Phase transition kinetics of superionic H2O ice phases revealed by Megahertz X-ray free-electron laser-heating experiments.

H2O transforms to two forms of superionic (SI) ice at high pressures and temperatures, which contain highly mobile protons within a solid oxygen sublattice. Yet the stability field of both phases remains debated. Here, we present the results of an ultrafast X-ray heating study utilizing MHz pulse trains produced by the European X-ray Free Electron Laser to create high temperature states of H2O, which were probed using X-ray diffraction during dynamic cooling. We confirm an isostructural transition during heating in the 26-69 GPa range, consistent with the formation of SI-bcc. In contrast to prior work, SI-fcc was observed exclusively above ~50 GPa, despite evidence of melting at lower pressures. The absence of SI-fcc in lower pressure runs is attributed to short heating timescales and the pressure-temperature path induced by the pump-probe heating scheme in which H2O was heated above its melting temperature before the observation of quenched crystalline states, based on the earlier theoretical prediction that SI-bcc nucleates more readily from the fluid than SI-fcc. Our results may have implications for the stability of SI phases in ice-rich planets, for example during dynamic freezing, where the preferential crystallization of SI-bcc may result in distinct physical properties across mantle ice layers.

[Genomic profiles and immune microenvironment of olfactory neuroblastoma].

Objective: To investigate the genomic profiles and immune microenvironment of olfactory neuroblastoma (ONB). Methods: Nineteen ONB cases diagnosed in the Beijing Tongren Hospital from May 2018 to October 2022 were divided into low-grade and high-grade groups according to the Hyams grading system, including 7 low-grade and 12 high-grade ONB. Whole exome sequencing and multiplex immunofluorescence analyses were performed on tissue samples of these ONB. Results: A total of 929 nonsynonymous alterations were identified in 18 of the 19 ONB (18/19) cases. The most commonly altered cancer-related genes were CTNNB1 (3/19) and ZNRF3 (3/19). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45/Mb, ranging from 0 to 3.25. The median tumor neoantigen load (TNB) was 9.39 neoantigens/Mb, ranging from 0 to 38.30. The median allelic mutation tumor heterogeneity (MATH) score was 16.95, ranging from 3.05 to 117.47. Only one of the 19 cases expressed PD-L1 (composite positive score, CPS>1) in the tumor cells. The median percentage of CD8+ tumor-infiltrating lymphocyte (TIL) in the tumor region was 1.08%. No significant differences were observed between the low-and high-grade groups for mutant genes, mutant pathways, TMB, TNB, MATH, PD-L1 expression levels, or CD8+ TILs percentage(P>0.05). However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.52% of CD68+ macrophages. Conclusions: CTNNB1 and ZNRF3 are the most commonly altered cancer-related genes. The low expression of PD-L1 and the low percentage of CD8+ TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.

[Dihydroartemisinin enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis by promoting ROS production].

OBJECTIVE: To investigate the effect of dihydroartemisinin (DHA) for enhancing the inhibitory effect of cisplatin (DDP) on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism. METHODS: CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA (0, 5, 10, 20, 40, 80, and 160 µmol/L) and DDP (0, 4, 8, 16, 32, 64, 128 µmol/L) for 24 or 48 h, and the combination index of DHA and DDP was calculated using Compusyn software. HNE1/DDP cells treated with DHA, DDP, or their combination for 24 h were examined for cell viability, proliferation and colony formation ability using CCK-8, EdU and colony-forming assays. Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species (ROS). The expression levels of apoptosis-related proteins cleaved PARP, cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting. The effects of N-acetyl-cysteine (a ROS inhibitor) on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed. RESULTS: Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells. The combination index of DHA (5 µmol/L) combined with DDP (8, 16, 32, 64, 128 µmol/L) were all below 1. Compared with DHA or DDP alone, their combined treatment more potently decreased the cell viability, colony-forming ability and the number of EdU-positive cells, and significantly increased the apoptotic rate, intracellular ROS level, and the expression levels of cleaved PARP, cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells. N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells (P<0.01). CONCLUSION: DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

[Research progress of radiomics in hepatocellular carcinoma].

Primary liver cancer is a common malignant digestive system tumor, with hepatocellular carcinoma being the most common pathological type. Radiomics significantly boosts the efficiency of predictions by accurately capturing the intrinsically heterogeneous features of tumors that are difficult to discern with the human eye in imaging images. This article outlines the background and concepts of radiomics, introduces its latest research progress in various aspects, such as diagnosis and differential diagnosis, prediction of pathological molecular subtypes, efficacy evaluation, and survival prediction, and further discusses its limitations and prospects in HCC.

[Correlation of body composition indicators with exercise capacity and nutritional status in male patients with chronic obstructive pulmonary disease].

Objective: To investigate the correlation of body composition indices with exercise capacity and nutritional status in male chronic obstructive pulmonary disease (COPD) patients. Methods: The clinical data of 90 male COPD patients admitted to the Department of Respiratory and Critical Care Medicine of China-Japan Friendship Hospital from January 2021 to September 2022 were retrospectively collected, and the patients were subjected to a pulmonary function test, body composition measurement, 6-minute walking test distance (6MWD) test, and dominant handgrip strength measurement (HGS). The patients were categorized into COPD Global Initiative for COPD (GOLD) grade 1, 2, 3 and 4 groups according to the severity of lung function. Based on the fat-free mass index (FFMI), patients were categorized into a low FFMI group (FFMI<17 kg/m2) and a normal FFMI group (FFMI≥17 kg/m2). Based on phase angle (PhA), patients were categorized into the low PhA group (PhA<5°) and the normal PhA group (PhA≥5°). Based on 6MWD, patients were divided into impaired endurance group (6MWD<350 m) and normal endurance group (6MWD≥350 m). Differences in body composition indexes, exercise capacity, and nutritional status of patients in different subgroups were compared. A trend test was used to analyze the trend of GOLD grading and body composition indexes. Correlation analysis was used to analyze the correlation of FFMI, PhA, skeletal muscle mass index (SMI), basal metabolic rate (BMR), and visceral fat index (VFI) with 6MWD, HGS, post-diastolic exertional expiratory volume in the first second as a percentage of exertional lung capacity (FEV1%pred), and body mass index (BMI). Results: The age of 90 male COPD patients was 66 (59, 71) years. FFMI, PhA, SMI, BMR, VFI, HGS, and 6MWD tended to decrease with increasing GOLD levels (all P<0.05). In the low FFMI group (31 cases), PhA [5.0° (4.7°, 5.1°) vs 5.8° (5.6°, 6.3°)], SMI [6.3 (5.3, 6.9)vs 8.3 (7.7, 9.1) kg/m2], and BMR [(1 294.5±387.2) vs (1 538.7±207.5) kcal(1 kcal=4.184 kJ)], VFI [(10.0±4.2) grades vs (14.2±3.3) grades], 6MWD [(430.5±90.8) vs (537.2±85.5) m], FEV1%pred [(37.8±7.9)% vs (73.7±21.5)%], BMI [(20.2±3.8) vs (25.5±2.9) kg/m2] were lower than those in the normal FFMI group (59 cases, all P<0.05). In the low PhA group (23 cases), FFMI [(16.7±2.2) vs (19.5±1.5) kg/m2], SMI [6.6 (5.9, 7.0) vs 7.3 (7.7, 9.0) kg/m2], BMR [(1 251.8±246.2) vs (1 547.5±206.6) kcal], 6MWD [(451.0±47.1) vs (538.3±87.5) m], HGS [(29.6±4.0) vs (36.4±7.2) kg], FEV1%pred [(51.2±15.3)% vs (72.9±22.8)%], BMI [(20.9±3.7) vs (25.5±2.8) kg/m2] were lower than those of the normal PhA group (67 cases, all P<0.05). In the impaired endurance group (21 cases) PhA [5.2° (5.1°, 5.3°) vs 5.8° (5.6°, 6.3°)], FEV1%pred [(34.2±15.4)% vs (72.7±22.2)%] were lower than those in the normal endurance group (69 cases, all P<0.05). Correlation analysis showed that FFMI was positively correlated with HGS, FEV1%pred, and BMI (r values of 0.327, 0.235, and 0.782, all P<0.05); PhA was positively correlated with 6MWD, FEV1%pred, and BMI (r values of 0.341, 0.258, and 0.251, all P<0.05); SMI was positively correlated with HGS and BMI (r values of 0.411 and 0.710, all P<0.05); BMR was positively correlated with 6MWD, HGS, FEV1%pred, and BMI (r values of 0.338, 0.508, 0.285, and 0.676, all P<0.05); VFI was positively correlated with BMI (r value of 0.791, P<0.001). Conclusions: FFMI is positively correlated with HGS, FEV1%pred, and BMI; PhA is positively correlated with 6MWD, FEV1%pred, and BMI; SMI is positively correlated with HGS and BMI; BMR is positively correlated with 6MWD, HGS, FEV1%pred, and BMI; VFI is positively correlated with BMI. Body composition indexes may reflect the exercise capacity and nutritional status of male COPD patients.

A phase 2 feasibility study of nab-paclitaxel and carboplatin in epithelial carcinoma of the uterus.

BACKGROUND: We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks. METHODS: Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. RESULTS: From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months. CONCLUSIONS: The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.

Efficacy of photodynamic therapy for oral multifocal papilloma: a case report.

Oral papilloma, a frequently encountered benign lesion, can be managed effectively with various treatments. A unique case of oral mucosal papilloma extending from the buccal fat pad region to the corner of the mouth is presented here. Although papilloma larger than 10 mm2 are associated with a high risk of becoming cancerous and should be treated promptly, the papilloma in this case would have been difficult to resect due to involvement of the parotid duct opening and the corner of the mouth. Topical external application of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) was employed successfully in this case, with no recurrence at 20 months of follow-up. Therefore, ALA-PDT may represent a promising therapeutic option for challenging cases of multifocal papilloma of the oral mucosal.

[Transverse sinus blood flow characteristics of pulsatile tinnitus with dehiscent sigmoid plate based on 4D flow MRI].

Objective: To investigate the hemodynamic characteristics of transverse sinus with sigmoid sinus wall dehiscence (SSWD) of pulsatile tinnitus (PT) based on 4D flow MRI. Methods: Retrospective analysis was performed on all patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2021 for dehiscent sigmoid plate pulsatile tinnitus. A total of 26 patients (sides) who met the criteria and underwent 4D flow MRI were included. A total of 26 subjects (46 sides), matched 1∶1 according to gender and age, were included in the normal healthy control group. Nonparametric rank sum test, Student's t test, and ANOVA were performed by SPSS 19.0 software. Binary Logistic regression was applied to the data with statistical significance. Results: There were more patients with dominant drainage on the affected side in PT group than in control group (73.1% vs. 42.3%). The incidence of transverse with a focal intraluminal filling defect and tapered stenosis was higher than that in control group (21.7% vs. 69.2%; 17.4% vs. 42.3%). Average through-plane velocity and maximum through-plane velocity in PT group were higher than those in control group [(33.75±13.88) cm/s vs. (15.84±7.21) cm/s; (93.19±33.55) cm/s vs. (40.40±14.40) cm/s]. The middle part and proximal end of Flowavg (ml/s) in PT group were larger than those in control group [4.69 (2.87; 5.62) ml/s vs. 2.76 (1.67; 4.99) ml/s; 3.41 (2.16; 5.47) ml/s vs. 2.67 (1.68; 4.41) ml/s]. In control group, the velocity of transverse sinus changed relatively gently, while in PT group, the velocity of proximal sinus increased significantly. Binary Logistic regression showed that SSWD PT was independently correlated with proximal maximum flow velocity [OR=1.086(1.029-1.146),P=0.003]. Conclusion: 4D flow MRI showed that the dominant drainage and higher velocity at the proximal end of the transverse sinus might be an important hemodynamic characteristics of dehiscent sigmoid plate pulsatile tinnitus.

[Progress in the study of the correlation between dyslipidemia and demyelinating diseases of the nervous system].

Demyelinating disorders of the nervous system constitute a broad spectrum of neurological conditions characterized by the depletion of myelin sheaths accompanied by inflammatory cell infiltration, manifesting in either the central or peripheral nervous system. The former primarily encompasses conditions such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), while the latter is exemplified predominantly by Guillain-Barre syndrome (GBS). Recent investigations have revealed that dyslipidemia may be related to the occurrence and development of neurological demyelination, but there are fewer analyses and summaries of related advances in China. Consequently, this review aims to comprehensively outline advancements in research concerning the correlation between dyslipidemia and neurological demyelinating disordersand discusses in depth the interrelationship between dyslipidemia and neurological demyelinating diseases, so as to provide reference for the prevention and treatment of neurological demyelinating diseases.

Use of birth weight as a predictor of genetic merit of subsequent growth traits in Duroc and Landrace pigs.

Analysis of correlation between the early testable phenotypes of piglets and the final performance of pigs can serve the early selection for breeding. The objectives of this study were to estimate the genetic parameters for birth weight (BtW), age (AGE) and backfat thickness (BF) up to 115 kg BW and to analyse the relationships among these three traits, and to estimate the accuracy of using BtW to predict estimated breeding values (EBVs) of AGE and BF in Landrace and Duroc pigs. Data on 26 614 Landrace and 19 984 Duroc pigs, born between 2001 and 2018, were collected from the core breeding group of a farm. All pigs were recorded for phenotypes including BtW, AGE and BF. The factors affecting these three traits were analysed using R v4.2.0 Software. The population genetic parameters and breeding values of three traits were estimated by using a multitrait animal model based on AI plate of DMU software. Heritabilities for BtW, AGE and BF were moderate to high for Landrace (0.437, 0.282and 0.137, respectively) and Duroc breeds (0.369, 0.279 and 0.148). BtW was genetically correlated with AGE and BF in Landrace (-0.213, 0.037) and Duroc (-0.214, 0.025). AGE was negatively genetically correlated with BF in both Landrace (-0.036) and Duroc (-0.057) pigs. The heritability of BtW, AGE and BF of Landrace pigs and Duroc pigs were 0.148, 0.182 and 0.075 and 0.168, 0.159 and 0.120, respectively, by taking into account of the litter effect. BtW was genetically correlated with AGE and BF in Landrace (-0.094, 0.002) and Duroc (-0.199, -0.052). AGE was negatively genetically correlated with BF in both Landrace (-0.034) and Duroc (-0.153) pigs. The variances between total individual BtW and AGE and BF were then used to predict the EBV of AGE and BF for individuals with AGE or BF phenotypes missing under 10-fold cross-validation. Prediction accuracy was calculated as the Kendall tau-b correlation coefficient between EBVs and EBVs via 10-fold cross-validation. Prediction accuracy for AGE and BF was 0.655 and 0.611 in Landrace, 0.665 and 0.617 in Duroc. After incorporation of the litter effect, the prediction accuracy for AGE and BF increased to 0.690 and 0.665 in Landrace and to 0.705 and 0.649 in Duroc. So, the EBV of AGE and BF phenotypes missing individuals could be predicted by using the available phenotypic data and the easily measured BtW, and litter effect could boost the accuracy of prediction.

Novel DGAT1 Mutations Identified in Congenital Diarrheal Disorder 7: A Case Report with Therapeutic Experience.

Congenital diarrheal disorders (CDD) are a group of rare inherited intestinal disorders, among which CDD7 was recently identified to be associated with only 24 mutations in gene coding for diacylglycerol-acyltransferase 1 (DGAT1). We report on a female patient who presented with diarrhea, vomiting, hypoalbuminemia, and failure to thrive after birth. Two novel variants of c.1215_1216delAG and c.838C>T were found in the DGAT1 gene by whole exome sequencing, which was confirmed to be compound heterozygous by Sanger sequencing. Her symptoms and nutritional status improved significantly after 1 year of a fat-restricted enteral diet. Weight for age and weight for length increased from -5.0 SDS and -4.0 SDS at 3 months to +0.08 SDS and +1.75 SDS at 15 months, respectively. This report expanded the mutation spectrum of DGAT1-related CDD7 and enriched our knowledge of the clinical features. Moreover, early fat-restricted enteral diet intervention was suggested for the treatment of such patients.