Microfluidic paper-based analytical devices (μPADs) are a growing class of low-cost chemo/biosensing technologies designed for point-of-use applications. In this article, we describe MTWP (movable-type wax printing), a facile method for the fabrication of μPADs. MTWP is inspired by the Chinese movable-type printing and requires only a hot plate and homemade small iron movable components. It is able to pattern various wax microstructures in paper via a simple adjustment of the number, patterning forms or types of the metal movable components. This inexpensive and versatile method may thus hold great potential for producing wax-patterned μPADs by untrained operators at minimized cost in developing countries. In addition, two novel equipment-free assay methods are further developed to render μPAD measurements straightforward and quantitative. They use the flow-through time of a detection reagent in a three-dimensional paper device and the number of colored detection microzones in a 24-zone paper device as the detection motifs. The timing method is based on the selective wettability change of paper from hydrophilic to hydrophobic that is mediated by enzymatic reactions. The counting method is carried out on the basis of oxidation-reduction reactions of a colored substance, namely iodine. Their utility is demonstrated with quantitative detection of hydrogen peroxide as a model analyte. These methods require only a timer or a cell phone with a timing function and the abilities of seeing color and of counting for quantitative μPAD measurement, thus making them simple, cost-efficient, and useful sensor technologies for a great diversity of point-of-need applications especially in resource-poor settings.
ObjectiveThis study aims to assess the efficacy and safety of penpulimab (a humanized anti-PD-1 IgG1 antibody) with anlotinib in the first-line treatment of Chinese patients with uHCC.MethodsIn this open-label multicenter phase Ib/II trial, patients with histologically or cytologically confirmed uHCC, without previous systemic treatment, aged 18–75 years old, classified as BCLC stage B (not amenable for locoregional therapy) or C, with Child–Pugh score ≤7 and ECOG performance status ≤1 were enrolled. Patients received penpulimab [200 mg intravenous (i.v.) Q3W] and oral anlotinib (8 mg/day, 2 weeks on/1 week off). The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), time to progression (TTP), duration of response (DoR), and overall survival (OS). This trial is registered with ClinicalTrials.gov (NCT04172571).ResultsAt the data cutoff (December 30, 2020), 31 eligible patients had been enrolled and treated with a median follow-up of 14.7 months (range, 1.4–22.1). The ORR was 31.0% (95% CI, 15.3–50.8%), and the DCR was 82.8% (95% CI, 64.2–94.2%). The median PFS and TTP for 31 patients were 8.8 months (95% CI, 4.0–12.3) and 8.8 months (95% CI, 4.0–12.9) respectively. The median OS was not reached; the 12-month OS rate was 69.0% (95% CI, 48.9–82.5%). Only 19.4% (6/31) of patients had grade 3/4 treatment-related adverse events (TRAEs).ConclusionPenpulimab plus anlotinib showed promising anti-tumor activity and a favorable safety profile as first-line treatment of patients with uHCC.
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