Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer.

Due to the limitations of autologous chimeric antigen receptor (CAR)-T cells, alternative sources of cellular immunotherapy, including CAR macrophages, are emerging for solid tumors. Human induced pluripotent stem cells (iPSCs) offer an unlimited source for immune cell generation. Here, we develop human iPSC-derived CAR macrophages targeting prostate stem cell antigen (PSCA) (CAR-iMacs), which express membrane-bound interleukin (IL)-15 and truncated epidermal growth factor receptor (EGFR) for immune cell activation and a suicide switch, respectively. These allogeneic CAR-iMacs exhibit strong antitumor activity against human pancreatic solid tumors in vitro and in vivo, leading to reduced tumor burden and improved survival in a pancreatic cancer mouse model. CAR-iMacs appear safe and do not exhibit signs of cytokine release syndrome or other in vivo toxicities. We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer.

An Innovative method for intraoperative guidance of nasal shape in rhinoplasty: Application of a convenient, sterilizable, patient-specific film model.

BACKGROUNDS: 3D simulation is increasingly used in rhinoplasty. However, during the operation, there is no tool to directly link the 3D simulation results with the intraoperative operation. Doctors rely on 3D simulation results only according to their intuition. Recently, the authors have discovered a simple, low-cost, and practical method for intraoperative assessment: a film model can be made according to the contour of the nose shape in its midsagittal view. The authors aimed to evaluate the effectiveness of the innovative method for intraoperative assessment of nasal shape in rhinoplasty. METHODS: Thirty-nine patients who underwent rhinoplasty for the first time between January 2019 and January 2021 were included in this study. All the patients confirmed ideal nasal shape based on preoperative three-dimensional photography (INOVA 3D-EX). In the guide group, procedures were based on guide of the film model and a picture of 3D simulation, and in the control group, procedures were performed based on the surgeon's intuition and a picture of 3D simulation. RESULTS: There were no statistical differences in basic data between the two groups before operation. Both groups showed a satisfactory correlation. Except for the columellar lobular angle, the ICC of nasal length, nasal depth, dorsum height, columella length, nasofrontal angle, nasorostral angle, and nasolabial angle were all stronger in the guide group than in the control group. CONCLUSION: This study demonstrates the usefulness of the nasal-shaped film model, which is made according to the contour of the nose shape in its midsagittal view. This approach is simple, low-cost, and practical.

The safety and efficacy of mesenchymal stem cell therapy in diabetic lower extremity vascular disease: a meta-analysis and systematic review.

BACKGROUND AIMS: Several studies have shown the efficacy of mesenchymal stem cell (MSC) therapy for lower extremity vascular disease (LEVD) in diabetic patients, but the results are not consistent. Therefore, the authors conducted a meta-analysis of randomized controlled trials (RCTs) to examine the safety and efficacy of MSC therapy in diabetic patients with LEVD. METHODS: Eight available databases were searched in both English and Chinese to identify RCTs comparing MSC therapy-based conventional treatment with conventional treatment alone in diabetic patients with LEVD. Three investigators independently screened the literature, extracted the data and assessed the risk bias. Meta-analysis was performed using RevMan 5.4.1 and Stata 14.0. RESULTS: A total of 10 studies involving 453 patients were included. Compared with conventional treatment only, patients receiving MSC therapy-based conventional treatment had a higher ulcer healing rate, greater number of reduced ulcers and shorter complete healing time. MSC therapy also increased ankle-brachial index and transcutaneous oxygen pressure. In addition, four of the included studies showed that MSC therapy significantly improved the number of new collateral vessels. Moreover, no more adverse events were recorded in the MSC group. CONCLUSIONS: This meta-analysis suggests that MSC therapy promotes ulcer healing in diabetic LEVD patients with ulcers, improves blood supply and has a favorable safety profile. More large and well-designed RCTs with long-term follow-up are still needed to explore the safety and efficacy of MSC therapy in diabetic patients with LEVD.

The Efficacy and Safety of Botulinum Toxin Injections in Preventing Postoperative Scars and Improving Scar Quality: A Systematic Review and Meta-Analysis.

BACKGROUND: Scars exposed on the body surface lead to a large psychological burden on patients. However, no satisfactory scar treatments exist. Botulinum toxin type A is a neurotoxin that has been widely applied in the plastic and cosmetic surgery field. The purpose of this meta-analysis was to assess the efficacy and safety of botulinum toxin in scar management. METHODS: PubMed, the Cochrane Library, EMBASE, MEDLINE, and Web of Science were searched for randomized controlled trials that evaluated the efficacy of botulinum toxin injections in preventing postoperative scars and improving scars quality and were published prior to Dec. 29, 2020. The outcome indicators were the visual analog scale score, Vancouver scar scale score, Stony Brook scar evaluation scales score, scar width, patient self-assessment results, and complications. RESULTS: Seventeen randomized controlled trials with a total of 633 cases were identified in this meta-analysis. The quantitative synthesis results showed that compared with the control group, the botulinum toxin group had a significantly lower VSS score (MD = -0.97, 95%CI = -1.56 to -0.39, p = 0.001), higher VAS score (MD = 1.26, 95%CI = 1.04 to 1.47, p < 0.00001), thinner scar width (MD = -0.25, 95%CI = -0.37 to -0.12, p < 0.0001) and higher patient satisfaction (RR = 3.38 95%CI = 1.45 to 7.89, p = 0.005). There were no significant differences between the two groups in the number of adverse events. CONCLUSIONS: This meta-analysis demonstrated that botulinum toxin injections can significantly improve cosmetic appearance and postoperative scar quality. At the therapeutic dose, no significant complications were observed, indicating that botulinum toxin injections are safe. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .