Continuous Spatiotemporal Therapy of A Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis.

Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe3+, and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe2+, biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe2+/BV-BR metabolic pathway, further cooperating with released Fe3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs.

Polymersome-stabilized doxorubicin-lipiodol emulsions for high-efficacy chemoembolization therapy.

Transarterial chemoembolization (TACE) with free doxorubicin-lipiodol emulsions (free DOX/L) is a favored clinical treatment for advanced hepatocellular carcinoma (HCC) patients ineligible for radical therapies; however, its inferior colloidal stability not only greatly reduces its tumor retention but also hastens drug release into blood circulation, leading to suboptimal clinical outcomes. Here, we find that disulfide-crosslinked polymersomes carrying doxorubicin (Ps-DOX) form super-stable and homogenous water-in-oil microemulsions with lipiodol (Ps-DOX/L). Ps-DOX/L microemulsions had tunable sizes ranging from 14 to 44 µm depending on the amount of Ps-DOX, were stable over 2 months storage as well as centrifugation, and exhibited nearly zero-order DOX release within 15 days. Of note, Ps-DOX induced 2.3-13.4 fold better inhibitory activity in all tested rat, murine and human liver tumor cells than free DOX likely due to its efficient redox-triggered intracellular drug release. Interestingly, transarterial administration of Ps-DOX/L microemulsions in orthotopic rat N1S1 syngeneic HCC model showed minimal systemic DOX exposure, high and long hepatic DOX retention, complete tumor elimination, effective inhibition of angiogenesis, and depleted adverse effects, significantly outperforming clinically used free DOX/L emulsions. This smart polymersome stabilization of doxorubicin-lipiodol microemulsions provides a novel TACE strategy for advanced tumors.

Efficacy of weekly paclitaxel for the treatment of advanced ovarian cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aims to assess the efficacy and safety of weekly paclitaxel (WP) for the treatment of advanced ovarian cancer (AOC). METHODS: This study will systematically search bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, PSYCINFO, Allied and Complementary Medicine Database, CNKI, WANGFANG, and Chinese Biomedical Literature Database) and other literature sources from inception to the March 1, 2020 without language and publication time limitations. Two authors will independently complete all literature selection, data collection, and study quality evaluation. Any disagreements will be solved by a third author through discussion. We will analyze data by RevMan V.5.3 software. RESULTS: This study will systematically generate a comprehensive summary on the efficacy and safety of WP for the treatment of AOC. CONCLUSION: This study may provide beneficial evidence of WP for the treatment of AOC. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040193.

Effect of melatonin for the management of endometriosis: A protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to explore the effect of melatonin for the management of endometriosis. METHODS: We will search electronic databases (Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) from their inceptions to the February 29, 2020 without language and publication time limitations. The study identification, study quality assessment, and data extraction will be undertaken by two separate researchers. We will also appraise evidence quality of main outcomes by Grading of Recommendations Assessment Development and Evaluation, and statistical analysis performance by RevMan 5.3 Software. RESULTS: This study will summarize up-to-date clinical evidence to investigate the effect of melatonin for the management of endometriosis. CONCLUSION: This study may provide helpful evidence of melatonin for the management of endometriosis. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040093.

Weekly cisplatin for the treatment of patients with ovarian cancer: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Ovarian cancer (OC) is one of the most leading causes of deaths in the Chinese women. The objective of this protocol is to perform a full-scale systematic review on the efficacy of weekly cisplatin (WC) for the treatment of patients with OC. METHODS: Data sources will comprise of PubMed, PsycINFO, Scopus, Opengrey, Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All relevant randomized controlled trials from searched databases will be identified from their inception to the present. A defined search strategy will be implemented along with eligibility criteria. Relevant data will be extracted according to the predefined data collection form. Methodologic quality will be assessed by using Cochrane risk of bias tool; and data pooled and meta-analysis will be conducted by using fixed-effects, or random-effects model with RevMan 5.3 software. RESULTS: This proposed systematic review will evaluate the efficacy of WC for patients with OC. CONCLUSION: The findings of this study may summarize the latest evidence for the WC on OC. ETHICS AND DISSEMINATION: Ethical approval is not required for this study, because it will be based on published studies, and existing sources of literature. The results of this study will be disseminated through peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018120938.

The epidemiology and prognosis of patients with massive burns: A multicenter study of 2483 cases.

OBJECTIVE: Epidemiological features of massively burned patients in China remains unclear. This study was designed to investigate the epidemiological characteristics and evaluate the burn index (BI) and other risk factors associated with the prognosis of massively burned patients. METHODS: Data of patients with ≥30% total body surface area burned admitted in 2014 were retrieved from 106 burn centers in the mainland of China. Information of epidemiological features and the outcome were collected for retrospective analysis. RESULTS: A total of 2483 massively burned patients were included in this study, with a male-to-female ratio of 2.29:1, the mean age of 49.23±16.67 years, mean TBSA of 55.53±21.39% and the mean BI of 39.75±21.59. Scald accounted for 81.07% of the injuries in children, while flame accounted for 66.89% and 74.31% of the injuries in adults and seniors. Approximately 17.76% of the patients were admitted to the local burn center after 6h of injury, and the wound areas of 1154 (46.48%) patients were covered with folk remedies. The mortality was 9.79%, and the area under the receiver operating characteristic (ROC) curve for BI was 0.941 (95% CI, 0.929-0.954). When the value of BI was above a threshold of 29 in the 0-14 years age group, 43.5 in the 15-59 years age group and 35.5 in the 60 years or older age group, the mortality increased significantly. Multivariate logistic regression analyses showed that the odds ratio (OR) of death increased 6% with an increase in the BI of 1.0. Patients older than 60 years, the admission time longer than 6h after-injury (adjusted OR, 1.797; 95% CI, 1.179-2.740; adjusted p<0.001), and patients with a combined inhalation injury (adjusted OR, 6.649; 95% CI, 4.517-9.789; adjusted p<0.000), were at higher risk of death. CONCLUSIONS: There are etiological characteristics of the different age groups that should be considered for prevention. BI can be a reliable index of prognosis in severely burned patients. The results of the study showed that a large BI, elderly age, delayed admission after injury and combined inhalation injury are the main risk factors for extensively burned patients.

Low molecular weight heparin monotherapy for recurrent abortion with antiphospholipid system: A protocol of a systematic review.

BACKGROUND: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS. METHODS: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies. RESULTS: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events. CONCLUSION: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS. DISSEMINATION AND ETHICS: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121064.

Comparison of local infiltration analgesia and sciatic nerve block for pain control after total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to perform a meta-analysis to evaluate the efficiency and safety between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when combined with femoral nerve block (FNB) after total knee arthroplasty (TKA). METHODS: A systematic search was performed in MEDLINE (1966-2017.04), PubMed (1966-2017.04), Embase (1980-2017.04), ScienceDirect (1985-2017.04), and the Cochrane Library. Only high-quality studies were selected. Meta-analysis was performed using Stata 11.0 software. RESULTS: Four randomized controlled trials (RCTs) and two non-randomized controlled trials (non-RCTs), including 273 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of visual analogue scale (VAS) score at 12 h (SMD = -0.303, 95% CI -0.543 to -0.064, P = 0.013), VAS score at 24 h (SMD = -0.395, 95% CI -0.636 to -0.154, P = 0.001), morphine equivalent consumption at 24 h (SMD = -0.395, 95% CI -0.636 to -0.154, P = 0.001), and incidence of nausea (RD = 0.233, 95% CI 0.107 to 0.360, P = 0.000) and vomiting (RD = 0.131, 95% CI 0.025 to 0.237, P = 0.015). CONCLUSION: FNB-combined SNB provides superior pain relief and less morphine consumption within the first 24 h compared FNB-combined LIA in total knee arthroplasty. In addition, there were fewer side effects associated with SNB. Because the sample size and the number of included studies were limited, a multicenter RCT is needed to identify the effects of the two kinds of methods and further work must include range of motion analyses and functional test.

Ru(ii) polypyridyl complex-incorporated and folate-conjugated vehicle for cancer cell imaging and photoinduced inactivation.

Ru(ii) polypyridyl complexes have been expected as promising therapeutic agents against cancer owing to its DNA photocleavage activity. However, the lack of cell selectivity poses a significant obstacle to their practical application. Herein, the strategy combining cell-specific imaging with photoinduced cell death based on [Ru(phen)2(dppz)](2+) has been developed by incorporating [Ru(phen)2(dppz)](2+) into folate-conjugated liposomes. The cells overexpressing folate receptors could specifically recognize this vehicle and be imaged through the luminescence of [Ru(phen)2(dppz)](2+). Thereafter, the delivered [Ru(phen)2(dppz)](2+) interacted with DNA in cells and led to photoinduced cell death. This work provided a possible alternative for cancer diagnosis and therapy.