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Mengqiu Zhong,&ast; Hanlin Xiong,&ast; Kebiao Zhang, Shimin Fu Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kebiao Zhang; Shimin Fu, Email zhangkebiao0537@163.com; fsm204472@hospital-cqmu.comBackground: Early in the pandemic, coronavirus disease 2019 (COVID-19) had been reported with significant impact on the stroke care pathway. Meanwhile, the mid/long-term consequence of treatment efficiency and effectiveness of the acute stroke pathway still remains unknown.Methods: A comprehensive retrospective analysis was conducted on the acute stroke care pathway parameters in a stroke unit in Chongqing, Southwest China. A total of 1492 patients were involved in this study, of whom 634 patients (42.5%) were included during the COVID-19 pandemic, 858 patients (57.5%) included during the similar period of 2019. We collected demographic and clinical characteristics, clinical outcome as the treatment efficiency and effectiveness indicators of the acute stroke pathway.Results: Compared to the same period in 2019, there were 2.8% fewer transient ischemic attack (TIA) patients, while 9.9% more acute ischemic stroke patients in 2020. In addition, patients had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores (P = 0.002) and hospital mortality (P = 0.004) during the pandemic. The median door-CT time (P < 0.001) and emergency stay (P < 0.001) of acute stroke were also remarkably increased during the pandemic. The proportion of patients with intravenous thrombolysis (IVT) was significantly lower (P < 0.001), while the mechanical thrombectomy (MET) was remarkably higher (P = 0.042) in the pandemic group. Moreover, the IVT was significantly delayed during the pandemic (door-needle time: P = 0.001).Conclusion: The COVID-19 outbreak did not reduce the willingness of the acute stroke patient to seek medical help. Benefited from adjustments of stroke procedure in response to the COVID-19 pandemic, no significant reduction was observed in the reperfusion success of the acute stroke care pathway. However, more medical resources need to be invested into the acute stroke care pathway to prevent serious consequences of undiagnosed and untreated strokes.Keywords: COVID-19, acute stroke care pathway, intravenous thrombolysis, mechanical thrombectomy

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly

The development of activatable photosensitizers (PSs) is of particular interest for achieving tumor photodynamic therapy (PDT) with minimal side effects. However, the in vivo applications of PSs are limited by complex physiological and biological delivery barriers. Herein, boron dipyrromethene (BDP)-based nanoparticles are developed through the self-assembly of a multifunctional "one-for-all" building block for enhanced tumor penetration and activatable PDT. The nanoparticles show excellent colloidal stability and long circulation lifetime in blood. Once they reach the tumor site, the first-stage size reduction occurs due to the hydrolysis of the Schiff base bond between polyethylene glycol and the cyclic Arg-Gly-Asp peptide in the acidic tumor microenvironment (pH~6.5), facilitating tumor penetration and specific recognition by cancer cells overexpressing integrin ανβ3 receptors. Upon the endocytosis by cancer cells, the second-stage size reduction is triggered by more acidic pH in lysosomes (pH~4.5). Importantly, the protonated diethylamino groups can block photoinduced electron transfer from the amine donor to the excited PSs and accelerate complete disassembly of the nanoparticles into single PS molecule, with the recovery of the fluorescence and photoactivity for efficient PDT. This study presents a smart PS delivery strategy involving acidity-triggered hierarchical disassembly from the nano to molecular scale for precise tumor PDT. National Research Foundation (NRF) This work was supported by the Natural Science Foundation of Zhejiang Province (LY20B020001 and LQ19E020010), the National Natural Science Foundation of China (51902289), and Zhejiang International Science and Technology Cooperation Project (2019C04020). This research is also supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03) and the Singapore Academic Research Fund (RT12/19).

Bladder cancer, with the highest recurrence rate in all malignancy, is a common urologic cancer that arises on the bladder mucosa. Currently, tumor resection followed by intravesical chemotherapy is the primary treatment of bladder cancer, which has limited effectiveness ascribe to short dwell-time of intravesical drugs in bladder. Therefore, there is a need to develop mucoadhesive and sustained drug delivery systems to increase drug residence time for intravesical chemotherapy. In this study, poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of mesoporous silica nanoparticles (MSNPs) through a layer-by-layer grafting method. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. Results demonstrated an increase in the mucoadhesive capacity of PAMAM-modified MSNPs upon an increase in the number of PAMAM amino groups, and the maximum nanoparticle mucoadhesivity was observed after two-generation PAMAM were grafted on the surface of MSNPs. An antineoplastic, doxorubicin, was encapsulated in the mesopores of PAMAM-modified MSNPs, and the drug-loaded nanoparticles can provide a sustained drug release triggered by acidic pH. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy.

Supplemental Digital Content is available in the text, Introduction: Acute renal colic is one of the most common urological emergencies. While previous randomized controlled trials (RCTs) and pairwise meta-analyses only looked at the efficacy of 1 or 2 analgesics. It is not fully understood that the comprehensive ranking of the effectiveness and safeness of analgesics from these published articles. Therefore, this network meta-analysis (NMA) aims to compare and rank the different analgesics for treatment of acute renal colic. Methods and analysis: We will perform a systematic literature search in PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library to identify RCTs of different analgesics for acute renal colic. RCTs assessing active analgesics intervention against active comparator or placebo controls for acute renal colic will be included. We will also screen the reference lists of included studies, previous reviews and meta-analyses to identify other relevant trials. The primary outcomes will be pain variance at 30 minutes, need rescue medicine, complete pain relief or at least 50% pain relief at 30 minutes, and pain relapse within 24 hours. We will also assess secondary outcomes for safeness (side effects: dizziness, vomit, allergic, hypotension, cardiac toxicity, and drug dependence). The risk of bias of included RCTs will be assessed by using the Cochrane Collaboration's tool, and the quality of evidence will be assessed by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. We will perform pairwise meta-analysis and Bayesian NMA to compare the effectiveness and safeness of different analgesic interventions. Results: This NMA will compare and rank the different analgesics for treatment of acute renal colic. Conclusion: This is the first systematic review to use the NMA to comprehensively compare and rank analgesics for relieving pain of acute renal colic in adults based on most important factors deciding the choice of initial analgesia, and the results can provide implications for clinical practice and further research.