Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases.

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Covalently Bonded Heterostructures with Mixed-Dimensional Carbons for Suppressing Mechanochemical Wear of Diamond under Heavy Loads.

Diamond is widely acknowledged as the hardest naturally occurring material. Nevertheless, when exposed to friction against ferrous metals, it is prone to graphitization or amorphization, which limits the utilization of its extremely high hardness and wear resistance. These issues have persisted for decades without an effective solution. Here, we report that a covalently bonded heterostructure with mixed-dimensional carbons as a high-performance solid lubricant could effectively reduce diamond surface friction and mechanochemical wear with excellent load capacity and durability. When subjected to dry friction and heavy loads (20-150 N), the heterostructure exhibited a notable improvement over pristine diamond with reduced friction coefficients and relative wear rates by 22-45 and 67-91%, respectively. Especially under a 20 N load, the relative wear rate was an order of magnitude lower than that of pristine diamond. Additionally, experiments and molecular dynamics simulations revealed that the heterostructure integrated the outstanding properties of diamond (three-dimensional (3D)), nanographite (3D), and graphene (two-dimensional (2D)), resulting in improved lubrication and antiwear performance that could not be achieved by the individual carbon materials. The findings in this work will be beneficial to overcome the ferrous metal forbidden zone of diamond and are expected to expand the applications of engineered diamond surfaces and graphite/graphene in tribology, mechanics, and electronic fields.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Epidemiology of Ocular Thelaziosis in Domestic Dogs in Beijing.

Thelazia callipaeda is a zoonotic parasitic nematode that lives in the ocular conjunctival sac of domestic and wild carnivores, lagomorphs, and humans, with Phortica spp. as its intermediate host. At present, the important role that domestic dogs play in thelaziosis has been studied in many countries. However, Beijing, which is the first city in China to experience human thelaziosis, has not yet conducted a comprehensive epidemiological analysis of the disease. In this study, we analyzed risk factors (region, season, age, sex, breed, size, living environment, diet, country park travel history, immunization history, anthelmintic treatment history, and ocular clinical symptoms) associated with the prevalence of thelaziosis in domestic dogs in Beijing. The overall prevalence of T. callipaeda in the study area was 3.17% (102/3215 domestic dogs; 95% CI 2.57-3.78%). The results of the risk factor analysis showed that thelaziosis in domestic dogs from Beijing was significantly correlated with regional distribution, seasonal distribution, country park travel history, and anthelmintic treatment history (p < 0.05). In summer and autumn, domestic dogs living in mountainous areas, with a history of country park travel and without deworming were 4.164, 2.382, and 1.438 times more infected with T. callipaeda than those living in plain areas without a history of country park travel and with a history of deworming (OR = 4.164, OR = 2.382, OR = 1.438, respectively). T. callipaeda-infected domestic dogs did not always show any ocular clinical symptoms, while symptomatic domestic dogs were mainly characterized by moderate symptoms. The results indicate that in summer and autumn, preventive anthelmintic treatment should be strengthened for domestic dogs with a country park travel history or those living in mountain areas. At the same time, we should be vigilant about taking domestic dogs to play in country parks or mountainous areas during summer and autumn because this may pose a potential risk of the owner being infected with T. callipaeda.

Enhancing the Efficiency of a Radiation Oncology Department Using Electronic Medical Records: Protocol for Preparing Radiotherapy.

BACKGROUND: Electronic medical records (EMRs) streamline medical processes, improve quality control, and facilitate data sharing among hospital departments. They also reduce maintenance costs and storage space needed for paper records, while saving time and providing structured data for future research. OBJECTIVE: This study aimed to investigate whether the integration of the radiation oncology information system and the hospital information system enhances the efficiency of the department of radiation oncology. METHODS: We held multidisciplinary discussions among physicians, physicists, medical radiation technologists, nurses, and engineers. We integrated paper records from the radiation oncology department into the existing hospital information system within the hospital. A new electronic interface was designed. A comparison was made between the time taken to retrieve information from either the paper records or the EMRs for radiation preparation. A total of 30 cases were randomly allocated in both the old paper-based system and the new EMR system. The time spent was calculated manually at every step during the process, and we performed an independent 1-tailed t test to evaluate the difference between the 2 systems. RESULTS: Since the system was launched in August 2020, more than 1000 medical records have been entered into the system, and this figure continues to increase. The total time needed for the radiation preparation process was reduced from 286.8 minutes to 154.3 minutes (P<.001)-a reduction of 46.2%. There was no longer any need to arrange for a nurse to organize the radiotherapy paper records, saving a workload of 16 hours per month. CONCLUSIONS: The implementation of the integrated EMR system has resulted in a significant reduction in the number of steps involved in radiotherapy preparation, as well as a decrease in the amount of time required for the process. The new EMR system has provided numerous benefits for the department, including a decrease in workload, a simplified workflow, and conserving more patient data within a confined space.

Facile Preparation of a Photo-Cross-Linked Silk Fibroin-Poly Ionic Liquid Hydrogel with Antifreezing and Ion Conductive Properties.

The silk fibroin (SF)/ionic liquid (IL) based hydrogel is a kind of remarkable substrate for flexible devices because of its subzero-temperature elasticity, electrical conductivity, and water retention, although the procedure of the gelation is considered complex and time-consuming. In this work, we introduced an approximate method for the development of novel photo-cross-linked SF/IL hydrogel, that is, SF-IMA/PIL hydrogel via the modification of silk fibroin chain with 2-isocyanatoethyl methacrylate (SF-IMA) in a certain ionic liquid with an unsaturated double bond. The chemical cross-linking between methacrylated SF and IL was triggered by UV light, while the physical cross-linking of the hydrogel was attributed to the ß-sheet formation of SF in SF-IMA/IL mixed solution. In addition to being a UV-induced three-dimensional (3D) printable one, the SF-IMA/PIL hydrogel performed significant ionic conductivity between room temperature and -50 °C and water retention within a wide range of relative humidity, which were the featured advantages as the ionic liquid involved. Moreover, the static and dynamic mechanical tests demonstrated that the hydrogel reserved its great elasticity at -50 °C and displayed its stiffness transition temperatures between -100 and -70 °C.

[Imaging study on thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis].

OBJECTIVE: To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS) and the difference of physiological curvature between different types of scoliosis. METHODS: A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021. The patients were divided into normal group and scoliosis group. The normal group was composed of 179 patients, 79 males and 100 females, aged 10 to 18 years old with an average of (12.84±2.10) years old, with cobb agle less than 10 degrees. The scoliosis group was composed of 126 patients, 33 males and 93 females, aged 10 to 18 years old with an average of (13.92±2.20) years old. The gender, age, Risser sign, thoracic kyphosis(TK) and lumbar lordosis(LL) in 2 groups were compared, and the TK and LL were also compared between different genders, different degrees of scoliosis and different segments of scoliosis. RESULTS: The female ratio(P=0.001) and age (P<0.001) in scoliosis group were higher than them in normal group; the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038). TK was significantly smaller in scoliosis group than in normal group(P<0.001), but there was no significant difference in LL between the 2 groups(P=0.147). There were no significant difference in TK and LL between male and female. The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P<0.05), but there was no significant difference in LL between mild and moderate patients(P>0.05). The TK and LL in different segments scoliosis were not found significant difference. CONCLUSION: The physiological curvature of thoracic and lumbar spine is independent of gender. The thoracic physiological curvature becomes smaller in AIS patients, but lumbar curvature remains unchanged. The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients, but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent. The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative anterior spinal overgrowth, and the specific detailed mechanism needs to be further studied.

Evaluation of Key Molecular Markers in Adult Diffuse Gliomas Based on a Novel Combination of Diffusion and Perfusion MRI and MR Spectroscopy.

BACKGROUND: Preoperative identification of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status could help clinicians select the optimal therapy in patients with diffuse glioma. Although, the value of multimodal intersection was underutilized. PURPOSE: To evaluate the value of quantitative MRI biomarkers for the identification of IDH mutation and 1p/19q codeletion in adult patients with diffuse glioma. STUDY TYPE: Retrospective. POPULATION: Two hundred sixteen adult diffuse gliomas with known genetic test results, divided into training (N = 130), test (N = 43), and validation (N = 43) groups. SEQUENCE/FIELD STRENGTH: Diffusion/perfusion-weighted-imaging sequences and multivoxel MR spectroscopy (MRS), all 3.0 T using three different scanners. ASSESSMENT: The apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) of the core tumor were calculated to identify IDH-mutant and 1p/19q-codeleted statuses and to determine cut-off values. ADC models were built based on the 30th percentile and lower, CBV models were built based on the 75th centile and higher (both in five centile steps). The optimal tumor region was defined and the metabolite concentrations of MRS voxels that overlapped with the ADC/CBV optimal region were calculated and added to the best-performing diagnostic models. STATISTICAL TESTS: DeLong's test, diagnostic test, and decision curve analysis were performed. A P value <0.05 was considered to be statistically significant. RESULTS: Almost all ADC models achieved good performance in identifying IDH mutation status, among which ADC_15th was the most valuable parameter (threshold = 1.186; Youden index = 0.734; AUC_train = 0.896). The differential power of CBV histogram metrics for predicting 1p/19q codeletion outperformed ADC histogram metrics, and the CBV_80th-related model performed best (threshold = 1.435; Youden index = 0.458; AUC_train = 0.724). The AUCs of ADC_15th and CBV_80th models in the validation set were 0.857 and 0.733. These models tended to improve after incorporation of N-acetylaspartate/total_creatine and glutamate-plus-glutamine/total_creatine, respectively. DATA CONCLUSION: The intersection of ADC-, CBV-based histogram and MRS provide a reliable paradigm for identifying the key molecular markers in adult diffuse gliomas. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

The induced and intrinsic resistance of Escherichia coli to sanguinarine is mediated by AcrB efflux pump.

IMPORTANCE: The use of plant extracts is increasing as an alternative to synthetic compounds, especially antibiotics. However, there is no sufficient knowledge on the mechanisms and potential risks of antibiotic resistance induced by these phytochemicals. In the present study, we found that stable drug resistant mutants of E. coli emerged after repetitive exposure to sanguinarine and demonstrated that the AcrB efflux pump contributed to the emerging of induced and intrinsic resistance of E. coli to this phytochemical. Our results offered some insights into comprehending and preventing the onset of drug-resistant strains when utilizing products containing sanguinarine.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Development and External Validation of an MRI-based Radiomics Nomogram to Distinguish Circumscribed Astrocytic Gliomas and Diffuse Gliomas: A Multicenter Study.

RATIONALE AND OBJECTIVES: The 5th edition of the World Health Organization classification of tumors of the Central Nervous System (WHO CNS) has introduced the term "diffuse" and its counterpart "circumscribed" to the category of gliomas. This study aimed to develop and validate models for distinguishing circumscribed astrocytic gliomas (CAGs) from diffuse gliomas (DGs). MATERIALS AND METHODS: We retrospectively analyzed magnetic resonance imaging (MRI) data from patients with CAGs and DGs across three institutions. After tumor segmentation, three volume of interest (VOI) types were obtained: VOItumor and peritumor, VOIwhole, and VOIinterface. Clinical and combined models (incorporating radiomics and clinical features) were also established. To address imbalances in training dataset, Synthetic Minority Oversampling Technique was employed. RESULTS: A total of 475 patients (DGs: n = 338, CAGs: n = 137) were analyzed. The VOIinterface model demonstrated the best performance for differentiating CAGs from DGs, achieving an area under the curve (AUC) of 0.806 and area under the precision-recall curve (PRAUC)of 0.894 in the cross-validation set. Using analysis of variance (ANOVA) feature selector and Support Vector Machine (SVM) classifier, seven features were selected. The model achieved an AUC and AUPRC of 0.912 and 0.972 in the internal validation dataset, and 0.897 and 0.930 in the external validation dataset. The combined model, incorporating interface radiomics and clinical features, showed improved performance in the external validation set, with an AUC of 0.94 and PRAUC of 0.959. CONCLUSION: Radiomics models incorporating the peritumoral area demonstrate greater potential for distinguishing CAGs from DGs compared to intratumoral models. These findings may hold promise for evaluating tumor nature before surgery and improving clinical management of glioma patients.

MRI characteristics of H3 G34-mutant diffuse hemispheric gliomas and possible differentiation from IDH-wild-type glioblastomas in adolescents and young adults.

OBJECTIVE: H3 G34-mutant diffuse hemispheric gliomas (G34m-DHGs) are rare and constitute a new infiltrating brain tumor entity whose characteristics require elucidation, and their difference from isocitrate dehydrogenase-wild-type glioblastomas (IDH-WT-GBMs) needs to be clarified. In this study, the authors report the demographic, clinical, and neuroradiological features of G34m-DHG and investigate the capability of quantitative MRI features in differentiating them. METHODS: Twenty-three patients with G34m-DHG and 30 patients with IDH-WT-GBM were included in this retrospective study. The authors reviewed the clinical, radiological, and molecular data of G34m-DHGs and compared their neuroimaging features with those of IDH-WT-GBMs in adolescents and young adults. Visually Accessible Rembrandt Images (VASARI) features were extracted, and the Kruskal-Wallis test was performed. A logistic regression model was constructed to evaluate the diagnostic performance for differentiating between G34m-DHG and IDH-WT-GBM. Subsequently, FeAture Explorer (FAE) was used to generate the machine learning pipeline and select important radiomics features that had been extracted with PyRadiomics. Estimates of the performance were supplied by metrics such as sensitivity, specificity, accuracy, and area under the curve (AUC). RESULTS: The mean age of the 23 patients with G34m-DHG was 23.7 years (range 11-45 years), younger than the mean age of patients with IDH-WT-GBM (30.96 years, range 5-43 years). All tumors were hemispheric. Most cases were immunonegative for ATRX (95%) and Olig2 (100%), were immunopositive for p53 (95%), and exhibited MGMT promoter methylation (81%). The radiological presentations of G34m-DHG were different from those of IDH-WT-GBM. The majority of the G34m-DHGs were in the frontal, parietal, and temporal lobes and demonstrated no or only faint contrast enhancement (74%), while IDH-WT-GBMs were mostly seen in the frontal lobe and showed marked contrast enhancement in 83% of cases. The FAE-generated model, based on radiomics features (AUC 0.925) of conventional MR images, had better discriminatory performance between G34m-DHG and IDH-WT-GBM than VASARI feature analysis (AUC 0.843). CONCLUSIONS: G34m-DHGs most frequently occur in the frontal, parietal, and temporal lobes in adolescent and young adults and are associated with radiological characteristics distinct from those of IDH-WT-GBMs. Successful identification can be achieved by using either VASARI features or radiomics signatures, which may contribute to prognostic evaluation and assist in clinical settings.

Edible pueraria lobata-derived exosome-like nanovesicles ameliorate dextran sulfate sodium-induced colitis associated lung inflammation through modulating macrophage polarization.

BACKGROUND: Inflammatory bowel diseases (IBD), such as severe colitis, are associated with the development of lung inflammation and tissue damage. Pueraria lobata (P. lobata) plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. PURPOSE: To investigate the effects of the P. lobata-derived exosomes-like nanovesicles (PLDENs) on colitis and their role in the lung inflammatory response. METHODS: In this study, we investigated the effects of PLDENs on the dextran sulfate sodium (DSS)-induced colitis and explored the mechanisms by forming the gut-lung axis. PLDENs were characterized by mass spectrometry-based proteomic analysis. RESULTS: The results showed that PLDENs had significant preventive effects in DSS-induced colitis and pathological changes in colons in a dose-dependent manner. Simultaneously, the treatment of PLDENs could effectively reduce inflammatory changes in the lung. PLDENs could selectively regulate the composition of gut microbiota. CONCLUSION: These data suggested that the treatment of PLDENs could 'attenuate DSS-induced colitis and lung inflammation, providing an efficacious supplement for reducing co-morbidities in IBD patients.

Association between inflammatory bowel disease and risk of stroke: a systematic review and meta-analysis of cohort studies.

Background/objectives: Recently, four meta-analyses have explored the association between inflammatory bowel disease (IBD) and the risk of stroke. These studies have demonstrated that people with IBD may be at an increased risk of stroke. However, some limitations such as high heterogeneity and the lack of uniformity in the types of research, especially the reuse of some sample sizes, cannot be neglected. These factors reduce the credibility of their research conclusions. Therefore, we conducted a meta-analysis to explore this possible association. Methods: PubMed, Embase, and Web of Science were searched from inception to 30 June 2023. A random effects model with the generic inverse variance method was used in this meta-analysis. The Review Manager software was used to obtain all relative risks (RRs) and their 95% confidence intervals (CIs). Publication bias was tested, and sensitivity and subgroup analyses were conducted to explore possible heterogeneities. Results: This meta-analysis included 12 cohort studies (involving 4,495,055 individuals). Meta-analysis of these data has shown that IBD was associated with an increased risk of stroke (RR = 1.19, 95%CI:1.14-1.24, p < 0.00001). Our results were stable and robust in subgroup and sensitivity analyses. Conclusions: Our results suggest that IBD is associated with an increased risk of stroke. To reduce the incidence of stroke, patients with IBD are encouraged to undergo stroke risk assessments, especially for young female patients; assessing the risk of ischemic stroke is of particular importance. Prospective studies considering stroke subtypes, IBD severity and treatments, regions, and other confounding factors are needed to further explore the nature of each association. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022373656.

Emphysematous thrombophlebitis caused by a misplaced central venous catheter: A case report.

BACKGROUND: Central venous catheters (CVCs) often cause life-threatening complications, especially CVC-related bloodstream infection (CVC-BSI) and catheter-related thrombosis (CRT). Here, we report an unusual case of misplaced CVC-induced emphysematous thrombophlebitis, a rare but potentially lethal form of CRT and CVC-BSI characterized by both thrombosis and gas formation. CASE SUMMARY: A 48-year-old male presented to the emergency room of a local hospital with sudden-onset headache and coma for 4 h. Computed tomography (CT) revealed right basal ganglia hemorrhage, so emergency decompressive craniotomy was performed and a CVC was inserted through the right subclavian vein for fluid resuscitation during anesthesia. Two days later, the patient was transferred to the intensive care unit of our hospital for further critical care. On day 9 after CVC insertion, the patient suddenly developed fever and hypotension. Point-of-care ultrasound (POCUS) demonstrated thrombosis and dilatation of the right internal jugular vein (IJV) filled with thrombosis. Ultrasonography also revealed that the CVC tip had been misplaced into the IJV and was surrounded by gas bubbles, which manifested as hyperechoic lines with dirty shadowing and comet-tail artifacts. Further CT scan confirmed air bubbles surrounding the CVC in the right neck. The final diagnosis was septic emphysematous thrombophlebitis induced by a misplaced CVC and ensuing septic shock. The responsible CVC was removed immediately. The patient received fluid resuscitation, intravenous noradrenaline, and a 10-d ultra-broad spectrum antibiotic treatment to combat septic shock. Both CVC and peripheral venous blood cultures yielded methicillin-resistant Staphylococcus cohnii. The patient was gradually weaned off vasopressors and the symptoms of redness and swelling in the right neck subsided within 7 d. CONCLUSION: Emphysematous thrombophlebitis is a fulminant and life-threatening CVC-BSI associated with thrombosis and gas formation in the vein. A misplaced CVC may facilitate the development of emphysematous thrombophlebitis. POCUS can easily identify the artifacts produced by gas and thrombosis, facilitating rapid diagnosis at the bedside.

Tool Wear State Recognition Based on One-Dimensional Convolutional Channel Attention.

Tool wear state recognition is an important part of tool condition monitoring (TCM). Online tool wear monitoring can avoid wasteful early tool changes and degraded workpiece quality due to later tool changes. This study incorporated an attention mechanism implemented by one-dimensional convolution in a convolutional neural network for improving the performance of the tool wear recognition model (1DCCA-CNN). The raw multichannel cutting signals were first preprocessed and three time-domain features were extracted to form a new time-domain sequence. CNN was used for deep feature extraction of temporal sequences. A novel 1DCNN-based channel attention mechanism was proposed to weigh the channel dimensions of deep features to enhance important feature channels and capture key features. Compared with the traditional squeeze excitation attention mechanism, 1DCNN can enhance the information interaction between channels. The performance of the model was validated on the PHM2010 public cutting dataset. The excellent performance of the proposed 1DCCA-CNN was verified by the improvement of 4% and 5% compared to the highest level of existing research results on T1 and T3 datasets, respectively.

Identification and verification of m6A-related miRNAs correlated with prognosis and immune microenvironment in colorectal cancer.

It's well known that N6-methyladenosine (m6A) modification is the most abundant modification in multiple RNA species. miRNAs play important roles in m6A modification and are closely related with occurrence and development of colorectal cancer (CRC). Thus, the aim of this study was to identify the prognostic value of m6A-related miRNAs and explore the correlation between the miRNAs and immune microenvironment in CRC. The differentially expressed m6A regulators and differentially expressed miRNAs between CRC tissues and adjacent normal tissues were identified based on TCGA dataset, and the m6A-related miRNAs were screened. The CRC patients from TCGA were randomized (1:1) into training set and validation set, and the risk score was established in the training set. Next, risk score was verified in the validation set and GSE92928 from GEO datasets. Besides, the relationship among tumor mutational burden, immune microenvironment and risk score were analyzed. What's more, RT-qPCR were used to explore the expression levels of the miRNAs in risk score between SW480 and SW620. A total of 29 m6A-related miRNAs were screened out, and a 5-differentially expressed miRNAs risk score was established. Kaplan-Meier analysis and ROC curves revealed the risk score could predict the prognosis of CRC, accurately. Similarly, the patients in the high-risk group had shorter overall survival in GSE92928. The risk score was relevant with the tumor mutational burden and immune infiltration, and the expression of HAVCR2 was significant difference between 2 risk groups. The expression levels of miR-328-3p, miR-3934-5p, miR-664b-5p and miR-3677-3p were down-regulated in SW620 compared with SW480, only the expression level of miR-200c-5p was up-regulated in SW620. The findings provided the new insights into the correlation between miRNAs and m6A regulators. The m6A-related miRNAs could predict the prognosis of CRC and provide the valuable information of immunotherapy in CRC patients.

A novel intronic circular RNA circFGFR1int2 up-regulates FGFR1 by recruiting transcriptional activators P65/FUS and suppressing miR-4687-5p to promote prostate cancer progression.

Fibroblast growth factor receptor 1 (FGFR1) is a core component of the FGFs/FGFR pathway that activates multiple signalling pathways, including ERK1/2, PI3K/AKT, PLCγ, and NF-κB. Aberrant expression of FGFR1 due to gene amplification, chromosome rearrangement, point mutation, and epigenetic deregulations, have been reported in various cancers. FGFR1 overexpression has also been reported in prostate cancer (PCa), but the underlining mechanisms are not clear. Here we report a novel circular RNA, circFGFR1int2, derived from intron 2 of FGFR1 gene, which is overexpressed in PCa and associated with tumor progression. Importantly, we show that circFGFR1int2 facilitates FGFR1 transcription by recruiting transcription activators P65/FUS and by interacting with FGFR1 promoter. Moreover, we show that circFGFR1int2 suppresses post-transcriptional inhibitory effects of miR-4687-5p on FGFR1 mRNA. These mechanisms synergistically promote PCa cell growth, migration, and invasion. Overexpression of circFGFR1int2 is significantly correlated with higher tumor grade, Gleason score, and PSA level, and is a significant unfavorable prognosticator for CRPC-free survival (CFS) (RR = 3.277, 95% confidence interval: 1.192-9.009; P = 0.021). These findings unravelled novel mechanisms controlling FGFR1 gene expression by intronic circRNA and its potential clinicopathological utility as a diagnostic or therapeutic target.