Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene.

Millirobots must have low cost, efficient locomotion, and the ability to track target trajectories precisely if they are to be widely deployed. With current materials and fabrication methods, achieving all of these features in one millirobot remains difficult. We develop a series of graphene-based helical millirobots by introducing asymmetric light pattern distortion to a laser-induced polymer-to-graphene conversion process; this distortion resulted in the spontaneous twisting and peeling off of graphene sheets from the polymer substrate. The lightweight nature of graphene in combine with the laser-induced porous microstructure provides a millirobot scaffold with a low density and high surface hydrophobicity. Magnetically driven nickel-coated graphene-based helical millirobots with rapid locomotion, excellent trajectory tracking, and precise drug delivery ability were fabricated from the scaffold. Importantly, such high-performance millirobots are fabricated at a speed of 77 scaffolds per second, demonstrating their potential in high-throughput and large-scale production. By using drug delivery for gastric cancer treatment as an example, we demonstrate the advantages of the graphene-based helical millirobots in terms of their long-distance locomotion and drug transport in a physiological environment. This study demonstrates the potential of the graphene-based helical millirobots to meet performance, versatility, scalability, and cost-effectiveness requirements simultaneously.

Simple transanal total mesorectal resection versus laparoscopic transabdominal total mesorectal resection for the treatment of low rectal cancer: a single-center retrospective case-control study.

Aim: To evaluate the efficacy and safety of simple TaTNE in the treatment of low rectal cancer compared with laparoscopic transabdominal TME. Methods: We collected patients with low rectal cancer admitted to our hospital between January 2019 and November 2021 who received simple TaTME or laparoscopic transabdominal TME. The main outcome was the integrity of the TME specimen. Secondary outcomes were the number of lymph nodes dissected, intraoperative blood loss, operative time, surgical conversion rate, Specimen resection length, circumferential margin (CRM), and distal resection margin (DRM), complication rate. In addition, the Wexner score and LARS score of fecal incontinence were performed in postoperative follow-up. Results: Pathological tissues were successfully resected in all patients. all circumferential margins of the specimen were negative. Specimen resection length was not statistically significant (9.94 ± 2.85 vs. 8.90 ± 2.49, P > 0.05). The incidence of postoperative complications in group A (n = 0) was significantly lower than that in group B (n = 3) (P > 0.05). There was no significant difference in operation time between group A and group B (296 ± 60.36 vs. 305 ± 58.28, P > 0.05). Among the patients with follow-up time less than 1 year, there was no significant difference in Wexner score and LARS score between group A and group B (P > 0.05). However, in patients who were followed up for more than 1 year, the Wexner score in group A (9.25 ± 2.73) was significantly lower than that in group B (17.36 ± 10.95) and was statistically significant (P < 0.05). Conclusion: For radical resection of low rectal cancer, Simple TaTME resection may be as safe and effective as laparoscopic transabdominal TME, and the long-term prognosis may be better.

A phase I study of FCN-411, a pan-HER inhibitor, in EGFR-mutated advanced NSCLC after progression on EGFR tyrosine kinase inhibitors.

BACKGROUND: There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs. METHODS: We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4, in patients with EGFR-mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB-IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled. In the dose-escalation phase, patients received 4 mg, 8 mg, 12 mg, and 16 mg FCN-411 once daily until the maximum tolerated dose (MTD). In the dose-expansion phase, patients received FCN-411 at the recommended phase II dose (RP2D) continuously in 21-day cycles. The primary endpoints were safety, tolerability, MTD, and RP2D. RESULTS: From July 23, 2018 to September 29, 2020, 77 patients were enrolled, including 30 with EGFR T790M mutation in tumor tissues. The cut-off date was February 1, 2021. No dose-limiting toxicities were observed. The most common grade ≥ 3 treatment-emergent adverse events among all patients were diarrhea (8; 10.4%) and dermatitis acneiform (7; 9.1%). Ten of 67 evaluable patients achieved confirmed partial response, with an objective response rate (ORR) of 14.9% (95% confidence interval [CI], 8.3-24.0); the ORR was 33.3%, 14.0%, 0, and 25.0% at 4 mg, 8 mg, 12 mg, and 16 mg, respectively. Besides, the ORR in patients without and with EGFR T790M mutation was 20.5% and 7.4%, respectively. Moreover, 39 patients achieved stable disease across all doses, and the disease control rate was 73.1% (95% CI, 60.9-83.2). Median progression-free survival was 4.1 (95% CI, 2.9-5.3) months. Median duration of response and overall survival have not been reached. CONCLUSIONS: FCN-411 was well tolerated and demonstrated preliminary antitumor activity in patients with EGFR-mutated NSCLC after progression on EGFR-TKIs, especially in those without EGFR T790M mutation. The RP2D was defined as 8 mg once daily. Future studies are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420079.

A phantom study comparing low-dose CT physical image quality from five different CT scanners.

BACKGROUND: To systematically evaluate the physical image quality of low-dose computed tomography (LDCT) on CT scanners from 5 different manufacturers using a phantom model. METHODS: CT images derived from a Catphan 500 phantom were acquired using manufacturer-specific iterative reconstruction (IR) algorithms and deep learning image reconstruction (DLIR) on CT scanners from 5 different manufacturers and compared using filtered back projection with 2 radiation doses of 0.25 and 0.75 mGy. Image high-contrast spatial resolution and image noise were objectively characterized by modulation transfer function (MTF) and noise power spectrum (NPS). Image high-contrast spatial resolution and image low-contrast detectability were compared directly by visual evaluation. CT number linearity and image uniformity were compared with intergroup differences using one-way analysis of variance (ANOVA). RESULTS: The CT number linearity of 4 insert materials were as follows: acrylic (95% CI: 120.35 to 121.27; P=0.134), low-density polyethylene (95% CI: -98.43 to -97.43; P=0.070), air (95% CI: -996.16 to -994.51; P=0.018), and Teflon (95% CI: 984.40 to 986.87; P=0.883). The image uniformity values of GE Healthcare (95% CI: 3.24 to 3.83; P=0.138), Philips (95% CI: 2.62 to 3.70; P=0.299), Siemens (95% CI: 2.10 to 3.59; P=0.054), Minfound (95% CI: 2.35 to 3.65; P=0.589), and Neusoft (95% CI: 2.63 to 3.37; P=0.900) were evaluated and found to be within ±4 Hounsfield units (HU), with a range of 0.99-2.76 HU for standard deviations. There was no statistically significant difference in CT number linearity and image uniformity across the 5 CT scanners under different radiation doses with IR and DLIR algorithms (P>0.05). The resolution level at 10% MTF was 6.98 line-pairs-per-centimeter (lp/cm) on average, which was similar to the subjective evaluation results (mostly up to 7 lp/cm). DLIR at all 3 levels had the highest 50% MTF values among all reconstruction algorithms. For image low-contrast detectability, the minimum diameter of distinguishable contrast holes reached 4 mm at a 0.5% resolution. Increasing the radiation dose and IR strength reduced the image noise and NPS curve peak frequency while improving image low-contrast detectability. CONCLUSIONS: This study demonstrated that the image quality of CT scanners from 5 different manufacturers in LDCT is comparable and that the CT number linearity is unbiased and can contribute to accurate bone mineral density quantification.

Evaluation on Short-Term Therapeutic Effect of 2 Porphyrin Photosensitizer-Mediated Photodynamic Therapy for Esophageal Cancer.

PURPOSE: To analyze and study the short-term therapeutic effects and main adverse effects of 2 Porphyrin photosensitizer-mediated photodynamic therapy for esophageal cancer. METHODS: We apply the hematoporphyrin derivative and hematoporphyrin injection produced by different manufacturers at different periods as photosensitizers in therapy of 79 esophageal cancer cases, with the administration dosage of 5 mg/kg and intravenous drip 24 hours before irradiation. We apply the gold vapor laser and semiconductor laser, respectively, as treatment light source, with the power density of 100 to 300 mW/cm2 and energy density of 100 to 300 J/cm2. After treatment for 1 to 4 sessions, we evaluate the short-term therapeutic effects as complete response, partial response, minor response, or no change, and then make comparative study on therapeutic effects and adverse effects. RESULTS: There were 47 patients in hematoporphyrin derivative group, including 3 (6.4%) patients with complete response, 31 (66.0%) patients with partial response, 10 (21.3%) patients with minor response, and 3 (6.4%) patients with no change. The dysphagia score was reduced from 2.53 (1.16) before treatment to 1.32 (1.20; P < .01) after treatment. There were 32 patients in the hematoporphyrin injection group, including 3 (9.4%) patients with complete response, 19 (59.4%) patients with partial response, 6 (18.8%) patients with minor response, and 4 (12.5%) patients with no change. The dysphagia score was reduced from 2.41 (1.13) before treatment to 1.18 (0.99; P < .01) after treatment. The dysphagia scores of 2 groups after treatment were significantly reduced compared to those before treatment. Both groups did not display serious adverse effect. CONCLUSIONS: Two porphyrin photosensitizers in treatment of esophageal cancer at different clinical stages all had good effect with similar therapeutic effect, mild adverse effect, and good tolerance, which implies it is a preferable palliative therapy means.

Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a light-activated local treatment modality that is under intensive preclinical and clinical investigations for cancer. To enhance the treatment efficiency of phototherapy and reduce the light-associated side effects, it is highly desirable to improve drug accumulation and precision guided phototherapy for efficient conversion of the absorbed light energy to reactive oxygen species (ROS) and local hyperthermia. In the present study, a programmed assembly strategy was developed for the preparation of human serum albumin (HSA)-indocyanine green (ICG) nanoparticles (HSA-ICG NPs) by intermolecular disulfide conjugations. This study indicated that HSA-ICG NPs had a high accumulation with tumor-to-normal tissue ratio of 36.12±5.12 at 24 h and a long-term retention with more than 7 days in 4T1 tumor-bearing mice, where the tumor and its margin, normal tissue were clearly identified via ICG-based in vivo near-infrared (NIR) fluorescence and photoacoustic dual-modal imaging and spectrum-resolved technology. Meanwhile, HSA-ICG NPs efficiently induced ROS and local hyperthermia simultaneously for synergetic PDT/PTT treatments under a single NIR laser irradiation. After an intravenous injection of HSA-ICG NPs followed by imaging-guided precision phototherapy (808 nm, 0.8 W/cm2 for 5 min), the tumor was completely suppressed, no tumor recurrence and treatments-induced toxicity were observed. The results suggest that HSA-ICG NPs generated by programmed assembly as smart theranostic nanoplatforms are highly potential for imaging-guided cancer phototherapy with PDT/PTT synergistic effects.

Predictive biomarkers for the efficacy of cetuximab combined with cisplatin and capecitabine in advanced gastric or esophagogastric junction adenocarcinoma: a prospective multicenter phase 2 trial.

Cetuximab presents a potential therapy for gastric or esophagogastric junction adenocarcinoma. We aim to evaluate the predictive value of potential biomarkers of cetuximab efficacy. In this prospective phase 2 trial (NCT00477711), we enrolled untreated 47 patients with un-resectable or metastatic gastric or esophagogastric junction adenocarcinoma from seven sites in China. Patients with histologically confirmed adenocarcinoma were given cisplatin (80 mg/m2, triweekly), capecitabine (2,000 mg/m2, triweekly for 2 weeks), and cetuximab weekly (400 mg/m2 at first infusion and 250 mg/m2 subsequently). Sample size was calculated using Simon's two-stage design. The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity, and predictive biomarkers. The ORR was 53.2%, median PFS 5.2 months, and OS 10.8 months. The most frequent toxicities included neutropenia (25.0%), nausea/vomiting (11.5%), and rash/desquamation (9.6%). Patients with grade 2-4 rash achieved a significantly better ORR, longer PFS, and OS than those with grade 0-1 rash. Seven patients (15.9%) with epidermal growth factor receptor (EGFR) strong expression (3+) showed great tumor shrinkage, longer PFS (7.1 months), and OS (16.6 months). EGFR gene amplification was detected in four patients (8.5%), all of whom responded well. Compared to patients with lower levels of transforming growth factor-alpha (TGF-α), those with high levels showed better response and longer PFS (6.0 vs 2.7 months, p=0.001) and OS (12.9 vs 7.0 months, p=0.001). C+XP was well tolerated and effective for advanced gastric or esophagogastric junction adenocarcinoma as first-line therapy. Severity of skin rash and TGF-α level correlated with efficacy, and EGFR overexpression might predict cetuximab efficacy.