Tislelizumab and radiation therapy in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type: a phase II study protocol.

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).

Triclosan induces liver injury in long-life exposed mice via activation of TLR4/NF-κB/NLRP3 pathway.

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Convolutional neural network based anatomical site identification for laryngoscopy quality control: A multicenter study.

OBJECTIVES: Video laryngoscopy is an important diagnostic tool for head and neck cancers. The artificial intelligence (AI) system has been shown to monitor blind spots during esophagogastroduodenoscopy. This study aimed to test the performance of AI-driven intelligent laryngoscopy monitoring assistant (ILMA) for landmark anatomical sites identification on laryngoscopic images and videos based on a convolutional neural network (CNN). MATERIALS AND METHODS: The laryngoscopic images taken from January to December 2018 were retrospectively collected, and ILMA was developed using the CNN model of Inception-ResNet-v2 + Squeeze-and-Excitation Networks (SENet). A total of 16,000 laryngoscopic images were used for training. These were assigned to 20 landmark anatomical sites covering six major head and neck regions. In addition, the performance of ILMA in identifying anatomical sites was validated using 4000 laryngoscopic images and 25 videos provided by five other tertiary hospitals. RESULTS: ILMA identified the 20 anatomical sites on the laryngoscopic images with a total accuracy of 97.60 %, and the average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100 %, 99.87 %, 97.65 %, and 99.87 %, respectively. In addition, multicenter clinical verification displayed that the accuracy of ILMA in identifying the 20 targeted anatomical sites in 25 laryngoscopic videos from five hospitals was ≥95 %. CONCLUSION: The proposed CNN-based ILMA model can rapidly and accurately identify the anatomical sites on laryngoscopic images. The model can reflect the coverage of anatomical regions of the head and neck by laryngoscopy, showing application potential in improving the quality of laryngoscopy.

Combined Plate and Long Screw Fixation of Transverse Condylar Head Fractures.

We describe a method of fixing transverse condylar head fractures using a combination of a plate and long screw fixation. In the technical procedure, a 4-hole mini-plate was placed on the lateral side of the condylar head and the condylar stump after the fracture reduction. The first hole was drilled in the lateral side of the condylar head, and one 9 mm mini-screw was inserted, a second hole drilled from the lateral side of the condyle stump through the medial pole of the condylar head and a 16 mm screw was inserted in an oblique direction from inferior to superior, then 2 more 9 mm mini-screws were inserted just below the long one to complete the procedure. This technique showed excellent results in both short and long-term stability of and healing of the fracture. Furthermore, it is more standardized, reproducible, and less technically demanding.

ROS-NLRP3 signaling pathway induces sterile inflammation after thulium laser resection of the prostate.

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1ß and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1ß, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

Role of EZH2-mediated H3K27me3 in placental ADAM12-S expression: implications for fetoplacental growth.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2)-mediated histone 3 lysine 27 trimethylation (H3K27me3) is a transcription silencing mark, which is indispensable for cell lineage specification at the early blastocyst stage. This epigenetic repression is maintained in placental cytotrophoblasts but is lifted when cytotrophoblasts differentiate into syncytiotrophoblasts. However, the physiological impact of this lift remains elusive. Here, we investigated whether lifting EZH2-mediated H3K27me3 during syncytialization upregulates the expression of a short secretory isoform of a disintegrin and metalloprotease 12 (ADAM12-S), a well-recognized placenta-derived protease that cleaves insulin-like growth factor binding protein 3 to increase insulin-like growth factor (IGF) bioavailability for the stimulation of fetoplacental growth. The transcription factor and the upstream signal involved were also explored. METHODS: Human placenta tissue and cultured primary human placental cytotrophoblasts were utilized to investigate the role of EZH2-mediated H3K27me3 in ADAM12-S expression and the associated transcription factor and upstream signal during syncytialization. A mouse model was used to examine whether inhibition of EZH2-mediated H3K27me3 regulates placental ADAM12-S expression and fetoplacental growth. RESULTS: EZH2 and ADAM12 are distributed primarily in villous cytotrophoblasts and syncytiotrophoblasts, respectively. Increased ADAM12-S expression, decreased EZH2 expression, and decreased EZH2/H3K27me3 enrichment at the ADAM12 promoter were observed during syncytialization. Knock-down of EZH2 further increased ADAM12-S expression in trophoblasts. Syncytialization was also accompanied by increased STAT5B expression and phosphorylation as well as its enrichment at the ADAM12 promoter. Knock-down of STAT5B attenuated ADAM12-S expression during syncytialization. Epidermal growth factor (EGF) was capable of inducing ADAM12-S expression via stimulation of STAT5B expression and phosphorylation during syncytialization. Mouse studies revealed that administration of an EZH2 inhibitor significantly increased ADAM12-S levels in maternal blood and fetoplacental weights along with decreased H3K27me3 abundance and increased ADAM12-S expression in the placenta. CONCLUSIONS: Lifting EZH2-mediated H3K27me3 increases ADAM12-S expression during syncytialization with the participation of EGF-activated STAT5B, which may lead to elevation of ADAM12-S level in maternal blood resulting in increased IGF bioavailability for the stimulation of fetoplacental growth in pregnancy. Our studies suggest that the role of EZH2-mediated H3K27me3 may switch from cell lineage specification at the early blastocyst stage to regulation of fetoplacental growth in later gestation.

Cell death-inducing DFFA-like effector C/CIDEC gene silencing alleviates diabetic cardiomyopathy via upregulating AMPKa phosphorylation.

Cell death-inducing DFFA-like effector C (CIDEC) is responsible for metabolic disturbance and insulin resistance, which are considered to be important triggers in the development of diabetic cardiomyopathy (DCM). To investigate whether CIDEC plays a critical role in DCM, DCM rat model was induced by a high-fat diet and a single injection of low-dose streptozotocin (27.5 mg/kg). DCM rats showed severe metabolic disturbance, insulin resistance, myocardial hypertrophy, interstitial fibrosis, ectopic lipid deposition, inflammation and cardiac dysfunction, accompanied by CIDEC elevation. With CIDEC gene silencing, the above pathophysiological characteristics were significantly ameliorated accompanied by significant improvements in cardiac function in DCM rats. Enhanced AMP-activated protein kinase (AMPK) α activation was involved in the underlying pathophysiological molecular mechanisms. To further explore the underlying mechanisms that CIDEC facilitated collagen syntheses in vitro, insulin-resistant cardiac fibroblast (CF) model was induced by high glucose (15.5 mmol/L) and high insulin (104  µU/mL). We observed that insulin-resistant stimulation dramatically raised CIDEC expression and promoted CIDEC nuclear translocation in CFs. Meanwhile, AMPKα2 was observed to distribute almost completely inside CF nucleus. The results further proved that CIDEC biochemically interacted and co-localized with AMPKα2 rather than AMPKα1 in CF nucleus, which provided a novel mechanism of CIDEC in promoting collagen syntheses. This study suggested that CIDEC gene silencing alleviates DCM via AMPKα signaling both in vivo and in vitro, implicating CIDEC may be a promising target for treatment of human DCM.

Monitoring malignant T-cell clones by direct TCR expression assay in patients with leukemic cutaneous T-cell lymphoma during extracorporeal photopheresis.

BACKGROUND/PURPOSE: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vß usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients. METHODS: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) (n = 15) and during therapy at 3 months and 6 months (n = 12) were used for DTEA, with customized probes for 45 TCR-Vα and 46 TCR-Vß family members. RESULTS: At baseline, DTEA detected TCR-Vß clones in all 15 patients (100%) compared to flow cytometry that detected TCR-Vß clones in 9 of 13 patients (69.2%). In addition to predominant TCR-Vß clones, DTEA also detected additional TCR-Vß clones in 8 of 15 patients (53.3%). Furthermore, DTEA simultaneously identified clonal TCR-Vα usages, which allowed us to pair TCR-Vα and TCRVß usages by malignant T-cells and identify diversified clonotypes. Changes in the relative frequencies of clonal TCR-Vß and TCRVα usages over therapy were consistent with patients' clinical responses. CONCLUSIONS: Our results indicate that DTEA can effectively assess malignant T-cell clones by detecting clonal TCR-Vα and TCR-Vß usages. By providing a global view of TCR repertoires, DTEA may also help us understand the origin(s) of malignant T-cells and pathogenesis of CTCL.

Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance.

WHAT IS KNOWN AND OBJECTIVE: Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated. METHODS: Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters. RESULTS: The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 h-1 , 15.4 L/h, and 322 L, respectively. Sex and concomitant valproate (VPA) were included as significant predictors of olanzapine clearance, which was described by the following equation: CL/F = 15.4 × (1 + 0.546 × SEX) × (1 + 0.264 × VPA). Results of Monte-Carlo simulation suggested that male paediatric patients with concomitant VPA were advised to take no less than 15 mg per day of olanzapine orally, and in female paediatric patients with concomitant VPA, a dosing regimen of 10 mg may be sufficient to achieve the therapeutic range of olanzapine. WHAT IS NEW AND CONCLUSION: Our results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.

The clinical and prognostic factors for biliary neuroendocrine neoplasm: a study based on the SEER database.

BACKGROUND: In this study, we aimed at elucidating the postoperative survival and prognostic factors in patients with biliary neuroendocrine neoplasm (NEN). METHODS: Cases of biliary system NEN and adenocarcinoma from 1975 to 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A propensity score matching (PSM) method was used to adjust baseline differences in clinicopathological characteristics in our analysis. The Kaplan-Meier analysis was carried out for survival analysis. RESULTS: A total of 233 patients with biliary system NEN were enrolled in this study, of which 119 patients' lesions located in gallbladder, while the others' located in bile duct. The postoperative overall survival of bile duct NEN is significantly longer than that of gallbladder NEN (P < 0.001). For gallbladder NENs, surgery method (P = 0.020) and lymph node metastasis (P = 0.018) were identified as independent prognostic factors. In terms of ampulla of vater (AOV) NENs, age (P = 0.017) and lymph node metastasis (P = 0.006) were identified as independent prognostic factors, while grade (P = 0.002) and lymph node metastasis (P = 0.036) were identified as independent prognostic factors for extrahepatic bile duct (EBD) NENs. PSM analysis indicated that patients with biliary duct NENs have a better postoperative prognosis than biliary duct adenocarcinoma. CONCLUSIONS: Patients with NEN have better overall survival than patients with adenocarcinoma. Gallbladder NEN has an adverse prognosis than that of biliary tract NEN. The pathological subtype, differentiation, lymph node metastasis, surgery method, and lymph node resection could affect the postoperative prognosis of the gallbladder and biliary tract NEN.

Foot and ankle reconstruction using the lateral supramalleolar flap versus the anterolateral thigh flap in the elderly: A comparative study.

The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around the foot and ankle with anterolateral thigh (ALT) flap or lateral supramalleolar (LSM) flap and attempt to provide an optimal strategy for elderly patients. A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from October of 2010 and October of 2020 was performed. Based on the flap types, the patients were divided into two groups: ALT flap group (n = 50) and LSM flap group (n = 46). Outcomes were assessed according to the flap survival rate, early complications, general complications, late complications, cosmetic appearance, functional outcomes and Vancouver Scar Scale (VSS). We found that there was no difference in average age, gender, aetiology, size of the defect, debridement times between the two groups; however, a significant difference in operation time, hospitalisation time and cost were noted between them. What's more, the early flap complications between them were not significantly different. The LSM flap group showed less general complications, less flap bulky and lower cosmetic appearance. Moreover, the functional evaluation and VSS seem similar (P > .05). Thus, The ALT flap and LSM flap are both flaps available for foot and ankle reconstruction in elderly patients. However, the LSM flap offers short operation time, short hospitalisation time, and less cost with a lower frequency of postoperative complications. Thus, we advocate the LSM flap for the reconstruction of moderate-size defects of the foot and ankle region in elderly patients.

Single-cell analysis reveals the purification and maturation effects of glucose starvation in hiPSC-CMs.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) play a critical role in most translational and clinical applications. Although glucose starvation (GS) has been evaluated during cellular purification, there has been no comprehensive evaluation of the transcriptional heterogeneity of these cells. Here, we applied GS for 3 days starting at day 10 of differentiation, and then, harvested hiPSC-CMs at day 20 for single-cell RNA sequencing (scRNA-seq). We found that GS dramatically reduced the proportion of non-cardiomyocytes cells and increased the number of late-stage cardiomyocytes. We also recorded an increase in the expression of MYH6, MYH7, ACTN2, TNNT2, and several other genes associated with the structural and functional maturation of cardiomyocytes. Further analysis indicated that these changes were focused on the signaling pathways involved in the regulation of the actin cytoskeleton, cardiac muscle development, and cardiac muscle contraction. Finally, pseudotime analysis revealed that GS hiPSC-CMs developed in a more mature direction. Together, these results suggest that GS treatment improves the purity and maturation of hiPSC-CMs, which should increase the feasibility of hiPSC-CMs applications.

Clinical correlation of cadherin-17 marker with advanced tumor stages and poor prognosis of cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: In this retrospective study, we examined the CA17 tissue expression and analyzed its clinical significance in cholangiocarcinoma (CCA). MATERIALS AND METHODS: Immunohistochemistry was performed to assess CA17 expression on tissue microarrays in a training cohort enrolling 120 CCA patients and a validation cohort comprising 60 CCA patients. Image pro plus was applied to score the staining intensity and expression level of CA17 marker. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of CA17. RESULTS: CA17 cancer biomarker over-expression was significantly observed in CCA compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis. Meanwhile, patients with high expression of CA17 correlated with worse postoperative overall survival (OS) and recurrence-free survival. Besides, multivariate analysis identified that CA17 expression was an independent prognostic factor for cholangiocarcinoma patients, which indicated that the CA17 could be more efficient than serum CA19-9 in predicting the OS of CCA patients. Notably, the nomogram integrating CA17 expression had better prognostic performance as compared with current TNM staging systems. CONCLUSION: CA17 was an independent adverse prognostic factor for CCA patients' survival, which may serve as a promising prognostic biomarker for CCA patients.

An electrochemical aptasensor for the milk allergen ß-lactoglobulin detection based on a target-induced nicking site reconstruction strategy.

Food allergy is an immune system reaction to a particular food, milk being the most common one. ß-Lactoglobulin (ß-Lg) is the main ingredient of milk protein and the main cause of infant milk allergy. On such an occasion, the determination of ß-Lg is very important and the electrochemical sensors are a good alternative for this purpose since they are sensitive, selective and inexpensive. In this work, an electrochemical aptasensor was fabricated for the quantitative detection of ß-Lg in hypoallergenic formula (HF) milk. A tri-functional hairpin (HP) was designed, which was composed of an aptamer sequence, a nicking site and a DNA sequence (T1). In the absence of ß-Lg, the aptamer part hybridized with T1 to form a stable stem-loop structure. However, in the presence of ß-Lg, the capture of the aptamer sequence towards ß-Lg caused the reconstruction of HP and thus the nicking sites were exposed. Then, the nicking enzyme was activated and T1 could be released, which bound with the end of the hairpin 1-methylene blue (HP1-MB)/HP2-MB conjugation on the Au nanoparticle (AuNP) modified electrode surface. Thus, the insulating property of the electrode was enhanced and the current response of MB decreased, which built the quantitative basis for ß-Lg detection. In this way, the proposed aptasensor exhibited a wide linear range of 0.01-100 ng mL-1 and a low detection limit of 5.7 pg mL-1. This aptasensor also displayed high selectivity, reproducibility and stability, and became a promising platform for ß-Lg detection in real food samples.

Global and regional cardiac dysfunction quantified by 18F-FDG PET scans can predict ventricular arrhythmia in patients with implantable cardioverter defibrillator.

BACKGROUND: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. METHODS: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. RESULTS: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). CONCLUSION: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

Magnolol inhibits sodium currents in freshly isolated mouse dorsal root ganglion neurons.

The voltage-gated sodium channel (VGSC) currents in dorsal root ganglion (DRG) neurons contain mainly TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents. Magnolol (Mag), a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, has been well documented to exhibit analgesic effects, but its mechanism is not yet fully understood. The aim of the present study was to investigate whether the antinociceptive effects of Mag is through inhibition of Na+ currents. Na+ currents in freshly isolated mouse DRG neurons were recorded with the whole cell patch clamp technique. Results showed that Mag inhibited TTX-S and TTX-R Na+ currents in a concentration-dependent manner. The IC50 values for block of TTX-S and TTX-R Na+ currents were 9.4 and 7.0 µmol/L, respectively. Therefore, TTX-R Na+ current was more susceptible to Mag than TTX-S Na+ current. For TTX-S Na+ channel, 10 µmol/L Mag shifted the steady state inactivation curve toward more negative by 9.8 mV, without affecting the activation curve. For TTX-R Na+ channel, 7 µmol/L Mag shifted the steady state activation and inactivation curves toward more positive and negative potentials by 6.5 and 11.7 mV, respectively. In addition, Mag significantly postponed recovery of TTX-S and TTX-R Na+ currents from inactivation, and produced frequency dependent blocks of both subtypes of Na+ currents. These results suggest that the inhibitory effects of Mag on Na+ channels may contribute to its analgesic effect.

Differentiation of pulmonary sclerosing pneumocytoma from solid malignant pulmonary nodules by radiomic analysis on multiphasic CT.

PURPOSE: To investigate the diagnostic value and feasibility of radiomics-based texture analysis in differentiating pulmonary sclerosing pneumocytoma (PSP) from solid malignant pulmonary nodules (SMPN) on single- and three-phase computed tomography (CT) images. MATERIALS AND METHODS: A total of 25 PSP patients and 35 SMPN patients with pathologically confirmed results were retrospectively included in this study. For each patient, the tumor regions were manually labeled in images acquired at the noncontrast phase (NCP), arterial phase (AP), and venous phase (VP). The least absolute shrinkage and selection operator (LASSO) method was used to select the most useful predictive features extracted from the CT images. The predictive models that discriminate PSP from SMPN based on single-phase CT images (NCP, AP, and VP) or three-phase CT images (Combined model) were developed and validated through fivefold cross-validation using a logistic regression classifier. Model performance was evaluated using receiver operating characteristic (ROC) analysis. The predictive performance was also compared between the Combined model and human readers. RESULTS: Four, five, and five features were selected from NCP, AP, and VP CT images for the development of radiomic models, respectively. The NCP, AP, and VP models exhibited areas under the curve (AUCs) of 0.748 (95% confidence interval [CI], 0.620-0.852), 0.749 (95% CI, 0.620-0.852), and 0.790 (95% CI, 0.665-0.884) in the validation dataset, respectively. The Combined model based on three-phase CT images outperformed the NCP, AP, and VP models (all p < 0.05), yielding an AUC of 0.882 (95% CI, 0.773-0.951) in the validation dataset. The Combined model displayed noninferior performance compared to two senior radiologists; however, it outperformed two junior radiologists (p = 0.004 and 0.001, respectively). CONCLUSION: The Combined model based on radiomic features extracted from three-phase CT images achieved radiologist-level performance and could be used as promising noninvasive tool to differentiate PSP from SMPN.

Repair of Defects in the Scalp and Face With Expanded Superficial Temporal Artery Flaps: A Single-Center Retrospective Study.

BACKGROUND AND OBJECTIVE: Defects resulted from the removal of large scars, benign tumors, severe pigmentation abnormalities, and vascular malformations, etc., in the scalp and face need to be repaired to restore the appearance. Here, the authors introduced the application of various expanded superficial temporal artery (STA) flaps in the repair of above defects. METHODS: From Jan. 2015 to Dec. 2018, 19 patients with craniofacial secondary defects received the repair with expanded STA flaps in our clinic. The defects were resulted from the removal of scalp scar (n = 6), neurofibroma (n = 4), sebaceous nevus (n = 3), arteriovenous malformation (n = 2), facial scar (n = 2), and port-wine stain (n = 2). The expanded STA flaps included 14 cases of flaps pedicled by parietal branch of STA, 2 cases of flaps pedicled by parietal branch of STA combined with laser hair removal, 1 case of flaps pedicled by frontal branch of STA, and 2 cases of prefabricated expanded skin flap with the superficial temporal fascia in the neck. RESULTS: The two-stage operation and water-filling expansion were accomplished in all patients. All flaps survived well, except one flap with venous congestion, which resolved after blood-letting and application of drugs promoting venous draining. In the three to six months follow-up, the flaps' color, texture, and thickness were satisfying. CONCLUSIONS: Individual application of different types of expanded STA flaps could achieve ideal results in repairing craniofacial secondary defects.

Zinc Recovery from Wulagen Sulfide Flotation Plant Tail by Applying Ether Amine Organic Collectors.

Separating oxidized zinc minerals from flotation tailings is always a challenge. In this study, a flotation tailing from Wulagen zinc mine in China (Zn grade < 1%) was processed using froth flotation with combinations of amines (OPA 10, OPA 1214, OPA 13, DDA) and Na2S to study the effects of these amines on the zinc recovery as well as their interactions with other reagents, aiming to screen out a proper reagent scheme to improve zinc separation from extremely low-grade zinc flotation tailings. The results show that different amines led to different flotation performance, and the collectors were ranked as OPA 1214, OPA 13, OPA 10 and DDA in a decreasing order based on flotation collectivity and selectivity. An increase in the concentration of each collector increased the zinc recovery but reduced the concentrate zinc grade. Interactions were also observed between different amines and Na2S and Na2SiO3, and OPA 1214 outdid the others in saving the usage of both the Na2S and Na2SiO3. The measured adsorption of collector onto smithsonite was found to correlate well with flotation test results. It was concluded that hydrocarbon chains can be held accountable for the difference in the flotation performance with different amines. The longer the hydrocarbon chain, the stronger the hydrophobic association ability of amine, which is conducive to the selective amine adsorption onto sulfurized smithsonite particles and hence the smithsonite flotation.