Study on the Application of Doxorubicin-Loaded Magnetic Nanodrugs in Targeted Therapy of Liver Cancer.

Doxorubicin (DOX) has been widely recognized as effective in anticancer therapy; however, the additional organ toxicity and low targeting of DOX in antitumor activity remains unaddressed. The aim of this study was to use the drug carrier dextran/polylactic acid (DEX/PLA) and paramagnetic Fe3O4 to improve the targeting of DOX in liver cancer treatment while reducing its potential organ toxicity. Our experimental results show that the combination drug (Fe3O4@DEX/PLA-DOX) exhibits strong hepatocarcinogenic inhibition and low cytotoxicity and that this modified drug provides a better option for clinical liver cancer treatment.

Using Mendelian randomization as the cornerstone for causal inference in epidemiology.

Mendelian randomization (MR) is attracting considerable critical attention. This paper aimed to explore the characteristics of the publications of MR, to reach an insight in this field and prospect the future trend. A bibliometric analysis was performed to identify published MR-related research. The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.9, and CiteSpace 5.7.R3 were used to analyze the information. A total of 1783 papers of MR were identified, and the first included literature appeared in 2003. A total of 2829 institutions from 72 countries participated in the relevant research, while the UK contributed to 852 articles and were in a leading position. The most productive institution was the University of Bristol, and Smith GD who has posted the most articles (n=202) was also from there. The Int J Epidemiol (100 publications, 6861 citations) was the most prolific and high citation journal. Related topics of frontiers will still focus on coronary heart disease, diabetes, cancer, psychiatric disorder, body mass index, and lifestyle factors. We summarized the publication information of MR-related literature from 2003 to 2020, including country and institution of origin, authors, and publication journal. We analyzed former research hotspots in the field of MR and predicted future areas of interest. Exposures and outcomes detected in this paper will be the hotspots and frontiers of research in the next few years.

An evidence mapping and scientometric analysis of the top-100 most cited clinical trials of anti-PD-1/PD-L1 drugs to treat cancers.

OBJECTIVE: To gain a deeper understanding of the hot topics and future prospects of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors treatment of cancer through scientometric analysis of the top-100 most cited clinical trials. MATERIALS AND METHODS: We searched the Web of Science Core Collection database from 1980 to June 2019. Two reviewers independently screened the top-100 most cited clinical trials that defined by the National Institutes of Health starting from the most cited article. Title, year of publication, citations, type of cancer, and focused aspects of outcomes were extracted from included clinical trials. VOSviewer software (version 1.6.9) and Excel 2016 were used to do statistical analysis. The evidence mapping was used to present the relationship between cancers, drugs, citations, and outcomes, etc. RESULTS: The top-100 most cited clinical trials published from 2010 to 2018 in nine journals with high impact factor (IF) (IF2018:6.68-70.67), and Lancet Oncology (USA) published the most clinical trials (n = 29, IF2018 = 35.3856). The total number of citations of the top-100 most cited clinical trials was from 59 to 5606. 920 authors from 34 countries and 458 organizations participated in publishing the top-100 most cited clinical trials. The USA (n = 95) and Memorial Sloan-Kettering Cancer Center (n = 31) contributed the most publications. Based on the evidence mapping, there are 25 different types of cancers (e.g. lung cancer, melanoma, and renal cell cancer) and five focused aspects of outcomes (e.g. safety and efficacy). CONCLUSION: The USA was the dominant country. Anti-PD-1/PD-L1 drugs were widely used to treat lung cancer, melanoma, renal cell cancer, and Hodgkin lymphoma. More exploration should be done to explore the use of anti-PD-1/PD-L1 drugs to treat more type of cancers in future research.

[Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases].

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

[Overview of systematic reviews on Shuxuening Injection].

This study aimed to analyze the methodological quality of systematic reviews of Shuxuening Injection and evaluate the efficacy and adverse reactions of Shuxuening Injection in the treatment of different diseases,in order to provide supportive evidence for clinical practice. Three Chinese databases and three English databases were retrieved to identify systematic reviews and Meta-analysis on the efficacy and safety of Shuxuening Injection in the treatment of diseases. The AMSTAR 2( a measurement tool to assess systematic reviews 2) tool was used to evaluate the methodological quality of the included systematic reviews,and tables were created to present the results of Meta-analyses. Twenty-four systematic reviews were included,all with very low methodological quality. Among the 16 AMSTAR-2 items,only 5 items had a compliance rate greater than 60. 0%,and 8 items had a compliance rate less than 50. 0%. For patients with cerebral infarction,Shuxuening Injection combined with conventional treatment was more effective than conventional treatment alone in terms of clinical efficiency and neurological deficit improvement. For patients with angina pectoris,Shuxuening Injection was superior to Danshen/Compound Danshen Injection in terms of the total effective rate of angina pectoris and total effective rate of ECG. The efficacy of Shuxuening Injection combined with conventional treatment is significantly better than conventional treatment.Shuxuening Injection( alone or combined with conventional treatments) was better than conventional treatments for cerebral hemorrhage,ischemic cerebrovascular disease,chronic pulmonary heart disease,vertigo and sudden deafness. Shuxuening Injection had better efficacy and lower incidence of adverse reactions,but the methodological quality of included systematic reviews was low. The results of this study still need to be verified by high-quality systematic reviews.

Prespecification of subgroup analyses and examination of treatment-subgroup interactions in cancer individual participant data meta-analyses are suboptimal.

OBJECTIVES: This study aimed to explore the prespecification and conduct of subgroup analyses in cancer individual participant data meta-analyses (IPDMAs). STUDY DESIGN AND SETTING: We searched PubMed, Embase.com, Cochrane Library, and Web of Science to identify IPDMAs of randomized controlled trials evaluating intervention effects for cancer. We evaluated how often cancer IPDMAs prespecify subgroup analyses and statistical approaches for examining treatment-subgroup interactions and handling continuous subgroup variables. RESULTS: We included 89 IPDMAs, of which 41 (46.1%) reported a statistically significant treatment-subgroup interaction (P < 0.05) in at least one subgroup analysis. 47 (52.8%) IPDMAs prespecified methods for conducting subgroup analyses and the remaining 42 (47.2%) did not prespecify subgroup analyses. Of the 47 IPDMAs prespecified subgroup analyses, 19 performed the planned subgroup analyses, 21 added subgroup analyses, 7 reduced subgroup analyses. Eighty IPDMAs examined treatment-subgroup interactions, but 72 IPDMAs did not provide enough information to determine whether an appropriate approach that avoided aggregation bias was used. 85 IPDMAs that used continuous variables in subgroup analyses categorized continuous variables and only 1 IPDMA examined non-linear relationships. CONCLUSION: Many cancer IPDMAs did not prespecify subgroup analyses, nor did they fully perform planned subgroup analyses. Lack of details for the test of treatment-subgroup interactions and examination of non-linear interactions was suboptimal.

A bibliometric analysis of global research output on network meta-analysis.

BACKGROUND: Network meta-analysis (NMA) has been widely used in the field of medicine and health, but the research topics and development trends are still unclear. This study aimed to identify the cooperation of countries and institutes and explore the hot topics and future prospects in the field of NMA. METHODS: Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace V, HistCite 2.1, and Excel 2016 to analyze literature information, including years, journals, countries, institutes, authors, keywords, and co-cited references. RESULTS: NMA research developed gradually before 2010 and rapidly in the following years. 2846 NMA studies were published in 771 journals in six languages. The PLoS One (110, 3.9%) was the most productive journal, and N Engl J Med (5904 co-citations) was the most co-cited journal. The most productive country was the United States (889, 31%) and the most productive institute was the University of Bristol (113, 4.0%). The active collaborations were observed between developed countries and between productive institutes. Of the top 10 authors, four were from the UK, and among the top 10 co-cited authors, six were from the UK. Randomized evidence, oral anti-diabetic drugs, coronary artery bypass, certolizumab pegol, non-valvular atrial fibrillation, and second-line antihyperglycemic therapy were the hot topics in this field. CONCLUSIONS: NMA studies have significantly increased over the past decade, especially from 2015 to 2017. Compared with developing countries, developed countries have contributed more to these publications and have closer cooperation, indicating that cooperation between developed and developing countries should be further strengthened. The treatment of diabetes, cardiovascular diseases, and immune rheumatism are the main hot topics.

Sjogren's syndrome in clinical trials of traditional Chinese medicine: protocol for the development of a core outcome set.

BACKGROUND: Sjogren's syndrome (SS) is a chronic autoimmune rheumatic disease with an incidence of 0.03 to 0.3%. In recent years, there are an increasing number of randomized controlled trials of traditional Chinese medicine (TCM) for SS. However, there are generally some problems in these published clinical trials: lack of reporting primary or long-term outcomes and the heterogeneous in different clinical trials' outcome. Our study aims to determine the priority outcomes and standard TCM syndromes for all stakeholders and reach agreement on the COS and syndromes to be measured and reported in all future TCM trials in patients with SS. METHODS AND ANALYSIS: A phase-wise refinement approach will be used, consisting of three phases, yet complementary, sub-work phases, whereby each phase will inform the next coming phases. The following are the three phases: (I-a) identifying of a long initial list of outcomes through systematic literature review and semi-structured qualitative interviews and (I-b) identifying an initial list of TCM syndromes through (1) systematic literature review, (2) referencing ancient Chinese medical books, and (3) retrospective studies of medical records; (II) prioritization of outcomes using Delphi survey with different stakeholders, such as health professionals and patients; and (III) through consensus meetings with patients and professionals to agree on the final COS and TCM syndromes. DISCUSSION: We summarized the actions of COS into three points: direct action, indirect action, and final action. After the final COSs is completed, we will publish this research in a journal to promote communication. TRIAL REGISTRATION: Core Outcome Measures in Effectiveness Trials Initiative (COMET) number 1429 . Registered on 01 December 2019.

The top-100 cited articles on biomarkers in the depression field: a bibliometric analysis.

This paper aimed to explore the characteristics of the top-100 cited articles on the biomarkers in the depression field and strive to find the future trend. The top-100 cited articles were selected from the Web of Science Core Collection database. Excel 2016 and VOSviewer 1.6.9 were used to analyze the information. Forty-six journals contributed to these 100 articles, and Biological Psychiatry published the largest number of articles (n = 18). Holsboer F (n = 4) contributed the most, and Maes M (n = 118) was the most co-cited author. Twenty-six countries and 220 organizations contributed to the top-100 articles, respectively. The USA (n = 48) was the main contributor. NIMH and Kings Coll London both participated in seven articles. Major depression (n = 62), depression (n = 38) and biomarker (n = 31) were the top three keywords. These results indicated that articles published in journals with higher impact factors are more likely to spread. Compared with developing countries, developed countries have contributed more to these articles. It is suggested that cooperation should be strengthened between developed countries and developing counties in the future. More research on biomarkers in the depression field may still mainly focus on major depression.Abbreviation: WoS = Web of Science; JCR = Journal Citation Reports; UK = United Kingdom; NIMH = The National Institute of Mental Health; UCL = University College London; IF = Impact factor; BDNF = brain-derived neurotrophic factor; USA = United States.

Top 100 most-cited articles on exosomes in the field of cancer: a bibliometric analysis and evidence mapping.

Several studies have demonstrated that exosomes have a very broad prospect in the field of cancer therapy. This study aims to identify the general characteristics, cooperation of authors, countries and explore the hot topics of the top 100 cited articles on tumor-related exosomes. We searched the Web of Science Core Collection on June 28, 2019, to collect related publications. Microsoft Excel 2016 and VOSviewer 1.6.9 were applied to analyze the publication year, citations, authors, countries, institutions, journals, and keywords. The top 100 articles were published between 1998 and 2017 with citations ranging from 181 to 2275. Cancer Research (n = 9) had the highest number of publications. Nature Cell Biology, Nature, and Nature Medicine are considered to be the core journals of tumor-related exosomes because they are among top 10 from different analytical perspectives. The USA (n = 49) and Harvard University (n = 9) were the most productive country and institution, respectively. There were active collaborations between countries. Kalluri R (n = 6) contributed the largest number of articles, and Taylor DD was the most co-cited author. Théry C and Al-Nedawi K are probably the two important experts as they are both the top 10 authors and top 10 co-cited authors. Three clusters were obtained after clustering analysis of the keywords. The main hot topics were the proteomic analysis and mechanism of vesicle activation and the role of exosomes in the diagnosis and progression of tumors. Further research should expand and develop new topics such as the role of exosomes in the treatment of cancers.

Efficacy and safety of herbal medicine (Lianhuaqingwen) for treating COVID-19: A systematic review and meta-analysis.

BACKGROUND: Lianhuaqingwen (LH) has been proven effective for influenza. However, the promotion of LH for the treatment of patients with COVID-19 remains controversial. Therefore, our study aimed to assess the efficacy and safety of Lianhuaqingwen (LH) in treating patients with COVID-19 by a systematic review and meta-analysis. METHODS: We conducted the literature search using six electronic databases from December 1, 2019, to June 2, 2020. Cochrane Risk of Bias tool was used to assess the quality of randomized controlled trials. Newcastle-Ottawa Scale was used to assess the quality of case control studies. Agency for Healthcare Research and Quality checklist was used to assess the quality of case series. All analyses were conducted by RevMan 5.3. For outcomes that could not be meta-analyzed were performed a descriptive analysis. RESULTS: Eight studies with 924 patients were included. Three studies were RCTs, three were case control studies, and two were case series. The quality of the included studies was poor. Compared with patients treated by conventional treatment, patients treated by LH combined with conventional treatment have a higher overall effective rate (RR = 1.16, 95%CIs: 1.04∼1.30, P = 0.01) and CT recovery rate (RR=1.21, 95%CIs: 1.02∼1.43, P = 0.03). Patients of LH groups have a lower incidence of diarrhea (5.6% vs.13.4%), and have statistically significant (P = 0.026). But the rate of abnormal liver function in the combined medication group is higher than that in the single LH group. CONCLUSION: LH combined with conventional treatment seems to be more effective for patients with mild or ordinary COVID-19.

Inconsistency and low transparency were found between core outcome set protocol and full text publication: a comparative study.

OBJECTIVES: The objective of the study was to assess inconsistencies between individual protocols and associated full-text publications in the development of core outcome sets (COSs). STUDY DESIGN AND SETTING: Protocols and subsequent full-text publications were retrieved by searching the following electronic databases: PubMed, Embase, Web of Science, and the Core Outcome Measures in Effectiveness Trials database from inception to October 1, 2019. We summarized changes in the general and methodological characteristics by comparing the protocols with the full-text publications and reported change as information frequency and proportion. RESULTS: A total of 24 protocols and 32 corresponding full-text publications that encompassed 14 study topics were identified from databases. In the identified initial list of outcomes, five COSs (20.8%) changed the included study type, none of which explained the reasons for these changes. In addition, eight COSs showed inconsistencies between the protocols and full-text publications in the searched databases, of which, only two studies explained the reasons for these changes. Compared with the protocols, three COSs changed the number of Delphi rounds, eight COSs changed the participants (stakeholder groups), and three COSs changed the consensus definition of the Delphi survey. Only two COSs explained the reason for changing the number of Delphi rounds, and none of the studies explained why the participants changed. For the face-to-face consensus meeting, we found that nine COSs changed the participants and none explained the reasons for these changes. CONCLUSION: Our study found many inconsistencies between protocols and the full-text publications concerning COS development. These inconsistencies related to the included study types, databases searched, Delphi surveys, and face-to-face consensus meetings. As it is necessary to publish protocols before developing COSs, transparency regarding any changes to the methods is needed.

Research Collaboration and Outcome Measures of Interventional Clinical Trial Protocols for COVID-19 in China.

Background: Research collaboration of registered clinical trials for Coronavirus Disease 2019 (COVID-19) remains unclear. This study aimed to analyze research collaboration and distribution of outcome measures in registered interventional clinical trials (ICTs) of COVID-19 conducted in China. Methods: The International Clinical Trials Registry Platform, China Clinical Trials Registry, and Clinicaltrials.gov were searched to obtain COVID-19-registered ICTs up to May 25, 2020. Excel 2016 was used to perform a descriptive statistical analysis of the extracted information. VOSviewer 1.6.14 software was used to generate network maps for provinces and institutions and create density maps for outcomes. Results: A total of 390 ICTs were included, and the number of daily registrations fluctuated greatly. From 29 provinces in China, 430 institutions contributed to the registration of ICTs. The top three productive provinces were Hubei (160/390, 41.03%), Shanghai (60/390, 15.38%), and Beijing (59/390, 15.13%). The top three productive institutions were Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (30/390, 7.69%), Zhongnan Hospital of Wuhan University (18/390, 4.62%), and Wuhan Jinyintan Hospital (18/390, 4.62%). Collaborations between provinces and institutions were not close enough. There were many interventions, but many trials did not provide specific drugs and their dosage and treatment duration. The most frequently used primary outcome was Chest/lung CT (53/390, 13.59%), and the most frequently used secondary outcome was hospital stay (33/390, 8.46%). There was a large difference in the number of outcomes, the expression of some outcomes was not standardized, the measurement time and tools for some outcomes were not clear, and there was a lack of special outcomes for trials of traditional Chinese medicine. Conclusions: Although there were some collaborations between provinces and institutions of the current COVID-19 ICT protocols in China, cooperation between regions should be further strengthened. The identified deficiencies in interventions and outcome measures should be given more attention by future researchers of COVID-19.

[Analysis of traditional Chinese medicine from patent information sharing platform of coronavirus disease 2019 (COVID-19)].

Coronavirus disease 2019(COVID-19) is a newly emerged and highly contagious respiratory disease. Traditional Chinese medicine(TCM) has both systematism theory knowledge and clinical practical value in the prevention and treatment of COVID-19. Therefore, it was particularly important to examine the effect of TCM in the prevention and treatment of COVID-19. The patents of TCM might reflect the latest progression of scientific research. We aimed to provide reference for the prevention and treatment of COVID-19 by extracting and analyzing the TCM patents from the Patent Information Sharing Platform of COVID-19. The antiviral TCM patents were screened and exported from the Patent Information Sharing Platform. VOSviewer 1.6.14 was used to visualize and analyze the network of TCM in these patents. There were total 292 TCM patents, including 52 patents for etiological treatment and 240 patents for symptomatic treatment. Thirty-two provinces and 1 076 inventors were involved, mainly from Beijing, Guangdong and Jiangsu. Overall, there were 356 TCMs, 71 single prescriptions, and 221 compound prescriptions. The patents for treatment of coronavirus mainly focused on the treatment of coronavirus, while the patents for symptomatic treatment mainly focuses on the improvement of respiratory symptoms, such as fever and cough. There were 14 highly frequently used TCMs, including Glycyrrhizae Radix et Rhizoma, Scutellariae Radix, Lonicerae Japonicae Flos, Forsythiae Fructus, Isatidis Radix, Astragali Radix, Menthae Haplocalycis Herba, Gypsum Fibrosum, Houttuyniae Herba, Isatidis Folium, Rhei Radix et Rhizoma, Gardeniae Fructus, Platycodonis Radix, Armeniacae Semen Amarum. The analyzed results of the TCM patents from the patent information sharing platform of COVID-19 were consistent with the Guideline of Diagnosis and Treatment of COVID-19(7th edition), and the combination of TCM in each cluster may also provide future directions for drug compatibility.

Statistical analyses and quality of individual participant data network meta-analyses were suboptimal: a cross-sectional study.

BACKGROUND: Network meta-analyses using individual participant data (IPD-NMAs) have been increasingly used to compare the effects of multiple interventions. Although there have been many studies on statistical methods for IPD-NMAs, it is unclear whether there are statistical defects in published IPD-NMAs and whether the reporting of statistical analyses has improved. This study aimed to investigate statistical methods used and assess the reporting and methodological quality of IPD-NMAs. METHODS: We searched four bibliographic databases to identify published IPD-NMAs. The methodological quality was assessed using AMSTAR-2 and reporting quality assessed based on PRISMA-IPD and PRISMA-NMA. We performed stratified analyses and correlation analyses to explore the factors that might affect quality. RESULTS: We identified 21 IPD-NMAs. Only 23.8% of the included IPD-NMAs reported statistical techniques used for missing participant data, 42.9% assessed the consistency, and none assessed the transitivity. None of the included IPD-NMAs reported sources of funding for trials included, only 9.5% stated pre-registration of protocols, and 28.6% assessed the risk of bias in individual studies. For reporting quality, compliance rates were lower than 50.0% for more than half of the items. Less than 15.0% of the IPD-NMAs reported data integrity, presented the network geometry, or clarified risk of bias across studies. IPD-NMAs with statistical or epidemiological authors often better assessed the inconsistency (P = 0.017). IPD-NMAs with a priori protocol were associated with higher reporting quality in terms of search (P = 0.046), data collection process (P = 0.031), and syntheses of results (P = 0.006). CONCLUSIONS: The reporting of statistical methods and compliance rates of methodological and reporting items of IPD-NMAs were suboptimal. Authors of future IPD-NMAs should address the identified flaws and strictly adhere to methodological and reporting guidelines.