Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China.

AIMS: Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations. METHODS: This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses. RESULTS: Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and BRAF gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates. CONCLUSION: p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.

Advancing Automatic Gastritis Diagnosis: An Interpretable Multilabel Deep Learning Framework for the Simultaneous Assessment of Multiple Indicators.

The evaluation of morphologic features, such as inflammation, gastric atrophy, and intestinal metaplasia, is crucial for diagnosing gastritis. However, artificial intelligence analysis for nontumor diseases like gastritis is limited. Previous deep learning models have omitted important morphologic indicators and cannot simultaneously diagnose gastritis indicators or provide interpretable labels. To address this, an attention-based multi-instance multilabel learning network (AMMNet) was developed to simultaneously achieve the multilabel diagnosis of activity, atrophy, and intestinal metaplasia with only slide-level weak labels. To evaluate AMMNet's real-world performance, a diagnostic test was designed to observe improvements in junior pathologists' diagnostic accuracy and efficiency with and without AMMNet assistance. In this study of 1096 patients from seven independent medical centers, AMMNet performed well in assessing activity [area under the curve (AUC), 0.93], atrophy (AUC, 0.97), and intestinal metaplasia (AUC, 0.93). The false-negative rates of these indicators were only 0.04, 0.08, and 0.18, respectively, and junior pathologists had lower false-negative rates with model assistance (0.15 versus 0.10). Furthermore, AMMNet reduced the time required per whole slide image from 5.46 to only 2.85 minutes, enhancing diagnostic efficiency. In block-level clustering analysis, AMMNet effectively visualized task-related patches within whole slide images, improving interpretability. These findings highlight AMMNet's effectiveness in accurately evaluating gastritis morphologic indicators on multicenter data sets. Using multi-instance multilabel learning strategies to support routine diagnostic pathology deserves further evaluation.

Study on the Relationship Between ß2 Macroglobulin, Small Density, Low-density Lipoprotein and Carotid Plaque Instability after Acute Thrombolysis in Patients with Ischemic Stroke.

Objective: Study the relationship between ß2 microglobulin, small density, low-density lipoprotein and carotid plaque instability after acute thrombolysis in ischemic stroke patients (IS). Methods: 319 patients with acute cerebral infarction who were treated by thrombolysis in the Department of Neurology, Chongming Branch of Shanghai Xinhua Hospital from January 2017 to May 2022 were included retrospectively. All subjects have undergone a carotid artery ultrasound examination for plaque. According to the ultrasound results, the subjects were divided into plaque-free group (94 cases), a stable plaque group (38 cases) and an unstable plaque group (187 cases). Use an automatic blood biochemical analyzer to detect routine indicators. At the same time, compare the differences of risk factors and biochemical indicators among the groups according to the demographic data of the patient's previous hospitalization. To further evaluate the related risk factors of the instability of carotid plaque in patients through the multivariate logistic regression analysis, the odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Analysis the predictive value of ß2 microglobulin and small density low density lipoprotein on the instability of carotid plaque in I.S. patients after acute thrombolysis through subject work characteristic curve (ROC). Results: Among 319 patients, 187 had unstable plaque accounting for 58.6% and 38 had stable plaque accounting for 11.9%, according to the comparison of general clinical data. Lymphocyte, neutrophil ratio, triglyceride, T3, Hcy, ß2 microglobulin has statistical significance in the presence or absence of plaque. Lymphocytes, small dense low-density lipoprotein, ß2 microglobulin have statistical significance in the stability of plaque (P < .05). Total cholesterol, hypertension, ß2 microglobulin and small density low-density lipoprotein may be independent risk factors of carotid plaque instability through multivariate logistic regression analysis (P < .05). The area under ROC curve showed that ß2 microglobulin AUC: 0.6388, P < .05, small density low-density lipoprotein AUC: 0.6086, P < .05, combined diagnosis AUC: 0.6924, P < .05. Conclusion: ß2 microglobulin and density low-density lipoprotein are independent risk factors of carotid artery plaque instability in I.S. patients after acute thrombolysis. Moreover, the sensibility and differential of combined diagnosis are higher, which has certain predictive value for the instability of carotid plaque in such patients.

Effect of total sleep deprivation on effective EEG connectivity for young male in resting-state networks in different eye states.

Background: Many studies have investigated the effect of total sleep deprivation (TSD) on resting-state functional networks, especially the default mode network (DMN) and sensorimotor network (SMN), using functional connectivity. While it is known that the activities of these networks differ based on eye state, it remains unclear how TSD affects them in different eye states. Therefore, we aimed to examine the effect of TSD on DMN and SMN in different eye states using effective functional connectivity via isolated effective coherence (iCoh) in exact low-resolution brain electromagnetic tomography (eLORETA). Methods: Resting-state electroencephalogram (EEG) signals were collected from 24 male college students, and each participant completed a psychomotor vigilance task (PVT) while behavioral data were acquired. Each participant underwent 36-h TSD, and the data were acquired in two sleep-deprivation times (rested wakefulness, RW: 0 h; and TSD: 36 h) and two eye states (eyes closed, EC; and eyes open, EO). Changes in neural oscillations and effective connectivity were compared based on paired t-test. Results: The behavioral results showed that PVT reaction time was significantly longer in TSD compared with that of RW. The EEG results showed that in the EO state, the activity of high-frequency bands in the DMN and SMN were enhanced compared to those of the EC state. Furthermore, when compared with the DMN and SMN of RW, in TSD, the activity of DMN was decreased, and SMN was increased. Moreover, the changed effective connectivity in the DMN and SMN after TSD was positively correlated with an increased PVT reaction time. In addition, the effective connectivity in the different network (EO-EC) of the SMN was reduced in the ß band after TSD compared with that of RW. Conclusion: These findings indicate that TSD impairs alertness and sensory information input in the SMN to a greater extent in an EO than in an EC state.

A newly identified lncRNA lnc000100 regulates proliferation and differentiation of cattle skeletal muscle cells.

Cattle skeletal muscle development is a complex and highly coordinated biological process mediated by a series of myogenic regulators, which plays a critical role in beef yield and quality. Long non-coding RNAs (lncRNAs) have been shown to regulate skeletal muscle development. However, the molecular mechanism by which lncRNAs regulate skeletal muscle development is largely unknown. We performed transcriptome analysis of muscle tissues of adult and embryo Angus cattle to investigate the mechanism by which lncRNA regulates skeletal muscle development between adult and embryo cattle. A total of 37,115 candidate lncRNAs were detected, and a total of 1,998 lncRNAs were differentially expressed between the muscle tissue libraries of adult and embryo cattle, including 1,229 up-regulated lncRNAs and 769 down-regulated lncRNAs (adult cattle were the control group). We verified the expression of 7 differentially expressed lncRNAs by quantitative real-time PCR (RT-qPCR), and analysed the tissue expression profile of lnc000100, which is down-regulated in the longest dorsal muscle during foetal life and which is highly specifically expressed in muscle tissue. We found that the interference of lnc000100 significantly inhibited cell proliferation and promoted cell differentiation. Lnc000100 was located in the nucleus by RNA-FISH. Our research provides certain resources for the analysis of lncRNA regulating cattle skeletal muscle development, and may also provide new insights for improving beef production and breed selection.

Identification of lncRNAs associated with muscle development and skeletal muscle disease that are differentially expressed between embryo and adult cattle. We identified 1,998 differentially expressed lncRNAs between the muscle tissue libraries of adult and embryo. GO analysis showed that these lncRNAs were involved in muscle development.Construction of co-expression networks and competitive endogenous networks related to muscle development. We constructed the co-expression networks and lncRNA-miRNA-mRNA interaction networks of four differentially expressed lncRNAs.A newly identified lncRNA lnc000100 promoted myoblast proliferation and inhibited myoblast differentiation during muscle development. GO analysis showed that lnc000100 was associated with muscle development (such as muscle structure development, etc.) and skeletal muscle diseases (such as muscle hypertrophy, etc.). FISH analysis suggests that lnc000100 is localized in the nucleus and may regulate muscle development at the transcriptional/post-transcriptional level.

Synthesis of Cationic Biphen[4, 5]arenes as Biofilm Disruptors.

Since bacteria in biofilms are inherently resistant to antibiotics and biofilm-associated infections pose a serious threat to global public health, new therapeutic agents and schemes are urgently needed to meet clinical requirements. Here two quaternary ammonium-functionalized biphen[n]arenes (WBPn, n=4, 5) were designed and synthesized with excellent anti-biofilm potency. Not only could they inhibit the assembly of biofilms, but also eradicate intractable mature biofilms formed by Gram-positive S. aureus and Gram-negative E. coli bacterial strains. Moreover, they could strongly complex a conventional antibiotic, cefazolin sodium (CFZ) with complex stability constants of (7.41±0.29)×104  M-1 for CFZ/WBP4 and (4.98±0.49)×103  M-1 for CFZ/WBP5. Combination of CFZ by WBP4 and WBP5 synergistically enhanced biofilm eradication performance in vitro and statistically improved healing efficacy on E. coli-infected mice models, providing a novel supramolecular strategy for combating biofilm-associated infections.

A Biocompatible Liquid Pillar[n]arene-Based Drug Reservoir for Topical Drug Delivery.

Advanced external preparations that possess a sustained-release effect and integrate few irritant elements are urgently needed to satisfy the special requirements of topical administration in the clinic. Here, a series of liquid pillar[n]arene-bearing varying-length oligoethylene oxide chains (OEPns) were designed and synthesized. Following rheological property and biocompatibility investigations, pillar[6]arene with triethylene oxide substituents (TEP6) with satisfactory cavity size were screened as optimal candidate compounds. Then, a supramolecular liquid reservoir was constructed from host-guest complexes between TEP6 and econazole nitrate (ECN), an external antimicrobial agent without additional solvents. In vitro drug-release studies revealed that complexation by TEP6 could regulate the release rate of ECN and afford effective cumulative amounts. In vivo pharmacodynamic studies confirmed the formation of a supramolecular liquid reservoir contributed to the accelerated healing rate of a S. aureus-infected mouse wound model. Overall, these findings have provided the first insights into the construction of a supramolecular liquid reservoir for topical administration.

Host-guest synergistic enhancement of antibacterial effect by a supramolecular strategy.

A supramolecular synergistic antibacterial strategy involving direct complexation of a commercial antibacterial agent, azelaic acid (AzA) by a cationic pillar[5]arene (WP5A) is described. The formation of AzA/WP5A complex could exert synergistic antibacterial effect, leading to promote wound healing efficacy and reduce bacterial burden on S. aureus-infected mice models.

Enhanced effective connectivity from the middle frontal gyrus to the parietal lobe is associated with impaired mental rotation after total sleep deprivation: An electroencephalogram study.

Sleep deprivation impairs cognitive functions, including attention, memory, and decision-making. Studies on the neuro-electro-physiological mechanisms underlying total sleep deprivation (TSD) that impairs spatial cognition are limited. Based on electroencephalogram (EEG) and Exact Low Resolution Brain Electromagnetic Tomography (eLORETA), this study focused on the effects of TSD on mental rotation and the cognitive neural mechanisms underlying its damage. Twenty-four healthy college students completed mental rotation tasks while resting and after 36 h of TSD; their EEG data were simultaneously recorded. The amplitude of P300 component associated with mental rotation was observed and localized through source reconstruction, while changes in effective connectivity between multiple brain regions associated with mental rotation cognitive processing were calculated using isolated effective coherence (iCoh) of eLORETA. Compared with the baseline before TSD, the amplitude of the P300 component related to mental rotation decreased. The task-state data of P300 were localized to the source of the difference in ERP current density, and it was found that the brain regions related to the difference in the decrease in P300 amplitude included the superior parietal lobule, precuneus, prefrontal lobe, and other related regions. Effective connectivity analysis found that TSD enhanced the effective connectivity from the left middle frontal gyrus to the left superior parietal lobule, left inferior parietal lobule, and left precuneus under the identical condition. Pearson correlation analysis showed a positive correlation between the decrease in accuracy of mental rotation and increase in effective connectivity. Thus, our study suggests that TSD impairs the ability of the mental rotation, showing a decrease in P300 amplitude and an enhanced effective connectivity between the middle frontal gyrus and the parietal lobe in the task state.

Supramolecular Detoxification of Macromolecular Biotoxin through the Complexation by a Large-Sized Macrocycle.

Biotoxins are diverse, complex, and hypertoxic, ultimately serving as grave and lasting menaces to humanity. Here, it is aimed to introduce a new detoxification methodology for macromolecular biotoxin through complexation by a very large macrocycle. A 25-mer peptide isolated from Lycosa erythrognatha spider venom (LyeTxI) is selected as the model macromolecular biotoxin. Quaterphen[4]arene, with a side length of ≈1.6 nm, has a sufficient cavity to bind LyeTxI. Hence, the water-soluble derivative of Quaterphen[4]arene (H) is designed and synthesized. H exhibits an overall host-guest complexation toward LyeTxI, resulting in a considerably high association constant of (7.01 ± 0.18) × 107  m-1 . This encapsulation of peptide is interesting as traditional macrocycles can only engulf the amino acid residues of peptides due to their limited cavity size. In vitro assay verifies that complexation by H inhibits the interactions of LyeTxI with cell membranes, thereby reducing its cytotoxicity, suppressing hemolysis, and decreasing the release of lactate dehydrogenase. Notably, the intravenous administration of H has a significant therapeutic effect on LyeTxI-poisoned mice, alleviating inflammation and tissue damage, and markedly improving the survival rate from 10% to 80%. An efficient and potentially versatile approach is provided to detoxify macromolecular biotoxins, with giant macrocycle serving as an antidote.

Complexation of specific residues by carboxylatopillar[6]arene for improving the zymolytic stability of arginine-containing peptides.

A general strategy for improving the zymolytic stability against proteases is reported. Carboxylatopillar[6]arene (CP6A) could effectively bind arginine and arginine-containing peptides, thereby improving the stability of angiotensin peptides in the presence of trypsin by the complexation of the side chain of the arginine residue.

Supramolecular Drug Delivery System from Macrocycle-Based Self-Assembled Amphiphiles for Effective Tumor Therapy.

Intelligent drug delivery systems (DDSs) that can improve therapeutic outcomes of antitumor agents and decrease their side effects are urgently needed to satisfy special requirements of treatment of malignant tumors in clinics. Here, the fabrication of supramolecular self-assembled amphiphiles based on the host-guest recognition between a cationic water-soluble pillar[6]arene (WP6A) host and a sodium decanesulfonate guest (G) is reported. The chemotherapeutic agent doxorubicin hydrochloride (DOX) can be encapsulated into the formed vesicle (G/WP6A) to construct supramolecular DDS (DOX@G/WP6A). WP6A affords strong affinities to G to avoid undesirable off-target leakage during delivery. Nanoscaled DOX@G/WP6A is capable of preferentially accumulating in tumor tissue via enhanced permeability and retention (EPR) effect. After internalization by tumor cells, the abundant adenosine triphosphate (ATP) binds competitively with WP6A to trigger the disintegration of self-assembled vesicles with the ensuing release of DOX. In vitro and in vivo research confirmed that DOX@G/WP6A is not only able to promote antitumor efficacy but also reduce DOX-related systemic toxicity. The above favorable findings are ascribed to the formation of ternary self-assembly, which profits from the combination of the factors of the EPR effect and the ATP-triggered release.

Measurement of Chladni Mode Shapes with an Optical Lever Method.

Quantitatively determining the Chladni pattern of an elastic plate is of great interest in both physical science and engineering applications. In this paper, a method of measuring mode shapes of a vibrating plate based on an optical lever method is proposed. Three circular acrylic plates were employed in the measurement under different center harmonic excitations. Different from a traditional method, only an ordinary laser pen and a light screen made of ground glass are employed in this novel approach. The approach is as follows: the laser pen projects a beam to the vibrating plate perpendicularly, and then the beam is reflected to the light screen in the distance, on which a line segment made of the reflected spot is formed. Due to the principle of vision persistence, the light spot could be read as a bright straight line. The relationship between the slope of the mode shape, length of the light spot and the distance of the vibrating plate and the light screen can be obtained with algebraic operations. Then the mode shape can be determined by integrating the slope distribution with suitable boundary conditions. The full-field mode shapes of Chladni plate could also be determined further in such a simple way.

Quantitative evaluation of tissue stiffness around lesion by sound touch elastography in the diagnosis of benign and malignant breast lesions.

The purpose of our study is to assess the diagnostic performance of quantitative evaluation of tissue stiffness around lesion by Sound Touch Elastography (STE) in distinguishing between benign and malignant breast lesions. A total number of 160 breast lesions from 160 female patients were examined by STE. Resona 7 was equipped with "shell" function to measure elastic modulus values of tissue in the region of surrounding lesion quantitatively. The contours of the lesion were required to be delineated. The elastic modulus values of tissue in the region of 1mm, 2mm, and 3mm outside the boundary were acquired. The elastic modulus values included maximum elastic modulus (Emax), mean elastic modulus (Emean), minimum elastic modulus (Emin), and elastic modulus standard deviation (Esd). All lesions were confirmed by histopathology. We compared the differences of the above elastic modulus values between benign and malignant groups. Receiver operating characteristic (ROC) curve was drawn with the histological diagnostic results as the gold standard. Sensitivity and specificity were calculated to evaluate the diagnostic performance of STE. Operator consistency was also analyzed. Among the 160 lesions, 100 (62.5%) were benign and 60 (37.5%) were malignant. In the region of 1mm, 2mm, and 3mm surrounding the lesion, Emax, Emean, and Esd of malignant group were significantly higher than those of the benign group (all P<0.05). When the "shell" was 3mm, Emax had the highest AUROC value (AUROC = 0.998). Regarding the measurement of elastic modulus values, all the intra-class correlation coefficient (ICC) values of the inter-operator consistency were greater than 0.75 for Emax, Emean, and Esd. Therefore, quantitative evaluation of tissue stiffness around lesion by STE has the potential to distinguish between benign and malignant breast lesions.