The third case of Marbach-Rustad progeroid syndrome caused by a de novo LEMD2 variant.

Marbach-Rustad progeroid syndrome is an extremely rare disease caused by a heterozygous variant in the LEMD2 gene. To date, only two patients and one LEMD2 pathogenic variant have been reported in Marbach-Rustad progeroid syndrome. Here we describe the third case of Marbach-Rustad progeroid syndrome worldwide, which is also the first case in China. The proband was affected with premature birth, failed to thrive, facial abnormalities, feeding difficulties, skull defects and delayed motor milestones, but had a normal intelligence and speech. Whole exome sequencing (WES) initially did not find a phenotype-causing variant when the proband was 1 year of age. The reanalysis of WES data 4 years later revealed the proband harbored a de novo heterozygous c.1436C>T(p.Ser479Phe) variant in the LEMD2 gene, which is known responsible for Marbach-Rustad progeroid syndrome. Sanger sequencing confirmed the presence of this variant in the proband and absence in his parents and two elder sisters. Our study provides accurate clinical diagnosis for the proband and adds a new patient with Marbach-Rustad progeroid syndrome. Our study suggests the LEMD2 c.1436C>T(p.Ser479Phe) variant as a hotspot. Our work also indicates reanalysis of WES data of negative cases might identify pathogenic variant and improve diagnostic efficiency.

Clinical-Radiologic Morphology-Radiomics Model on Gadobenate Dimeglumine-Enhanced MRI for Identification of Highly Aggressive Hepatocellular Carcinoma: Temporal Validation and Multiscanner Validation.

BACKGROUND: Highly aggressive hepatocellular carcinoma (HCC) is characterized by high tumor recurrence and poor outcomes, but its definition and imaging characteristics have not been clearly described. PURPOSE: To develop and validate a fusion model on gadobenate dimeglumine-enhanced MRI for identifying highly aggressive HCC. STUDY TYPE: Retrospective. POPULATION: 341 patients (M/F = 294/47) with surgically resected HCC, divided into a training cohort (n = 177), temporal validation cohort (n = 77), and multiscanner validation cohort (n = 87). FIELD STRENGTH/SEQUENCE: 3T, dynamic contrast-enhanced MRI with T1-weighted volumetric interpolated breath-hold examination gradient-echo sequences, especially arterial phase (AP) and hepatobiliary phase (HBP, 80-100 min). ASSESSMENT: Clinical factors and diagnosis assessment based on radiologic morphology characteristics associated with highly aggressive HCCs were evaluated. The radiomics signatures were extracted from AP and HBP. Multivariable logistic regression was performed to construct clinical-radiologic morphology (CR) model and clinical-radiologic morphology-radiomics (CRR) model. A nomogram based on the optimal model was established. Early recurrence-free survival (RFS) was evaluated in actual groups and risk groups calculated by the nomogram. STATISTICAL TESTS: The performance was evaluated by receiver operating characteristic curve (ROC) analysis, calibration curves analysis, and decision curves. Early RFS was evaluated by using Kaplan-Meier analysis. A P value <0.05 was considered statistically significant. RESULTS: The CRR model incorporating corona enhancement, cloud-like hyperintensity on HBP, and radiomics signatures showed the highest diagnostic performance. The area under the curves (AUCs) of CRR were significantly higher than those of the CR model (AUC = 0.883 vs. 0.815, respectively, for the training cohort), 0.874 vs. 0.769 for temporal validation, and 0.892 vs. 0.792 for multiscanner validation. In both actual and risk groups, highly and low aggressive HCCs showed statistically significant differences in early recurrence. DATA CONCLUSION: The clinical-radiologic morphology-radiomics model on gadobenate dimeglumine-enhanced MRI has potential to identify highly aggressive HCCs and non-invasively obtain prognostic information. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Clinical and multiparametric MRI features for differentiating uterine carcinosarcoma from endometrioid adenocarcinoma.

INTRODUCTION: The purpose of our study was to differentiate uterine carcinosarcoma (UCS) from endometrioid adenocarcinoma (EAC) by the multiparametric magnetic resonance imaging (MRI) features. METHODS: We retrospectively evaluated clinical and MRI findings in 17 patients with UCS and 34 patients with EAC proven by histologically. The following clinical and pathological features were evaluated: post- or pre-menopausal, clinical presentation, invasion depth, FIGO stage, lymphaticmetastasis. The following MRI features were evaluated: tumor dimension, cystic degeneration or necrosis, hemorrhage, signal intensity (SI) on T2-weighted images (T2WI), relative SI of lesion to myometrium on T2WI, T1WI, DWI, ADCmax, ADCmin, ADCmean (RSI-T2, RSI-T1, RSI-DWI, RSI-ADCmax, RSI-ADCmin, RSI-ADCmean), ADCmax, ADCmin, ADCmean, the maximum, minimum and mean relative enhancement (RE) of lesion to myometrium on the arterial and venous phases (REAmax, REAmin, REAmean, REVmax, REVmin, REVmean). Receiver operating characteristic (ROC) analysis and the area under the curve (AUC) were used to evaluate prediction ability. RESULTS: The mean age of UCS was higher than EAC. UCS occurred more often in the postmenopausal patients. UCS and EAC did not significantly differ in depth of myometrial invasion, FIGO stage and lymphatic metastasis. The anterior-posterior and transverse dimensions were significantly larger in UCS than EAC. Cystic degeneration or necrosis and hemorrhage were more likely occurred in UCS. The SI of tumor on T2WI was more heterogeneous in UCS. The RSI-T2, ADCmax, ADCmean, RSI-ADCmax and RSI-ADCmean of UCS were significantly higher than EAC. The REAmax, REAmin, REAmean, REVmax, REVmin and REVmean of UCS were all higher than EAC. The AUCs were 0.72, 0.71, 0.86, 0.96, 0.89, 0.84, 0.73, 0.97, 0.88, 0.94, 0.91, 0.69 and 0.80 for the anterior-posterior dimension, transverse dimension, RSI-T2, ADCmax, ADCmean, RSI-ADCmax, RSI-ADCmean, REAmax, REAmin, REAmean, REVmax, REVmin and REVmean, respectively. The AUC was 0.997 of the combined of ADCmax, REAmax and REVmax. Our study showed that ADCmax threshold value of 789.05 (10-3mm2/s) can differentiate UCS from EAC with 100% sensitivity, 76.5% specificity, and 0.76 AUC, REAmax threshold value of 0.45 can differentiate UCS from EAC with 88.2% sensitivity, 100% specificity, and 0.88 AUC. CONCLUSION: Multiparametric MRI features may be utilized as a biomarker to distinguish UCS from EAC.

Comparative transcriptome analyses of three Gentiana species provides signals for the molecular footprints of selection effects and the phylogenetic relationships.

Species in Gentiana section Cruciata are important alpine plants with a center of diversity and speciation in Qinghai-Tibet Plateau (QTP), and some of these species are sympatrically distributed in northeastern QTP. Studies on genome features and natural selection signatures of sympatric species in section Crucata have been impeded by a lack of genomic resources. Here, we showed transcript characterizations and molecular footprints of selection effects on G. straminea, G. dahurica and G. officinalis based on the comparative transcriptome. A total of 62.97 Gb clean reads were obtained with unigene numbers per species ranging from 141,819 to 236,408 after assembly. We found that these three species had similar distribution of functional categories in different databases, and key enzyme-encoding genes involved in the iridoids biosynthesis were also obtained. The selective pressure analyses indicated that most paired orthologs between these three species were subject to negative selection, and only a low proportion of the orthologs that underwent positive selection were detected. We found that some positive selected genes were involved in "catalytic activity", "metabolic process", "response to stimulus" and "response to stress". Besides, large numbers of SSR primer pairs with transferabilities were successfully designed based on the available transcriptome datasets of three Gentiana species. The phylogenetic relationships reconstructed based on 352 single-copy nuclear genes provided a rough phylogenetic framework for this genus and confirmed the monophyly of section Cruciata. Our study not only provides insights for the natural selection effects on sympatric Gentiana species, but also enhances future genetic breeding or evolutionary studies on Qinjiao species.

Clinic-radiological features and radiomics signatures based on Gd-BOPTA-enhanced MRI for predicting advanced liver fibrosis.

OBJECTIVES: To develop and validate a combined model based on Gd-BOPTA-enhanced MRI to identify advanced liver fibrosis. METHODS: A total of 102 patients with chronic HBV infection were divided into a training cohort (n = 80) and a time-independent testing cohort 1 (n = 22). In the training cohort, radiomics signatures were extracted from the hepatobiliary phase. Model 1 was constructed with clinic-radiological factors using multivariable logistic regression to predict advanced liver fibrosis, and model 2 incorporated radiomics signatures based on model 1. The diagnostic performances were compared with serum fibrosis tests and FibroScan tests using area under curve (AUC) in testing cohort 1. Another 45 patients with other causes were collected in testing cohort 2 for further validation. RESULTS: Model 1 showed age (OR = 1.079) and periportal space widening (OR = 7.838) were the independent factors for predicting advanced fibrosis. After integrating radiomics signatures, model 2 enabled more accurately than model 1 in training cohort (0.940 vs. 0.802, p = 0.003). In testing cohort 1, model 2 demonstrated a superior AUC compared with model 1 (0.900 vs. 0.813，p = 0.131), FibroScan test (0.900 vs. 0.733, p = 0.193), and serum fibrosis tests (APRI and Fib-4 was 0.667 and 0.791). In testing cohort 2, model 2 incorporating radiomics signatures showed satisfactory performance (0.874 vs. 0.757，p = 0.010) compared with model 1. CONCLUSIONS: Radiomics signatures derived from Gd-BOPTA-enhanced HBP images may offer complementary information to the clinic-radiological model for predicting advanced liver fibrosis. KEY POINTS: • Linear or reticular hyperintensity on T2WI, periportal space widening, and diffuse periportal enhancement on HBP can be useful for predicting advanced liver fibrosis. • Clinic-radiological features such as patient age and periportal space widening are the two independent factors predicting advanced fibrosis. • Radiomics signatures derived from Gd-BOPTA-enhanced HBP images offer complementary information to the clinic-radiological model for predicting advanced liver fibrosis.

T1 and ADC histogram parameters may be an in vivo biomarker for predicting the grade, subtype, and proliferative activity of meningioma.

OBJECTIVE: To investigate the value of histogram analysis of T1 mapping and diffusion-weighted imaging (DWI) in predicting the grade, subtype, and proliferative activity of meningioma. METHODS: This prospective study comprised 69 meningioma patients who underwent preoperative MRI including T1 mapping and DWI. The histogram metrics, including mean, median, maximum, minimum, 10th percentiles (C10), 90th percentiles (C90), kurtosis, skewness, and variance, of T1 and apparent diffusion coefficient (ADC) values were extracted from the whole tumour and peritumoural oedema using FeAture Explorer. The Mann-Whitney U test was used for comparison between low- and high-grade tumours. Receiver operating characteristic (ROC) curve and logistic regression analyses were performed to identify the differential diagnostic performance. The Kruskal-Wallis test was used to further classify meningioma subtypes. Spearman's rank correlation coefficients were calculated to analyse the correlations between histogram parameters and Ki-67 expression. RESULTS: High-grade meningiomas showed significantly higher mean, maximum, C90, and variance of T1 (p = 0.001-0.009), lower minimum, and C10 of ADC (p = 0.013-0.028), compared to low-grade meningiomas. For all histogram parameters, the highest individual distinctive power was T1 C90 with an AUC of 0.805. The best diagnostic accuracy was obtained by combining the T1 C90 and ADC C10 with an AUC of 0.864. The histogram parameters differentiated 4/6 pairs of subtype pairs. Significant correlations were identified between Ki-67 and histogram parameters of T1 (C90, mean) and ADC (C10, kurtosis, variance). CONCLUSION: T1 and ADC histogram parameters may represent an in vivo biomarker for predicting the grade, subtype, and proliferative activity of meningioma. KEY POINTS: • The histogram parameter based on T1 mapping and DWI is useful to preoperatively evaluate the grade, subtype, and proliferative activity of meningioma. • The combination of T1 C90 and ADC C10 showed the best performance for differentiating low- and high-grade meningiomas.

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.

Objective: To determine prognostic role of endothelial progenitor cells (EPCs) in intensive care patients with acute myocardial infarction (AMI). Materials and Methods: From December 2018 to July 2021, a total of 91 eligible patients with AMI were consecutively examined in a single intensive care unit (ICU) in China. Patients with a history of acute coronary artery disease were excluded from the study. Samples were collected within 24 hr of onset of symptoms. EPCs, defined as coexpression of CD34+/CD133+ cells or CD133+/CD34+/KDR+, were studied using flow cytometry and categorized by quartiles. Based on the 28-days mortality outcome, the patients were further divided into two groups: death and survival. The study incorporated various variables, including cardiovascular risk factors such as body mass index, hypertension, diabetes, hypercholesterolemia, atherosclerotic burden, and medication history, as well as clinical characteristics such as APACHEⅡscore, central venous-arterial carbon dioxide difference (GAP), homocysteine, creatinine, C-reactive protein, HbAlc, and cardiac index. Cox regression analysis was employed to conduct a multivariate analysis. Results: A total of 91 patients with AMI who were admitted to the ICU were deemed eligible for inclusion in the study. Among these patients, 23 (25.3%) died from various causes during the follow-up period. The counts of EPCs were found to be significantly higher in the survival group compared to the death group (P < 0.05). In the univariate analysis, it was observed that the 28-days mortality rate was associated with the several factors, including the APACHEⅡscore (P=0.00), vasoactive inotropic score (P=0.03), GAP (P=0.00), HCY (P=0.00), creatinine (P=0.00), C-reactive protein (P=0.00), HbAlc (P=0.00), CI (P=0.01), quartiles of CD34+/CD133+ cells (P=0.00), and quartiles of CD34+/CD133+/KDR+ cells (P=0.00). CD34+/CD133+/KDR+ cells retained statistical significance in Cox regression models even after controlling for clinical variables (HR: 6.258 × 10-10 and P=0.001). Nevertheless, no significant correlation was observed between CD34+/CD133+ cells and all-cause mortality. Conclusions: The decreased EPCs levels, especially for CD34+/CD133+/KDR+ cells subsets, were an independent risk factor for 28-days mortality in AMI patients.

An Isolable Radical Anion Featuring a 2-Center-3-Electron π-Bond without a Clearly Defined σ-Bond.

Featuring an extra electron in the π* antibonding orbital, species with a 2-center-3-electron (2c3e) π bond without an underlying σ bond are scarcely known. Herein, we report the synthesis, isolation and characterization of a radical anion salt [K(18-C-6)]+ {[(HCNDipp)2 Si]2 P2 }⋅- (i.e. [K(18-C-6)]+ 3⋅- ) (18-C-6=18-crown-6, Dipp=2,6-diisopropylphenyl), in which 3⋅- features a perfectly planar Si2 P2 four-membered ring. This species represents the first example of a Si- and P-containing analog of a bicyclo[1.1.0]butane radical anion. The unusual bonding motif of 3⋅- was thoroughly investigated via X-ray diffraction crystallography, electron paramagnetic resonance spectroscopy (EPR), and calculations by density functional theory (DFT), which collectively unveiled the existence of a 2c3e π bond between the bridgehead P atoms and no clearly defined supporting P-P σ bond.

KCC2 receptor upregulation potentiates antinociceptive effect of GABAAR agonist on remifentanil-induced hyperalgesia.

GABAergic system disinhibition played an important role in the pathogenesis of remifentanil-induced hyperalgesia (RIH). K+-Cl--cotransporter-2 (KCC2) has the potential to enhance the strength of GABAergic signaling function. However, few reports have focused on the additive analgesic effect of KCC2 enhancer and GABAA receptor agonist on the spinal dorsal horn. Therefore, we evaluated the role of GABA type A receptor (GABAAR) agonist (muscimol), KCC2 enhancer (CLP257) in remifentanil-induced hyperalgesia, as well as GABA and KCC2 receptors responses in the dorsal spinal horn. Remifentanil started to reduce paw withdrawal mechanical thresholds at postoperative 4 h and lasted to 72 h. The RIH associated decreases in spinal GABA release was transient. The amount of spinal GABA transmitter by microdialysis was observed to be decreased at the beginning and reached bottom at 150 min, then returned to the baseline level at 330 min. The synthesis and transportation of GABA transmitter were inhibited, characterized as spinal GAD67 and GAT1 downregulation after the establishment of RIH model. The effect of RIH on GABA receptor downregulation was linked to the reduced expression of spinal KCC2 receptor. This decrease in KCC2 expression has coincided with an early loss of GABA inhibition. KCC2 enhancer, which is reported to lead to a reduction in intracellular Cl-, can enhance GABA-mediated inhibitory function. Both muscimol and CLP257 could dose-dependently inhibit mechanical hypersensitivity caused by remifentanil-induced downregulation of GABAAα2R and KCC2, respectively. Compared with muscimol acting alone, the joint action of CLP257 and muscimol showed a higher pain threshold and less c-fos expression via upregulation of KCC2 and GABAAα2R. Taken together, these findings suggested that the RIH was initiated by decreased GABA release. Downregulation of GABAAα2R and KCC2 receptor contributed to spinally mediated hyperalgesia in RIH. KCC2 enhancer was proved to potentiate antinociceptive effect of GABAAR agonist in RIH.

Human iPSC-derived neural stem cells with ALDH5A1 mutation as a model of succinic semialdehyde dehydrogenase deficiency.

BACKGROUND: Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is an autosomal recessive gamma-aminobutyric acid (GABA) metabolism disorder that can arise due to ALDH5A1 mutations, resulting in severe, progressive, untreatable neurodegeneration. SSADH-D is primarily studied using simplified models, such as HEK293 cells overexpressing genes of interest, but such overexpression can result in protein aggregation or pathway saturation that may not be representative of actual underlying disease phenotypes. METHODS: We used a CRISPR/Cas9 approach to generate human iPSC cell lines bearing ALDH5A1 mutations. Through screening, two different mutant cell lines, NM_001080.3: c.727_735del (p.L243_S245del) and NM_001080.3: c.730_738del (p.A244_Q246del), were obtained. We induced iPSCs to neural stem cells and analyzed the characteristics of ALDH5A1 mutations in stem cells. RESULTS: The human iPSC and NSC cell lines presented typical stem cell-like morphology. We found changes in ALDH5A1 expression and GABA accumulation in the different cell lines. In addition, by analyzing the cDNA between the wild-type and the mutant cell lines, we found that the mutant cell lines had a splicing variant. CONCLUSIONS: iPSCs represent a promising in vitro model for SSADH-D that can be used to study early central nervous system developmental alterations and pathogenic mechanisms.

The first Chinese case of Siddiqi syndrome caused by a homozygous FITM2 variant.

A. The family pedigree. B. Whole exome sequencing of the proband-parent trio revealed c.611_612dupTG(p.M205*) variant of FITM2 gene as suspicious variant. C. Sanger sequencing confirmed that c.611_612dupTG(p.M205*) variant of FITM2 gene was homozygous in the proband, while the unaffected parents were heterozygous.

Computer-aided classification of MRI for pathological complete response to neoadjuvant chemotherapy in breast cancer.

Background: To determine suitable optimal classifiers and examine the general applicability of computer-aided classification to compare the differences between a computer-aided system and radiologists in predicting pathological complete response (pCR) from patients with breast cancer receiving neoadjuvant chemotherapy. Methods: We analyzed a total of 455 masses and used the U-Net network and ResNet to execute MRI segmentation and pCR classification. The diagnostic performance of radiologists, the computer-aided system and a combination of radiologists and computer-aided system were compared using receiver operating characteristic curve analysis. Results: The combination of radiologists and computer-aided system had the best performance for predicting pCR with an area under the curve (AUC) value of 0.899, significantly higher than that of radiologists alone (AUC: 0.700) and computer-aided system alone (AUC: 0.835). Conclusion: An automated classification system is feasible to predict the pCR to neoadjuvant chemotherapy in patients with breast cancer and can complement MRI.

Identifying and distinguishing of essential tremor and Parkinson's disease with grouped stability analysis based on searchlight-based MVPA.

BACKGROUND: Since both essential tremor (ET) and Parkinson's disease (PD) are movement disorders and share similar clinical symptoms, it is very difficult to recognize the differences in the presentation, course, and treatment of ET and PD, which leads to misdiagnosed commonly. PURPOSE: Although neuroimaging biomarker of ET and PD has been investigated based on statistical analysis, it is unable to assist the clinical diagnosis of ET and PD and ensure the efficiency of these biomarkers. The aim of the study was to identify the neuroimaging biomarkers of ET and PD based on structural magnetic resonance imaging (MRI). Moreover, the study also distinguished ET from PD via these biomarkers to validate their classification performance. METHODS: This study has developed and implemented a three-level machine learning framework to identify and distinguish ET and PD. First of all, at the model-level assessment, the searchlight-based machine learning method has been used to identify the group differences of patients (ET/PD) with normal controls (NCs). And then, at the feature-level assessment, the stability of group differences has been tested based on structural brain atlas separately using the permutation test to identify the robust neuroimaging biomarkers. Furthermore, the identified biomarkers of ET and PD have been applied to classify ET from PD based on machine learning techniques. Finally, the identified biomarkers have been compared with the previous findings of the biology-level assessment. RESULTS: According to the biomarkers identified by machine learning, this study has found widespread alterations of gray matter (GM) for ET and large overlap between ET and PD and achieved superior classification performance (PCA + SVM, accuracy = 100%). CONCLUSIONS: This study has demonstrated the significance of a machine learning framework to identify and distinguish ET and PD. Future studies using a large data set are needed to confirm the potential clinical application of machine learning techniques to discern between PD and ET.

A novel variant in SLC16A2 associated with typical Allan-Herndon-Dudley syndrome: a case report.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked recessive neurodegenerative disorder caused by mutations in the SLC16A2 gene that encodes thyroid hormone transporter. AHDS has been rarely reported in China. CASE PRESENTATION: This study reported a novel splicing mutation in the SLC16A2 gene in an 18-month-old male patient with AHDS. The patient was born to non-consanguineous, healthy parents of Chinese origin. He passed new-born screening for hypothyroidism, but failed to reach developmental milestones. He presented with hypotonia, severe mental retardation, dysarthria and ataxia. Genetic analysis identified a novel splicing mutation, NM_006517.4: c.431-2 A > G, in the SLC16A2 gene inherited from his mother. The patient received Triac treatment, (triiodothyroacetic acid), a thyroid hormone analogue for 3 months. Triac treatment effectively reduced serum TSH concentrations and normalized serum T3 concentrations in the patient. CONCLUSIONS: This study reported the first case of AHDS treated by Triac in China. And the study expanded the mutational spectrum of the SLC16A2 gene in AHDS patients.

Ferroptosis Related Immunomodulatory Effect of a Novel Extracellular Polysaccharides from Marine Fungus Aureobasidium melanogenum.

Marine fungi represent an important and sustainable resource, from which the search for novel biological substances for application in the pharmacy or food industry offers great potential. In our research, novel polysaccharide (AUM-1) was obtained from marine Aureobasidium melanogenum SCAU-266 were obtained and the molecular weight of AUM-1 was determined to be 8000 Da with 97.30% of glucose, 1.9% of mannose, and 0.08% galactose, owing to a potential backbone of α-D-Glcp-(1→2)-α-D-Manp-(1→4)-α-D-Glcp-(1→6)-(SO3-)-4-α-D-Glcp-(1→6)-1-ß-D-Glcp-1→2)-α-D-Glcp-(1→6)-ß-D-Glcp-1→6)-α-D-Glcp-1→4)-α-D-Glcp-6→1)-[α-D-Glcp-4]26→1)-α-D-Glcp and two side chains that consisted of α-D-Glcp-1 and α-D-Glcp-(1→6)-α-D-Glcp residues. The immunomodulatory effect of AUM-1 was identified. Then, the potential molecular mechanism by which AUM-1 may be connected to ferroptosis was indicated by metabonomics, and the expression of COX2, SLC7A11, GPX4, ACSL4, FTH1, and ROS were further verified. Thus, we first speculated that AUM-1 has a potential effect on the ferroptosis-related immunomodulatory property in RAW 264.7 cells by adjusting the expression of GPX4, regulated glutathione (oxidative), directly causing lipid peroxidation owing to the higher ROS level through the glutamate metabolism and TCA cycle. Thus, the ferroptosis related immunomodulatory effect of AUM-1 was obtained.

Internal branch of superior laryngeal nerve block by dexamethasone alleviates sore throat after thyroidectomy: a randomized controlled trial.

PURPOSE: Postoperative sore throat (POST) is a common complaint following thyroidectomy. Dexamethasone was reported to alleviate POST when administered via different routes. This study aimed to compare the effects of local spray and perineural injection surrounding the internal branch of superior laryngeal nerve (iSLN) in preventing POST and alleviating postoperative impaired voice function. METHODS: A randomized, double-blinded, controlled trial was performed to test the efficacy of the iSLN block in inhibiting of POST. A total of 161 patients who underwent elective thyroidectomy were randomly allocated to two groups. Group Spray: 4 mg dexamethasone was sprayed on to the vocal cord; Group iSLN: bilateral perineural injection with 4 mg dexamethasone around the iSLN. The incidence and severity of POST, swallowing pain, and its side effects were evaluated. Postoperative acoustic analysis, including jitter and shimmer, was also performed. RESULTS: Group iSLN exhibited a significantly less incidence and intensity of POST at 6 h and 24 h (P < 0.001). The patients experienced less swallowing pain at 6 h (P < 0.001) after the surgery, compared with Group Spray. When compared with Group Spray, Group iSLN improved postoperative voice function, which was characterized by lower jitter and lower shimmer value at 6 h and 24 h (P < 0.001) after the surgery. The severity of postoperative cough is higher in Group Spray (P < 0.001). CONCLUSIONS: Among patients undergoing elective thyroidectomy, those who received perineural injection surrounding iSLN with dexamethasone had improved voice function and presented with more excellence in the inhibition of POST and cough, in comparison with the local spray. REGISTER INFORMATION: This trial was registered in the Chinese Clinical Trial Registry on 4th Jan, 2021 (ChiCTR2100042145). The trial is registered at http://www.chictr.org.cn/showproj.aspx?proj=120142 .

Comparison of case-based learning combined with Rain Classroom teaching and traditional method in complete denture course for undergraduate interns.

BACKGROUND: Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice. OBJECTIVE: This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns. METHODS: In a course called "Problems and treatment strategies of complete denture after wearing", interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns' feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher's exact test were used for statistical analysis in this study. RESULTS: The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode. CONCLUSION: Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.

Ultrasound-Guided Superior Laryngeal Nerve Block Facilitates Anesthesia Management in Bariatric Surgery.

BACKGROUND: Patients with obesity usually have a narrow pharyngeal cavity. They are prone to exposure difficulties and intubation failure during endotracheal intubation, and even face mask oxygen supply difficulties and hypoxemia in severe cases. We described the successful completion of conscious endotracheal intubation with superior laryngeal nerve internal branch block (SLNi) in a patient with pathologic obesity. CASE REPORT: A 29-year-old, nondiabetic man with severe obesity (weight 211 kg, height 186 cm, and body mass index [BMI] 60.99 kg/m2) was scheduled for a laparoscopic sleeve gastrectomy. The superior laryngeal nerve internal branch was blocked under ultrasound guidance to eliminate the cough induced by fiberscope during awake endotracheal intubation. Why Should an Emergency Physician Be Aware of This? The cough caused by fiberscope was completely suppressed and the awake endotracheal intubation was completed successfully.

Rspo1-LGR4 axis in BMSCs protects bone against radiation-induced injury through the mTOR-dependent autophagy pathway.

While mesenchymal stem cells (MSCs) have been widely used to repair radiation-induced bone damage, the molecular mechanism underlying the effects of MSCs in the maintenance of bone homeostasis under radiation stress remains largely unknown. In this study, the role and mechanisms of R-spondin 1 (Rspo1)-leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) axis on the initiation of self-defense of bone mesenchymal stem cells (BMSCs) and maintenance of bone homeostasis under radiation stress were investigated. Interestingly, radiation increased levels of Rspo1 and LGR4 in BMSCs. siRNA knockdown of Rspo1 or LGR4 aggravated radiation-induced impairment of self-renewal ability and osteogenic differentiation potential of BMSCs. However, exogenous Rspo1 significantly attenuated radiation-induced depletion of BMSCs, and promoted the lineage shift towards osteoblasts. This alteration was associated with the reversal of mammalian target of rapamycin (mTOR) activation and autophagy decrement. Pharmacological and genetic blockade of autophagy attenuated the radio-protective effects of Rspo1, rendering BMSCs more vulnerable to radiation-induced injury. Then bone radiation injury was induced in C57BL6J mice to further determine the radio-protective effects of Rspo1. In mice, administration of Rspo1 recombinant protein alleviated radiation-induced bone loss. Our results uncover that Rspo1-LGR4-mTOR-autophagy axis are key mechanisms by which BMSCs initiate self-defense against radiation and maintain bone homeostasis. Targeting Rspo1-LGR4 may provide a novel strategy for the intervention of radiation-induced bone damage.