Deep learning for locally advanced nasopharyngeal carcinoma prognostication based on pre- and post-treatment MRI.

PURPOSE: We aimed to predict the prognosis of advanced nasopharyngeal carcinoma (stage Ⅲ-Ⅳa) using Pre- and Post-treatment MR images based on deep learning (DL). METHODS: A total of 206 patients with primary nasopharyngeal carcinoma who were diagnosed and treated at the Renmin Hospital of Wuhan University between June 2012 and January 2018 were retrospectively selected. A rectangular region of interest (ROI), which included the tumor area, surrounding tissues and organs, was delineated on each Pre- and Post-treatment MR image. Two Inception-Resnet-V2 based transfer learning models, named Pre-model and Post-model, were trained with the Pre-treatment images and the Post-treatment images, respectively. In addition, an ensemble learning model based on the Pre-model and Post-models was established. The three established models were evaluated by receiver operating characteristic curve (ROC), confusion matrix, and Harrell's concordance indices (C-index). High-risk-related gradient-weighted class activation mapping (Grad-CAM) images were developed according to the DL models. RESULTS: The Pre-model, Post-model, and ensemble model displayed a C-index of 0.717 (95% CI: 0.639 to 0.795), 0.811 (95% CI: 0.745-0.877), 0.830 (95% CI: 0.767-0.893), and AUC of 0.741 (95% CI: 0.584-0.900), 0.806 (95% CI: 0.670-0.942), and 0.842 (95% CI: 0.718-0.967) for the test cohort, respectively. In comparison with the models, the performance of Post-model was better than the performance of Pre-model, which indicated the importance of Post-treatment images for prognosis prediction. All three DL models performed better than the TNM staging system (0.723, 95% CI: 0.567-0.879). The captured features presented on Grad-CAM images suggested that the areas around the tumor and lymph nodes were related to the prognosis of the tumor. CONCLUSIONS: The three established DL models based on Pre- and Post-treatment MR images have a better performance than TNM staging. Post-treatment MR images are of great significance for prognosis prediction and could contribute to clinical decision-making.

3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system.

Protein delivery systems have been extensively applied in controlled releasing of protein or polypeptides for therapeutic treatment or tissue regeneration. While 3 D printing technology shows great promise in novel dosage form with tailoring dose size and drug release profile, 3 D printable protein delivery system has to face many difficult challenges. In this study, we developed a hybrid suspension combining Eudragit polyacrylate colloid as matrix material and Pluronic polyether hydrogel as diffusion channel for protein release. This hybrid suspension can be 3 D-printed into construct with complex shape and inner structures thanks to its pseudoplastic and thixotropic rheological properties. The protein can be incorporated in hybrid suspension either in its original or nanoparticle capsulated form. The experiment shows that the protein release from construct is a function of drying time, molecular weight (MW) of chitosan, as well as their own structural/diffusional properties. Also, the theoretical derivation suggests polyacrylate matrix tortuosity, chitosan erosion rate as well as hydrogel diffusion coefficient all contributed to the extended duration of release profile. In addition, cytotoxicity test through cell culture confirmed that the construct fabricated from hybrid suspension exhibit relative good bio-compatibility. Finally, heterogeneous constructs with zoned design were fabricated as protein delivery system, which demonstrated the capability of hybrid suspension technique for spatial and temporal release of macromolecular drugs to realize pharmaceutical effectiveness or guild cell organization.

Left Stellate Ganglion Ablation Inhibits Ventricular Arrhythmias through Macrophage Regulation in Canines with Acute Ischemic Stroke.

AIMS: To investigate the potential mechanism of ventricular arrhythmias (VAs) after acute ischemic stroke and explore the effects of left stellate gangling (LSG) ablation on VAs induced by stroke in canines. Materials and Methods: Twenty canines were randomly divided into the sham-operated group (n=6), AS group (n=7) and SGA group (n=7). Cerebral ischemic model was established in the AS group and the SGA group by right acute middle cerebral artery occlusion (MCAO). LSG ablation was performed in the SGA group as soon as MCAO. After 3 days, atrial electrophysiology and neural activity were measured in vivo. The levels of norepinephrine (NE) in plasma and ventricle were detected by ELISA. The levels of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and NF-κB p65 in ventricle were detected by western blotting. The pro-inflammatory polarization of macrophages in ventricle was detected by immunofluorescence. Results: Higher ventricular tachycardia (VT) inducibility and lower ventricular fibrillation threshold (VFT) were observed in the AS group compared with those in the sham-operated group, associated with higher LSG activity and NE levels, increased number of M1 macrophages and secretion of inflammatory cytokines in ventricle (all P<0.001). Compared with the AS group, the SGA group had lower VT inducibility and higher VFT, combined with lower NE levels, and reduced number of M1 macrophages and secretion of inflammatory cytokines in ventricle (all P<0.001). Conclusion: LSG ablation could reduce VAs vulnerability after acute stroke by preventing the macrophages polarization and activation induced by sympathetic hyperactivity.

A brain-stellate ganglion-atrium network regulates atrial fibrillation vulnerability through macrophages in acute stroke.

AIMS: New-onset atrial fibrillation (AF) is frequently observed following acute stroke. The aim of this study was to investigate the effects of the brain-stellate ganglion-atrium network on AF vulnerability in a canine model with acute middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: Twenty-six dogs were randomly divided into the sham-operated group (n = 6), acute stroke (AS) group (n = 7), stellate ganglion ablation (SGA) group (n = 6) and clodronate liposome (CL) group (n = 7). In the sham-operated group, dogs received craniotomy without MCAO. Cerebral ischemic model was established in AS dogs by right MCAO. Right MCAO along with SGA and CL injection into the atrium was performed in SGA and CL dogs, respectively. After 3 days, atrial electrophysiology, neural activity, and the phenotype and function of macrophages in the atrium were studied in all the dogs. KEY FINDINGS: Higher AF inducibility (24.4 ±â€¯4.4% versus 4.4 ±â€¯2.2%, P < 0.05) and AF duration (15.7 ±â€¯3.8 s versus 2.6 ±â€¯1.1 s, P < 0.05) were observed in the AS group compared with the sham-operated group, and were associated with increased left stellate ganglion activity, higher macrophage infiltration and higher levels of inflammatory cytokines in the atrium. SGA or CL injection sharply suppressed AF inducibility (5.5 ±â€¯2.7% versus 24.4 ±â€¯4.4%; 5.3 ±â€¯3.2% versus 24.4 ±â€¯4.4%, both P < 0.05) and AF duration (2.9 ±â€¯1.2 s versus 15.7 ±â€¯3.8 s; 3.6 ±â€¯1.0 s versus 15.7 ±â€¯3.8 s, both P < 0.05) in canines with acute stroke. SIGNIFICANCE: A brain-stellate ganglion-atrium network may increase AF vulnerability through macrophage activation after acute stroke.

Use of serum and urinary soluble sFlt-1 and PLGF in the diagnosis of preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a disorder of pregnancy marked by hypertension and proteinuria with no known treatment aside from pregnancy termination. The pathogenesis of PE is poorly understood, but is thought to originate in the placenta. We assessed the value of measuring serum and urinary soluble deformylase-like tyrosine kinase receptor 1 (sFlt-1), a known target of placental factors, and placental growth factor (PLGF), a key placental signaling molecule, in the diagnosis of PE. METHODS: Eighty patients with PE were classified as either exhibiting mild (44 cases) or severe (36 cases) symptoms of PE. Forty normal pregnant women were selected as controls. Serum and urinary PLGF and sFlt-1 levels, along with the ratio of sFlt-1 to PLGF, were compared across groups. RESULTS: Serum and urinary sFlt-1 and sFlt-1/PLGF ratios in severe PE patients were significantly higher than those in the mild PE group, and measurements from mild PE patients were significantly higher than controls (all P values <0.01). The serum and urinary PLGF levels in severe PE patients were significantly lower than mild PE patients, and mild PE patients had significantly lower PLGF levels than controls (all P values <0.01). As expected, serum sFlt-1 and PLGF levels and ratios were highly correlated with urinary sFlt-1 and PLGF levels and ratios. CONCLUSIONS: The severity of PE was closely correlated with these measurements, suggesting that they may be useful tools in the diagnosis and evaluation of PE.

[Clinical observation of one stage cranioplasty for skull defect with self-cranial bone powder].

OBJECTIVE: To investigate the clinical application of self-cranial bone powder in one stage cranioplasty. METHODS: From October 1999 to December 2002, self-cranial bone powder and medical adhesive were used to repair the skull defect, for one stage cranioplasty, caused by operations on cranium in 128 cases of severe dangerous craniocerebral injury, acute intracranial hematome, sick skull and intracranial tumor. The bone growth was observed by CT or X-ray examination 3-24 months after replantation of cranioplasty. RESULTS: The decompression and cranioplasty were performed simultaneously, the time prolonged 5-10 minutes than that of routine, the appearance of repaired cranial bone was normal, without concavity and convexity. After 12 months of operation, the replanted bone merged with the normal bone completely, with normal appearance. The operation successful rate was 96.1% (123/125) without any complication. Only five cases were not better in growing because of less bone powder, but without cerebral pulse and defective syndrome. All the cases did not need secondary cranioplasty. CONCLUSION: The effect of cranioplasty with self- cranial bone powder effect is good in taking shape. This new method can avoid the traditional secondary cranioplasty for skull defect and complications.