In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical (CL) homogeneous compartment pharmacodynamic (PD) models and a spatial-temporal (ST), multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmacokinetic curve (AUC) of the drug blood concentration. We find that an CL-model based on a well-mixed blood compartment is sufficient to correctly predict the in vivo toxicity from in vitro data. However, the ST-model that integrates more experimental information requires a change of at least one parameter to obtain the same prediction, indicating that spatial compartmentalization may indeed be an important factor.

Background: Current reconstruction methods of the pelvic ring after extensive resection of tumors involving the sacroiliac joint have a high incidence of failure. We aimed to study the effect of 3D-printed patient-specific implant reconstruction to show that this method is stable and has a low risk of failure.Methods: Between February 2017 and November 2021, six patients with bone tumors involving the sacroiliac joint (Enneking I + IV) who received 3D-printed patient-specific implants for pelvic reconstructive surgery were retrospectively analyzed. Two female and four male patients with a mean age of 41.83 years (range 25–65 years) were included. Two were osteosarcomas, two chondrosarcomas, one malignant fibrous histiocytoma, and one giant cell tumor of bone. For each patient, preoperative osteotomy guides were designed to ensure accurate tumor resection and individualized prostheses were designed to ensure a perfect fit of the bone defect. General, oncologic, and functional outcomes, implant status, and complications were retrospectively analyzed. The Visual Analog Scale (VAS) was used to assess pain and the Musculoskeletal Tumor Society (MSTS) score was used to assess hip function. Osseointegration was assessed by CT.Results: According to the preoperative design, complete resection of the entire tumor and reconstruction with a custom 3D-printed sacroiliac joint implant was completed without perioperative severe complications or deaths. Relatively satisfactory surgical margins were achieved. The mean operative time and intraoperative blood loss were 495 min (420–600 min) and 2533.33 mL (range, 1,200–3,500 mL), respectively. The mean follow-up was 49.83 months (range, 18–75 months). At the last follow-up, all four patients were disease-free, and the two patients who developed lung metastases were alive with tumors. All patients could walk unassisted. The mean VAS was 1.33 (range, 0–2). The mean MSTS score was 25.33 (range, 24–27). CT showed complete osseointegration of the implant to the ilium and sacrum.Conclusion: The 3D-printed custom prosthesis can effectively reconstruct pelvic stability after total sacroiliac joint resection with satisfactory clinical results.

In recent years, hydrogel microsphere has attracted much attention due to its great potential in the field of skin repair. This paper reviewed the recent progress in the preparation strategy of hydrogel microsphere and its application in skin repair. In this review, several preparation methods of hydrogel microsphere were summarized in detail. In addition, the related research progress of hydrogel microspheres for skin repair was reviewed, and focused on the application of bioactive microspheres, antibacterial microspheres, hemostatic microspheres, and hydrogel microspheres as delivery platforms (hydrogel microspheres as a microcarrier of drugs, bioactive factors, or cells) in the field of skin repair. Finally, the limitations and future prospects of the development of hydrogel microspheres and its application in the field of skin repair were presented. It is hoped that this review can provide a valuable reference for the development of the preparation strategy of hydrogel microspheres and promote the application of hydrogel microspheres in skin repair.

Purpose: To analyze and compare sensitive in vivo characteristics for screening early keratoconus.Methods: This multicenter, case-control study included 712 eyes, after matching for age and biomechanically corrected intraocular pressure, from three clinics in different cities. The keratoconus (n = 288), early keratoconus (n = 91), and normal cornea (n = 333) groups included eyes diagnosed with bilateral keratoconus, fellow eyes with relatively normal topography with unilateral keratoconus, and normal eyes before refractive surgery, respectively. After adjusting for central corneal thickness, differences in vivo characteristics were analyzed among the three groups. The in vivo characteristics were measured by Pentacam and Corvis ST. Fifty-four indices were evaluated to screen for a sensitive index for the detection of early keratoconus.Results: Significant differences were observed in 26 of the 36 corneal biomechanical indeces between the early keratoconus and normal corneas. The area under the receiver operating characteristic curve of tomographic and biomechanical index, Belin/Ambrósio deviation, and Da in differentiating keratoconus from normal cornea was 1.000. Among the top five indeces of the area under the receiver operating characteristic curve for detecting early keratoconus, the corneal biomechanical-related index accounted for 80% (4/5), including A1 dArc length, highest concavity radius, A2 time, and tomographic and biomechanical index, of which the area under the receiver operating characteristic curve of A1 dArc length was 0.901.Conclusion: A1 dArc length and several corneal biomechanical indices are highly sensitive for the detection of early keratoconus, even in the absence of topographic abnormalities. Ophthalmologists should focus on the clinical application of corneal biomechanics and combine corneal tomography for the timely and accurate detection of early keratoconus.

In the past few decades, great progress has been made in the field of nanomaterials against bacterial infection. However, with the widespread emergence of drug-resistant bacteria, people try their best to explore and develop new antibacterial strategies to fight bacteria without obtaining or increasing drug resistance. Recently, multi-mode synergistic therapy has been considered as an effective scheme for the treatment of bacterial infections, especially the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) with controllable, non-invasive, small side effects and broad-spectrum antibacterial characteristics. It can not only improve the efficiency of antibiotics, but also do not promote antibiotic resistance. Therefore, multifunctional nanomaterials which combine the advantages of PTT and PDT are more and more used in the treatment of bacterial infections. However, there is still a lack of a comprehensive review of the synergistic effect of PTT and PDT in anti-infection. This review first focuses on the synthesis of synergistic photothermal/photodynamic nanomaterials and discusses the ways and challenges of photothermal/photodynamic synergism, as well as the future research direction of photothermal/photodynamic synergistic antibacterial nanomaterials.