[Cause analysis and clinical intervention of C 5 palsy after cervical surgery].

Objective: To review the research progress of C 5 palsy (C 5P) after cervical surgery, providing new clinical intervention ideas for the C 5P patients. Methods: The relevant literature domestically and abroad was extensively consulted and the latest developments in the incidence, risk factors, manifestations and diagnosis, prevention, and intervention measures of C 5P were systematically expounded. Results: C 5P is characterized by weakness in the C 5 nerve innervation area after cervical decompression surgery, manifested as limited shoulder abduction and elbow flexion, with an incidence rate more than 5%, often caused by segmental spinal cord injury or mechanical injury to the nerve roots. For patients with risk factors, careful operation and preventive measures can reduce the incidence of C 5P. Most of the patients can recover with conservative treatment such as drug therapy and physical therapy, while those without significant improvement after 6 months of treatment may require surgical intervention such as foraminal decompression and nerve displacement. Conclusion: Currently, there has been some advancement in the etiology and intervention of C 5P. Nevertheless, further research is imperative to assess the timing of intervention and surgical protocol.

Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission.

BACKGROUND: Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped. MATERIALS AND METHODS: In vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically. RESULTS: We found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes. CONCLUSION: Collectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration.

High-level physical activity provides protection against all-cause mortality among U.S. adults with depression.

BACKGROUND: Regular physical activity (PA) offers numerous benefits, decreasing all-cause mortality (ACM) among the general population. However, its impact on individuals with depression remains unknown. The present study aimed to investigate the correlation between various PA levels and ACM among adult patients with depression in the United States. METHODS: Data from the National Health and Nutrition Examination Survey from 2007 to 2018, as well as relevant mortality data up to December 31, 2018 were extracted. 4850 adults with depression were incorporated into this cohort study. PA level was quantified based on weekly metabolic equivalent of task (MET-min/week) and categorized into four groups according to the Physical Activity Guidelines for Americans. Weighted Cox proportional-hazards models were leveraged to assess the association of different PA levels with ACM among adults with depression, and adjustments were made for various sociodemographic and health factors. RESULTS: Among the 4850 patients with depression, 503 deaths were noted over a median follow-up of 6.6 years. The weighted Cox regression analysis showed that participants with high-level PA (>1200 MET-min/week) had a markedly lower risk of ACM (HR = 0.48, 95 % CI 0.33 to 0.68) compared to those with no PA (0 MET-min/week). The benefit conferred by the high-level PA group (HR = 0.65, 95CI 0.45 to 0.94) remained significant (p < 0.05) after adjustment for other confounders. LIMITATIONS: PA and some covariates were assessed through self-reported questionnaires. CONCLUSION: High-level PA has the most pronounced effect on reducing ACM among adult patients with depression, which should be recognized in clinical and public health guidelines.

A real-world pharmacovigilance analysis of the FDA adverse event reporting system events for polatuzumab vedotin.

BACKGROUND: Polatuzumab vedotin is the first antibody-drug conjugate approved by the US Food and Drug Administration (FDA) for patients with diffuse large B-cell lymphoma. This study evaluated adverse events (AEs) associated with polatuzumab vedotin by data mining of the FDA Adverse Event Reporting System (FAERS). METHODS: This study included AEs registered in FAERS between 2019 Q2 and 2023 Q2. Four algorithms were used to quantify the signals of polatuzumab vedotin-associated AEs, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. RESULTS: A total of 7,609,450 reports were collected from the FAERS database, and 1,388 reports of polatuzumab vedotin were identified as primary suspected AEs. Polatuzumab vedotin-associated AEs involved 26 organ systems. According to the four algorithms, 108 significant disproportionality AEs were retained simultaneously. Unexpected significant AEs included gastrointestinal hemorrhage, ileus, gastrointestinal perforation, cholecystitis, hypogammaglobulinemia, hepatitis B reactivation, hypercalcemia, hydronephrosis, cystitis hemorrhagic, interstitial lung disease, and thrombophlebitis. The median time to onset of polatuzumab vedotin-associated AEs was 20 (interquartile range 4-56) days. CONCLUSIONS: Our study identified significant new AE signals for polatuzumab vedotin through real-world disproportionality analysis data and may provide additional evidence for risk identification of polatuzumab vedotin.

Exonuclease-iii -propelled DNAzyme cascade for sensitive and reliable cervical cancer related miRNA analysis.

MicroRNAs (miRNAs) can serve as biomarkers for early-diagnosis, therapy, and postoperative care of cervical cancer. Sensitive and reliable quantification of miRNA remains a huge challenge due to its low expressing levels and background interference. Herein, we propose a novel exonuclease-III (Exo-III)-propelled DNAzyme cascade for sensitive and high-efficient miRNA analysis. This method involves the engineering of compact DNAzyme hairpin probes, including the H1 probe and H2 probe. The H1 probe is designed with exposed analyte recognition subunits that can specifically recognize target miRNA. This recognition triggers two processes: Exo-iii-assisted target regeneration and successive substrate cleavage catalyzed by DNAzyme. The unique character of Exo-III that catalyzes removal of mononucleotides from the blunt or recessed 3'-OH termini of dsDNA confers the approach with a minimal background signal. The multiple signal cycles provided an abundant signal amplification and consequently, the method exhibited a low limit of detection of 3.12 fM, and a better specificity over several homologous miRNAs. In summary, this powerful Exo-III driven DNAzyme cascaded system offers broader and more adaptable methods for comprehending the activities of miRNA in various biological occurrences.

Evaluation of the modified MRI vertebral bone quality score for bone quality in lumbar degenerative disorders.

OBJECTIVE: The traditional VBQ scoring method may lead to overestimation due to the concentration of intravertebral fat and vascular structures in the posterior half of vertebral bodies, potentially resulting in false-positive outcomes. This study aims to modify the measurement method of VBQ score (Modified-VBQ) and evaluate its effectiveness in evaluating bone quality of lumbar degenerative diseases. METHODS: Retrospective analysis was conducted on clinical data from patients undergoing lumbar surgery for degenerative diseases between September 2022 and September 2023. Preoperative lumbar t1-weighted Magnetic resonance imaging was used for both modified and traditional VBQ scoring. Computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA) data were collected through the picture archiving and communication system. The effectiveness of the modified VBQ score was evaluated, considering P < 0.05 as statistically significant. RESULTS: The study included 212 patients, revealing a significant difference between the modified VBQ and VBQ scores (P < 0.0001). Notably, patients with a history of hyperlipidemia exhibited a significant difference between the two scores (P = 0.0037). The area under the ROC curve (AUC) for the modified VBQ was 0.86, surpassing the VBQ score (AUC = 0.74). Linear regression analysis demonstrated a moderate to strong correlation between the modified VBQ and DEXA T-score (r = - 0.49, P < 0.0001) and a high correlation with CT Hounsfield units (HU) values (r = - 0.60, P < 0.0001). CONCLUSION: The modified VBQ score provides a simple, effective, and relatively accurate means of assessing bone quality in lumbar degenerative diseases. Preoperative implementation of the modified VBQ score facilitates rapid screening for patients with abnormal bone quality.

CCT6A regulates cervical cancer cell glycolysis and proliferation under hypoxic conditions via the TCAB1/TERT.

OBJECTIVES: Cervical cancer is one of the most common female malignancies worldwide, a hypoxic microenvironment usually causes enhanced viability and glycolytic capacity of cervical cancer cells. The aim of this study was to investigate the association between chaperonin containing t-complex polypeptide 1 subunit 6A (CCT6A) and cell proliferation as well as hypoxic glycolysis. DESIGN: Bioinformatics analysis was conducted to explore the association between cervical cancer and its partner protein under hypoxic conditions, namely CCT6A. Subsequently, the expression of CCT6A was silenced, and the effects of CCT6A silencing on cervical cancer cell proliferation, cell cycle, glycolysis-related proteins, and telomerase activity were examined. MATERIALS, SETTING, METHODS: Bioinformatics analysis was performed to investigate the expression of CCT6A in cervical cancer under hypoxic conditions. The expression of CCT6A was silenced in cervical cancer cells, Hela and Siha, to study its effects on cell proliferation and hypoxic glycolysis. The localization of telomerase activity-related proteins, TCAB1 and TERT, was detected using immunofluorescence, and their interaction was assessed using immunoprecipitation. A cellular hypoxia model was established, and the products of the glycolysis reaction were detected. A nude mouse tumor model was constructed, and the changes in glycolysis-related proteins in tumor tissues were examined using western blot, while Ki67 expression in tumor tissues was evaluated by immunohistochemistry. RESULTS: Telomerase activity was found to be enhanced in CCT6A-silenced cervical cancer cells, along with an increase in telomerase cajal body protein 1 (TCAB1) and telomerase reverse tranase (TERT) protein binding associated with telomerase activity. Additionally, the proportion of cells in the Gap 2/mitosis (G2/M) stage and the 5-ethynyl-2'-deoxyuridine (EdU) positivity rate were decreased in CCT6A-silenced cells, indicating a reduction in cell proliferation. The expression of cell cycle-related proteins, including Cyclin E, CCNA2 and cyclin-dependent kinase 2 (CDK2), was suppressed. Furthermore, under a hypoxic environment, silencing CCT6A led to a significant reduction in cell viability and downregulation of glycolysis-related proteins, such as lactate dehydrogenase A (LDHA) and hexokinase 2 (HK2). Mechanistically, silencing CCT6A may reduce telomerase activity by inhibiting the TCAB1/TERT interaction. Additionally, TERT was found to activate the promoter region of the HK2 gene, and inhibition of TERT activity reduced the transcriptional level of HK2. LIMITATIONS: The study primarily explored the involvement of CCT6A in cervical cancer, yet it did not account for the myriad of other elements potentially influencing cell proliferation and glycolysis. It's essential to recognize that cervical cancer's etiology is multifaceted, shaped by an array of genetic variations, environmental influences, and protein interactions. CONCLUSIONS: Silencing CCT6A could effectively attenuate the upregulation of cell proliferation and glycolytic function mediated by TCAB1/TERT in cervical cancer cells.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

STUDY DESIGN: Observational study. OBJECTIVE: To assess the reproducibility and reliability of the system. BACKGROUND: The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. PATIENTS AND METHODS: Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. RESULTS: A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. CONCLUSIONS: The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

A Novel Cervical Sagittal Classification for Asymptomatic Population Based on Cluster Analysis.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To propose a novel cervical sagittal classification for asymptomatic people so as to deepen the understanding of cervical sagittal alignment. SUMMARY OF BACKGROUND DATA: Cervical spine sagittal morphology varies in people. There is a lack of widely-accepted cervical sagittal classification method. METHODS: In all, 183 asymptomatic subjects were included. A series of global and segmental cervical sagittal parameters were measured. Subjects with cervical lordosis (CL)<0 degrees were incorporated directly into the kyphosis (K) group. For subjects with CL ≥0 degrees, a two-step cluster analysis was used to arrive at the optimal number of clusters. The results of the expressions for the subtypes were derived by graphing. The 60 randomly selected lateral cervical spine films were evaluated by 4 spine surgeons at 4-week intervals using our classification method, the Toyama classification method and the Donk classification method. The 3 classification methods' reliability was expressed by the intra-group correlation coefficient (ICC), and convenience was expressed by the measuring time. Finally, the distribution of 4 subtypes was depicted, and sagittal parameters were compared among subtypes. RESULTS: Four subtypes of the cervical spine were suggested: Large lordosis (LL): CL≥-1.5×T1 slope (TS)+70°; Small lordosis (SL): -1.5×TS+50°≤CL<-1.5×TS+70°; Straight (S): 0°≤CL<-1.5×TS+50°; and K: CL<0°. The measuring time for our classification method was significantly less than the Toyama classification method (P<0.001). Our classification method showed high inter-observer reliability (ICC=0.856) and high to excellent intra-observer reliability (ICC between 0.851 and 0.913). SL was the most common type (37.7%). Men had more LL type and women had more S type and K type. The proportion of S and K increased with age. Cervical sagittal parameters were significantly different among the subtypes except for C4 vertebral body (VB) angle (P=0.546), C2-C7 SVA (P=0.628) and NT (P=0.816). CONCLUSIONS: We proposed a novel cervical sagittal classification for an asymptomatic population, which proved to be simple to implement with satisfactory reliability.

Age Is a Risk Factor for Gastroscopy-Assisted Capsule Endoscopy in Children.

BACKGROUND/AIMS: The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination. MATERIALS AND METHODS: A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination. RESULTS: A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05). CONCLUSION: A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.

Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study.

BACKGROUND & AIMS: Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study. METHODS: Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings. RESULTS: ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824-59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013-1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884-0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020-0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743-34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217-51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071-0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476-18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes. CONCLUSIONS: Some glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

Deep learning combining mammography and ultrasound images to predict the malignancy of BI-RADS US 4A lesions in women with dense breasts: a diagnostic study.

OBJECTIVES: The authors aimed to assess the performance of a deep learning (DL) model, based on a combination of ultrasound (US) and mammography (MG) images, for predicting malignancy in breast lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) US 4A in diagnostic patients with dense breasts. METHODS: A total of 992 patients were randomly allocated into the training cohort and the test cohort at a proportion of 4:1. Another, 218 patients were enrolled to form a prospective validation cohort. The DL model was developed by incorporating both US and MG images. The predictive performance of the combined DL model for malignancy was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The combined DL model was then compared to a clinical nomogram model and to the DL model trained using US image only and to that trained MG image only. RESULTS: The combined DL model showed satisfactory diagnostic performance for predicting malignancy in breast lesions, with an AUC of 0.940 (95% CI: 0.874-1.000) in the test cohort, and an AUC of 0.906 (95% CI: 0.817-0.995) in the validation cohort, which was significantly higher than the clinical nomogram model, and the DL model for US or MG alone ( P <0.05). CONCLUSIONS: The study developed an objective DL model combining both US and MG imaging features, which was proven to be more accurate for predicting malignancy in the BI-RADS US 4A breast lesions of patients with dense breasts. This model may then be used to more accurately guide clinicians' choices about whether performing biopsies in breast cancer diagnosis.

Differential diagnosis of breast mucinous carcinoma with an oval shape from fibroadenoma based on ultrasonographic features.

BACKGROUND: Approximately 50% of breast mucinous carcinomas (MCs) are oval and have the possibility of being misdiagnosed as fibroadenomas (FAs). We aimed to identify the key features that can help differentiate breast MC with an oval shape from FA on ultrasonography (US). METHODS: Seventy-six MCs from 71 consecutive patients and 50 FAs with an oval shape from 50 consecutive patients were included in our study. All lesions pathologically diagnosed. According to the Breast Imaging Reporting and Data System (BI-RADS), first, the ultrasonographic features of the MCs and FAs were recorded and a final category was assessed. Then, the differences in ultrasonographic characteristics between category 4 A (low-risk group) and category 4B-5 (medium-high- risk group) MCs were identified. Finally, other ultrasonographic features of MC and FA both with an oval shape were compared to determine the key factors for differential diagnosis. The Mann-Whitney test, χ2 test or Fisher's exact test was used to compare data between groups. RESULTS: MCs with an oval shape (81.2%) and a circumscribed margin (25%) on US were more commonly assessed in the low-risk group (BI-RADS 4 A) than in the medium-high-risk group (BI-RADS 4B-5) (20%, p < 0.001 and 0%, p = 0.001, respectively). Compared with those with FA, patients with MC were older, and tended to have masses with non-hypoechoic patterns, not circumscribed margins, and a posterior echo enhancement on US (p < 0.001, p < 0.001, and p = 0.003, respectively). CONCLUSION: The oval shape was the main reason for the underestimation of MCs. On US, an oval mass found in the breast of women of older age with non-hypoechoic patterns, not circumscribed margins, and a posterior echo enhancement was associated with an increased risk of being an MC, and should be subjected to active biopsy.

IiAGL6 participates in the regulation of stamen development and pollen formation in Isatis indigotica.

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.

Drug-Induced Acute Pancreatitis: A Real-World Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database.

Timely identification and discontinuation of culprit-drug is the cornerstone of clinical management of drug-induced acute pancreatitis (AP), but the comprehensive landscape of AP culprit-drugs is still lacking. To provide the current overview of AP culprit-drugs to guide clinical practice, we reviewed the adverse event (AE) reports associated with AP in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from 2004 to 2022, and summarized a potential AP culprit-drug list and its corresponding AE report quantity proportion. The disproportionality analysis was used to detect adverse drug reaction (ADR) signals for each drug in the drug list, and the ADR signal distribution was integrated to show the risk characteristic of drugs according to the ADR signal detection results. In the FAERS database, a total of 62,206 AE reports were AP-related, in which 1,175 drugs were reported as culprit-drug. On the whole, metformin was the drug with the greatest number of AE reports, followed by quetiapine, liraglutide, exenatide, and sitagliptin. Drugs used in diabetes was the drug class with the greatest number of AE reports, followed by immunosuppressants, psycholeptics, drugs for acid-related disorders, and analgesics. In disproportionality analysis, 595 drugs showed potential AP risk, whereas 580 drugs did not show any positive ADR signal. According to the positive-negative distribution of the ADR signal for drug classes, the drug class with the greatest number of positive drugs was antineoplastic agents. In this study, we provided the current comprehensive landscape of AP culprit-drugs from the pharmacovigilance perspective, which can provide reference information for clinical practice.

HHCDB: a database of human heterochromatin regions.

Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.

The transcription factor ELF4 alleviates inflammatory bowel disease by activating IL1RN transcription, suppressing inflammatory TH17 cell activity, and inducing macrophage M2 polarization.

Background: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells. Methods: Using the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment. Results: Bioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription. Conclusion: ELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD.

The Evolution of a Microstructure during Tempering and Its Influence on the Mechanical Properties of AerMet 100 Steel.

In order to provide guidance for furthering the balance of strength and toughness of AerMet 100 steel through tempering treatment, the effects of the tempering time on microstructure and mechanical properties are investigated. The microstructure evolution, especially M2C precipitates and austenite in AerMet 100 tempered at 482 °C for 1~20 h, was characterized, and its influences on the mechanical properties were studied. The tensile strength decreases gradually, the yield strength increases first and then decreases, and the fracture toughness KIC increases gradually with an increasing tempering time. The strength and toughness matching of AerMet 100 steel is achieved by tempering at 482 °C for 5~7 h. Without considering the martensitic size effect, the influence of the dislocation density on the tensile strength is more significant during tempering at 482 °C. The precipitation strengthening mechanism plays a dominant role in the yield strength when tempering for 5 h or less, and the combined influence of carbide coarsening and a sharp decrease in the dislocation density resulted in a significant decrease in tensile strength when tempering for 8 h or more. The fracture toughness KIC is primarily influenced by the reverted austenite, so that KIC increases gradually with the prolongation of the tempering time. However, a significant decrease in the dislocation density resulting from long-term tempering has a certain impact on KIC, giving rise to a decrease in the rising amplitude in KIC after tempering for 8 h or more.