer/normal cells and the selective photothermal therapy (PTT) of cancer cells. When the smart CNDs were cultured with cells, they were highly internalized in the lysosomes of cells. Since the small-sized CNDs (about 5 nm) tends to form aggregation (as large as about 20 nm or even larger) under an acid condition (pH = 4.7) due to the electrostatic attraction produced by the surface protonation, relatively severer aggregation of the CNDs were observed in liver cancer cells (HepG2 cells) relative to normal ones (LO2 cells) due to a relative lower pH in the lysosomes of HepG2 cells, which endows them a new strong absorption band at longer wavelengths (450-900 nm) and a higher photothermal conversion efficiency (42.13 %), benefiting to differentiated PTT. The flow cytometric data indicates strong photothermal ablation (8 min, 509.6 mW/cm2) for cancer cells with the assistance of these smart CNDs achieves 82 % death rate of cancer cells, while much less damage is observed on the normal cells (6.35 %). To the best of our knowledge, this is the first report about CNDs for selective PTT owing to their intrinsic property without the aid of any other targeting ligands. These smart CNDs are also available for other acid-responsive sensing systems, and this study inspires us in the synthesis of near-infrared featured carbon materials.

Zymolytic Grain Extract (ZGE) Significantly Extends the Lifespan and Enhances the Environmental Stress Resistance of Caenorhabditis elegans.

Many reports have shown that grains play an important role in our daily lives and can provide energy and nutrients to protect us from various diseases, and they are considered to be indispensable parts of our lives. It has been reported that some constituents in grains could exert functional effects against HIV infections and multiple cancers. Zymolytic grain can produce some new useful molecules and thus support the cell nutrients in the human body. In this study, the effects of zymolytic grain extract (ZGE) supernatants on the changes of nematode indicators were investigated, including lifespan, self-brood size, and body length in environmental conditions (temperature, ultraviolet radiation or 5-fluoro-2'-deoxyuridine (FUDR) stimuli). We found that, compared to the control group, the ZGE supernatant-feeding group could prolong the lifespan of nematodes under normal conditions. More importantly, ZGE supernatants could improve the ability of nematodes to resist stress. When the concentration of FUDR was 400 or 50 µM, the ZGE supernatant-feeding group could prolong lifespan by an average of 38.4% compared to the control group, and the eggs of the ZGE supernatant-feeding group could hatch and develop into adults. These results indicated that ZGE could protect C. elegans from external stress and thus prolong their lifespan and improve the physiological state of nematodes. Therefore, ZGE supernatant has potential to be used as a nutritional product in antioxidant and anti-aging research.

Antimicrobial activity of saponins produced by two novel endophytic fungi from Panax notoginseng.

Endophytes in plants may be co-producer of the bioactive compounds of their hosts. We conducted a study to bioprospect for saponin-producing endophytic fungi from Panax notoginseng and evaluate the antimicrobial activity of saponins. Two novel fungal endophytes, Fusarium sp. PN8 and Aspergillus sp. PN17, were isolated from traditional Chinese medicinal herb P. notoginseng. After eight days of fermentation, the total saponins produced in the culture broth of PN8 and PN17 were 1.061 and 0.583 mg mL-1, respectively. The saponin extracts exhibited moderate to high (inhibition zone diameter 15.7-28.4 mm, MIC 1.6-12.5 mg mL-1) antimicrobial activity against pathogens tested. Further analysis showed that triterpenoid saponins produced by Fusarium PN8 were Rb1, Rd and 20(S)-Rg3, while Aspergillus PN17 had the ability to synthesise ginsenoside Re, Rd and 20(S)-Rg3. The isolated endophytes may be used as potential sources for microbial production of plant secondary metabolites and for antimicrobial agents.

Start-up of granule-based denitrifying reactors with multiple magnesium supplementation strategies.

In the present work, the effect of Mg(2+) supplementation on the start-up of a denitrification process and the granulation of denitrifying sludge was investigated in three upflow anaerobic sludge blanket (UASB) reactors. The reactors R1 and R2 were continuously and intermittently, respectively, supplied with 50 mg L(-1) Mg(2+), whereas R0 was used as the control. The nitrogen loading rate (NLR) and organic loading rate (OLR) gradually increased, and extremely high values were obtained (36.0 kgN m(-3) d(-1) and 216.0 kgCOD m(-3) d(-1), respectively). Granulation occurred in R1 first, but the reactor capacities were comparable. Suffering from starvation, the R0-R2 performances were comparable. At the end of the experiment, the average diameter of the granules in R0, R1, and R2 were 1.67, 1.72 and 1.68 mm, respectively, and the settling velocities of the granules in R1 and R2 were 1.14-fold the speed of R0. The specific denitrifying activity (SDA) of the sludge from the reactors supplied with Mg(2+) was greater than the reactor without Mg(2+). Intermittent Mg(2+) supplementation was identified as the best choice to be utilized to cultivate denitrifying granules, which was consistent with kinetic analysis.

Free radical scavenging activity of red ginseng aqueous extracts.

This study was performed to investigate the free radical scavenging activity of Panax red ginseng C.A. Meyer aqueous extract on 1,1-dipheny-2-picrylhydrazyl (DPPH), carbon-centered radical, hydroxyl and superoxide radicals using Electron Spin Resonance (ESR) spectrometer and spin-trapping techniques. Two different Red ginseng aqueous extracts prepared by boiling water or room temperature extraction exhibited no significant difference in free radical scavenging activity. Ginseng extracts completely eliminated DPPH radical at 2 mg/ml. About 0.5 mg/ml ginseng extracts quenched 80% carbon-centered free radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Hydroxyl radical and superoxide radical were generated by UV irradiation and trapped by 5,5-dimethyl-l-pyrroline-N oxide (DMPO). Ginseng extracts scavenged 40% of hydroxyl radical at 0.1 mg/ml. Two mg/ml ginseng extracts completely scavenged superoxide radical. Ginseng extracts did not scavenge nitric oxide. The ESR data demonstrate that red ginseng aqueous extract is not a strong free radical scavenger.