Prognostication of colorectal cancer liver metastasis by CE-based radiomics and machine learning.

The liver is the most common organ for the formation of colorectal cancer metastasis. Non-invasive prognostication of colorectal cancer liver metastasis (CRLM) may better inform clinicians for decision-making. Contrast-enhanced computed tomography images of 180 CRLM cases were included in the final analyses. Radiomics features, including shape, first-order, wavelet, and texture, were extracted with Pyradiomics, followed by feature engineering by penalized Cox regression. Radiomics signatures were constructed for disease-free survival (DFS) by both elastic net (EN) and random survival forest (RSF) algorithms. The prognostic potential of the radiomics signatures was demonstrated by Kaplan-Meier curves and multivariate Cox regression. 11 radiomics features were selected for prognostic modelling for the EN algorithm, with 835 features for the RSF algorithm. Survival heatmap indicates a negative correlation between EN or RSF risk scores and DFS. Radiomics signature by EN algorithm successfully separates DFS of high-risk and low-risk cases in the training dataset (log-rank test: p < 0.01, hazard ratio: 1.45 (1.07-1.96), p < 0.01) and test dataset (hazard ratio: 1.89 (1.17-3.04), p < 0.05). RSF algorithm shows a better prognostic implication potential for DFS in the training dataset (log-rank test: p < 0.001, hazard ratio: 2.54 (1.80-3.61), p < 0.0001) and test dataset (log-rank test: p < 0.05, hazard ratio: 1.84 (1.15-2.96), p < 0.05). Radiomics features have the potential for the prediction of DFS in CRLM cases.

Carbon-TiO2 Hybrid Quantum Dots for Photocatalytic Inactivation of Gram-Positive and Gram-Negative Bacteria.

Carbon-semiconductor hybrid quantum dots are classical carbon dots with core carbon nanoparticles doped with a selected nanoscale semiconductor. Specifically, on those with the nanoscale TiO2 doping, denoted as CTiO2-Dots, their synthesis and thorough characterization were reported previously. In this work, the CTiO2-Dots were evaluated for their visible light-activated antibacterial function, with the results showing the effective killing of not only Gram-positive but also the generally more resistant Gram-negative bacteria. The hybrid dots are clearly more potent antibacterial agents than their neat carbon dot counterparts. Mechanistically, the higher antibacterial performance of the CTiO2-Dots is attributed to their superior photoexcited state properties, which are reflected by the observed much brighter fluorescence emissions. Also considered and discussed is the possibility of additional contributions to the antibacterial activities due to the photosensitization of the nanoscale TiO2 by its doped core carbon nanoparticles.

Carbon Dots: Classically Defined versus Organic Hybrids on Shared Properties, Divergences, and Myths.

Carbon dots are defined as small carbon nanoparticles with effective surface passivation via organic functionalization. The definition is literally a description of what carbon dots are originally found for the functionalized carbon nanoparticles displaying bright and colorful fluorescence emissions, mirroring those from similarly functionalized defects in carbon nanotubes. In literature more popular than classical carbon dots are the diverse variety of dot samples from "one-pot" carbonization of organic precursors. On the two different kinds of samples from the different synthetic approaches, namely, the classical carbon dots versus those from the carbonization method, highlighted in this article are their shared properties and apparent divergences, including also explorations of the relevant sample structural and mechanistic origins for the shared properties and divergences. Echoing the growing evidence and concerns in the carbon dots research community on the major presence of organic molecular dyes/chromophores in carbonization produced dot samples, demonstrated and discussed in this article are some representative cases of dominating spectroscopic interferences due to the organic dye contamination that have led to unfound claims and erroneous conclusions. Mitigation strategies to address the contamination issues, including especially the use of more vigorous processing conditions in the carbonization synthesis, are proposed and justified.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

On the myth of "red/near-IR carbon quantum dots" from thermal processing of specific colorless organic precursors.

Carbon dots were originally found and reported as surface-passivated small carbon nanoparticles, where the effective surface passivation was the chemical functionalization of the carbon nanoparticles with organic molecules. Understandably, the very broad optical absorptions of carbon dots are largely the same as those intrinsic to the carbon nanoparticles, characterized by progressively decreasing absorptivities from shorter to longer wavelengths. Thus, carbon dots are generally weak absorbers in the red/near-IR and correspondingly weak emitters with low quantum yields. Much effort has been made on enhancing the optical performance of carbon dots in the red/near-IR, but without meaningful success due to the fact that optical absorptivities defined by Mother Nature are in general rather inert to any induced alterations. Nevertheless, there were shockingly casual claims in the literature on the major success in dramatically altering the optical absorption profiles of "carbon dots" by simply manipulating the dot synthesis to produce samples of some prominent optical absorption bands in the red/near-IR. Such claims have found warm receptions in the research field with a desperate need for carbon dots of the same optical performance in the red/near-IR as that in the green and blue. However, by looking closely at the initially reported synthesis and all its copies in subsequent investigations on the "red/near-IR carbon dots", one would find that the "success" of the synthesis by thermal or hydrothermal carbonization processing requires specific precursor mixtures of citric acid with formamide or urea. In the study reported here, the systematic investigation included precursor mixtures of citric acid with not only formamide or urea but also their partially methylated or permethylated derivatives for the carbonization processing under conditions similar to and beyond those commonly used and reported in the literature. Collectively all of the results are consistent only with the conclusion that the origins of the observed red/near-IR optical absorptions in samples from some of the precursor mixtures must be molecular chromophores from thermally induced chemical reactions, nothing to do with any nanoscale carbon entities produced by carbonization.

Standard Operating Procedures for Chinese Medicine Data Monitoring Committees of Clinical Studies.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Carbon Dots as Potent Antimicrobial Agents.

Carbon dots (CDots) have emerged to represent a highly promising new platform for visible/natural light-activated microbicidal agents. In this article, the syntheses, structures, and properties of CDots are highlighted, representative studies on their activities against bacteria, fungi, and viruses reviewed, and the related mechanistic insights discussed. Also highlighted and discussed are the excellent opportunities for potentially extremely broad applications of this new platform, including theranostics uses.

Carbon Dots: Zero-Dimensional Carbon Allotrope with Unique Photoinduced Redox Characteristics.

Carbon dots (CDots) exploit and enhance the intrinsic properties of small carbon nanoparticles. Their optical absorptions and photoinduced redox characteristics are competitive with those of conventional semiconductor quantum dots at one end and fullerenes and other carbon nanomaterials at the other. Highlighted in this mini review are the effective photon harvesting over a broad spectral range by CDots and their subsequent excited-state charge transfer processes and interactions, which have enabled their use as sensors, for photodynamic effects, and in various energy conversion technologies.

The add-on effect of dengzhan shengmai capsules on secondary prevention of ischemic stroke: A multicentre, randomised, placebo-controlled clinical trial.

OBJECTIVE: The Dengzhan Shengmai (DZSM) capsule is a commercially available type of Chinese herbal medicine frequently administered to improve neurological impairment after stroke. Its ability to prevent recurrent stroke, however, has not been determined. This study therefore evaluated the ability of DZSM as an add-on to conventional secondary preventive agents to prevent recurrent ischemic stroke. METHODS: In this randomised, double-blind, placebo-controlled trial, conducted at 83 hospitals in Mainland China, 3143 patients in 14-180 days after the initial onset of ischemic stroke, were randomly allocated to the DZSM (0.36 g, twice daily for 12 months) or the placebo group. All patients in both groups received standard secondary preventive medications. The primary outcome was the 1-year incidence of stroke. Between group differences were assessed using the Cox proportional hazards model. RESULTS: Intent-to-treat analysis showed that 58 (3.8%) participants in the DZSM group and 82 (5.4%) in the placebo group experienced new stroke events (hazard ratio = 0.70, 95% confidence interval = 0.50-0.98, P = 0.036). The type and incidence of adverse events were similar in the DZSM and placebo groups. CONCLUSIONS: The addition of DZSM capsules to standard secondary preventive agents provides additional benefits after the initial onset of ischemic stroke, reducing recurrent stroke without increasing severe adverse events. However, further study is needed to elucidate the role of DZSM on the updated practice of conventional secondary prevention for ischemic stroke.

Does Routine Anti-Osteoporosis Medication Lower the Risk of Fractures in Male Subjects? An Updated Systematic Review With Meta-Analysis of Clinical Trials.

Background: Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the specific efficacy of anti-osteoporosis medication for male subjects remains largely unexplored. Objective: The aim of this study was to evaluate the correlation between anti-osteoporosis medication and the risk of fracture in relation to low bone mass [including outcomes of osteoporosis, fracture, and bone mineral density (BMD) loss] in male subjects analyzed in studies within the updated literature. Methods: Randomized controlled trials (RCTs) that analyzed the effectiveness of a treating prescription for male subjects with osteoporosis (or low BMD) and that focused on the outcomes of fracture were included. Relevant studies from Embase, Web of Science, PubMed, and Chinese database of CNKI were retrieved from inception to January 30th, 2019. Two staff members carried out the eligibility assessment and data extraction. The discrepancies were settled by consultation with another researcher. We calculated the pooled relative risks (RRs) based on 95% confidence intervals (CIs). Results: Twenty-seven documents (28 studies) with 5,678 subjects were identified. For the category of bisphosphonates, significant results were observed in pooled analyses for decreased risk of the vertebral fracture domain (RR, 0.44 [95% CI, 0.31-0.62]), nonvertebral fracture domain (RR, 0.63 [95% CI, 0.46-0.87]), and clinical fracture domain (RR, 0.59 [95% CI, 0.48-0.72]) compared with those of controls. Participants with bisphosphonates had a 56% (95% CI = 38-69%) lower risk of vertebral fractures, 37% (95% CI = 13-54%) lower risk of nonvertebral fractures, and 41% (95% CI = 28-52%) lower risk of clinical fractures. Furthermore, meta-analyses also demonstrated a decreased risk of the vertebral fracture domain via treatment with risedronate (RR, 0.45 [95% CI, 0.28-0.72]) and alendronate (RR, 0.41 [95% CI, 0.23-0.74]), but not with calcitriol, calcitonin, denosumab, ibandronate, monofluorophosphate, strontium ranelate, teriparatide, or zoledronic acid, compared with that of controls. Conclusions: This systematic review confirms that bisphosphonates were connected with a decreased risk of vertebral fractures, nonvertebral fractures, and clinical fractures for male subjects with osteoporosis. Future research is needed to further elucidate the role of nonbisphosphonates in treating fractures of osteoporosis subjects.

Effects of carbon dots surface functionalities on cellular behaviors - Mechanistic exploration for opportunities in manipulating uptake and translocation.

Carbon dots (CDots) for their excellent optical and other properties have been widely pursued for potential biomedical applications, in which a more comprehensive understanding on the cellular behaviors and mechanisms of CDots is required. For such a purpose, two kinds of CDots with surface passivation by 3-ethoxypropylamine (EPA-CDots) and oligomeric polyethylenimine (PEI-CDots) were selected for evaluations on their uptakes by human cervical carcinoma HeLa cells at three cell cycle phases (G0/G1, S and G2/M), and on their different internalization pathways and translocations in cells. The results show that HeLa cells could internalize both CDots by different pathways, with an overall slightly higher internalization efficiency for PEI-CDots. The presence of serum in culture media could have major effects, significantly enhancing the cellular uptake of EPA-CDots, yet markedly inhibiting that of PEI-CDots. The HeLa cells at different cell cycle phases have different behaviors in taking up the CDots, which are also affected by the different dot surface moieties and serum in culture media. Mechanistic implications of the results and the opportunities associated with an improved understanding on the cellular behaviors of CDots for potentially the manipulation and control of their cellular uptakes and translocations are discussed.

Kai Xin San ameliorates scopolamine-induced cognitive dysfunction.

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Can Dietary Intake of Vitamin C-Oriented Foods Reduce the Risk of Osteoporosis, Fracture, and BMD Loss? Systematic Review With Meta-Analyses of Recent Studies.

Background: Several epidemiological studies have been performed to evaluate the association of dietary intake of vitamin C-oriented foods (DIVCF) with risk of fracture and bone mineral density (BMD) loss, but the results remain controversial. Therefore, we conducted a systematic meta-analysis to assess this correlation. Methods: We searched EmBase, PubMed, Web of Science, and the Chinese database CNKI for relevant articles published up to August 2019. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Discrepancies were resolved by consultation with a third expert. Results: A total of 13 eligible articles (including 17 studies) with 19,484 subjects were identified for the present meta-analysis. The pooled RR of hip fracture for the highest vs. lowest category was 0.66 (95% CI, 0.47-0.94) for DIVCF, i.e., people with a greater frequency of Vitamin C uptake had a 34% (95% CI, 6%-53%) lower prevalence of hip fracture. In subgroup analyses stratified by study design, gender, and age, the negative associations were statistically significant. Furthermore, the statistical analysis of the association between DIVCF and risk of osteoporosis (RR, 0.66; 95% CI, 0.48-0.92), BMD at the lumbar spine (pooled r, 0.15; 95% CI, 0.09-0.23), and BMD at the femoral neck (pooled r, 0.20; 95% CI, 0.11-0.34) showed beneficial effects of DIVCF. Conclusion: Our meta-analysis indicates that DIVCF is negatively associated with the risk of hip fracture, osteoporosis, and BMD loss, suggesting that DIVCF decreases the risk of hip fracture, osteoporosis, and BMD loss.

Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS: Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS: 32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION: The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.

An exploration of the role of a fish-oriented diet in cognitive decline: a systematic review of the literature.

Epidemiological studies have presented inconsistent evidence of the correlation between a fish-oriented dietary intake (FDI) and the risk of cognitive decline. To address these controversies, we performed this systematic review of prospective studies published in December 2016 and earlier using PubMed, Embase, and Web of Science. Two independent researchers conducted the eligibility assessment and data extraction; all discrepancies were solved by discussion with a third researcher. The pooled relative risks (RRs) focused on the incidence of events were estimated with 95% confidence intervals (CIs). Overall, nine studies containing 28,754 subjects were analyzed. When the highest and lowest categories of fish consumption were compared, the summary RR for dementia of Alzheimer type (DAT) was 0.80 (95%CI = 0.65-0.97); i.e., people with a higher intake of fish had a 20% (95%CI = 3-35%) decreased risk of DAT. Additionally, the dose-response synthesized data indicated that a 100-g/week increase in fish intake reduced the risk of DAT by an additional 12% (RR = 0.88, 95%CI = 0.79-0.99). Non-significant results were observed for the risk of dementia of all causes (DAC) and mild cognitive impairment (MCI). Limited evidence involving heterogeneity was found within subgroups or across studies. In conclusion, this review confirmed that a higher intake of fish could be correlated with a reduced risk of DAT. Further research, especially prospective studies that specifically quantify FDI, will help find a more accurate assessment of the different levels of dietary intake.

Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure.

Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal. Luxol-fast blue (LFB), immunohistochemical or immunofluorescence staining was used to detect morphological and biological changes in the brains. CPZ administration for 5 weeks resulted in completely demyelination and remyelination occurred when CPZ was withdrawn. ICA treatment during the recovery period for 1 week significantly improved myelin restoration, enhanced NF200-positive axons repair, increased the number of APC+/Olig2+ mature oligodendrocytes and prevented neuron-derived neurotrophic factor such as nerve growth factor (NGF) loss. Our results demonstrated that ICA treatment during the recovery period promotes remyelination and axon rewrapped, at least, in part, by promoting oligodendrogenesis and neurotrophic factor production.

Role of Medicinal Plants for Liver-Qi Regulation Adjuvant Therapy in Post-stroke Depression: A Systematic Review of Literature.

Current evidence demonstrated certain beneficial effects of medicinal herbs as an adjuvant therapy for post-stroke depression (PSD) in China; Chai-hu (Chinese Thorowax Root, Radix Bupleuri) is an example of a medicinal plant for Liver-Qi regulation (MPLR) in the treatment of PSD. Despite several narrative reports on the antidepressant properties of MPLR, it appears that there are no systematic reviews to summarize its outcome effects. Therefore, the aim of this review was to assess the effectiveness and safety of MPLR adjuvant therapy in patients with PSD. Seven databases were extensively searched from January 2000 until July 2016. Randomized control trials (RCTs) involving patients with PSD that compared treatment with and without MPLR were taken into account. The pooled effect estimates were calculated based on Cochrane Collaboration's software RevMan 5.3. Finally, 42 eligible studies with 3612 participants were included. Overall, MPLR adjuvant therapy showed a significantly higher effective rate (RR = 1.23; 95% CI = 1.19, 1.27; p < 0.00001) compared to those without. Moreover, the administration of MPLR was superior to abstainers regarding Hamilton Depression Scale (HAMD) score changes after 3 weeks (WMD = -4.83; 95% CI = -6.82, -2.83; p < 0.00001), 4 weeks (WMD = -3.25; 95% CI = -4.10, -2.40; p < 0.00001), 6 weeks (WMD = -4.04; 95% CI = -5.24, -2.84; p < 0.00001), 8 weeks (WMD = -4.72; 95% CI = -5.57, -3.87; p < 0.00001), and 12 weeks (WMD = -3.07; 95% CI = -4.05, -2.09; p < 0.00001). In addition, there were additive benefits in terms of response changes for the National Institutes of Health Stroke Scale (NIHSS) and other self-rating scores. No frequently occurring or serious adverse events were reported. We concluded that there is supporting evidence that adjuvant therapy with MPLR is effective in reducing the depressive symptoms and enhancing quality of life for patients with PSD. More well-designed RCTs are necessary to explore the role of MPLR in the treatment of PSD. Copyright © 2016 John Wiley & Sons, Ltd.

Is adjunctive treatment with medication of liver-soothing-oriented method beneficial for depression after cerebrovascular accident?: A PRISMA-compliant meta-analysis.

BACKGROUND: Adjunctive treatment with medication of liver-soothing-oriented method (MLSM) is one of the most commonly used approaches for subjects with depression after cerebrovascular accident (DCVA) in China. The purpose of this meta-analysis was to evaluate the outcome of MLSM treatment in subjects with DCVA using relevant published literature. METHODS: The PubMed, Cochrane Library, Embase, Chinese databases of China National Knowledge Infrastructure, WanFang, Sinomed, and VIP were used to collect all publications until March 2016. Randomized controlled trials comparing treatments with and without MLSM for subjects with DCVA were included. The quality of each publication was assessed based on the recent Handbook (5.1 version) for Cochrane Reviewers. Cochrane Collaboration's software RevMan 5.3 software was applied for data analysis. RESULTS: Thirty studies, including 2599 cases, were identified and collected. Adjunctive treatment with MLSM noticeably enhanced total effective rates (odds ratio 3.76; 95% confidence interval [CI] 2.92-4.85, I = 0%, P = 0.96) in comparison to non-MLSM conventional pharmacotherapy. Compared to non-MLSM treatment, the changes of Hamilton Depression Scale in adjunctive treatment with MLSM, respectively, decreased and showed beneficial effects after 3 weeks (weighted mean difference [WMD] -4.83; 95% CI -6.82 to -2.83; I = 86%, P < 0.001), 4 weeks (WMD -4.20; 95% CI -5.06 to -3.33; I = 78%, P < 0.001), 6 weeks (WMD -3.36; 95% CI -4.05 to -2.68; I = 54%, P = 0.02), 8 weeks (WMD -4.83; 95% CI -5.62 to -4.04; I = 73%, P < 0.001), and 12 weeks (WMD -2.88; 95% CI -4.09 to -1.67; I = 58%, P = 0.09). As for changes in inflammatory cytokine levels, adjunctive treatment with MLSM was associated with a significant decrease in tumor necrosis factor-α, IL-6, and interleukin-1ß levels in comparison to non-MLSM treatment. Moreover, there were positive effects on score changes for National Institute of Health Stroke Scale, activities of daily living, Hamilton Anxiety Scale, Modified Edinburgh Scandinavian Stroke Scale, and Self-Rating Anxiety Scale. No serious adverse events were reported. CONCLUSION: MLSM appears to improve symptoms of depressive disorders, enhance immediate responses, and the quality of life in subjects with DCVA. The positive action of MLSM might be potentially connected with its immunoregulating effects. More prospective trials with strict design and larger sample sizes are warranted to clarify its effectiveness and safety.

Do Chinese Researchers Conduct Ethical Research and Use Ethics Committee Review in Clinical Trials of Anti-Dementia Drugs? An Analysis of Biomedical Publications Originating from China.

BACKGROUND: Medical research using human participants must conform to the basic ethical principles found in the Declaration of Helsinki (DoH) of the World Medical Association. OBJECTIVE: The purpose of this review was to assess whether journals in China have improved in regard to the fulfillment of ethical disclosure procedures for clinical trials of anti-dementia drugs. METHODS: Four medical databases were searched for articles reporting clinical trials of oral anti-dementia drugs published in China in 2003, 2009, and 2014. The frequencies of reporting of informed consent from participants (ICP), approval of a regional ethical committee (REC), reference to DoH, and study registration were estimated respectively. Statistical analyses were conducted with SPSS v21 software. RESULTS: Among those randomized controlled trials published in 2003, 2009, and 2014, disclosure of REC approval was present for 2.67%, 1.15%, and 6.84%; statements of ICP were included in 9.33%, 7.76%, and 17.34%; reference to DoH was found for 4.00%, 1.44%, and 7.45%; and study registration reporting was included in 2.67%, 2.59%, and 9.28%, respectively. Improvements to reporting rates between 2009 and 2014 were seen, with more than twice as many trials reporting REC approval, ICP, reference to DoH, and study registration compared with 2009. CONCLUSION: Compared with 2003 and 2009, reporting rates for REC approval, ICP, reference to DoH, and study registration for clinical trials of anti-dementia drugs were enhanced in 2014 in the major medical journals of China. However, biomedical publications without definite statements of ethical considerations remain common, and this continues to be seen in Chinese journals. It is imperative that measures are taken to reinforce the ethical protection in clinical trials in China.