Tumor-treating fields dosimetry in glioblastoma: Insights into treatment planning, optimization, and dose-response relationships.

Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment. This paper outlines and evaluates the current standards and methodologies in the estimation of the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields dosimetry. The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment. The current evidence for a correlation between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array "edge effect," electrical duty cycle, and skull-remodeling surgery. Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.

Prognostic value of Controlling Nutritional Status score for postoperative complications and biochemical recurrence in prostate cancer patients undergoing laparoscopic radical prostatectomy.

Background: Controlling Nutritional Status (CONUT) score was used for screening the preoperative nutritional status. The correlation between the CONUT score and the prognosis of patients with prostate cancer (PCa) has yet to be elucidated. Herein, we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy. Materials and methods: Data of 244 patients were retrospectively evaluated. Perioperative variables and follow-up data were analyzed. The patients were categorized into 2 groups according to their preoperative CONUT scores. Postoperative complication and incontinence rates were also compared. The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival (BCRFS) between the 2 groups. Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS. Results: Patients were categorized into the low-CONUT group (CONUT score <3, n = 207) and high-CONUT group (CONUT score ≥3, n = 37). The high-CONUT group had a higher overall complication rate (40.5% vs.19.3%, p = 0.004), a higher major complication rate (10.8% vs. 3.9%, p = 0.013), and longer postoperative length of stay (8 days vs. 7 days, p = 0.017). More fever, urinary infection, abdominal infection, scrotal edema, rash, and hemorrhagic events (all p values < 0.05) were observed in the high-CONUT group. A higher rate of urinary incontinence was observed in the high-CONUT group at 1 (34.4% vs. 13.2%, p = 0.030) and 3 months (24.1% vs. 8.2%, p = 0.023) postoperatively. The high-CONUT group had shorter medium BCRFS (23.8 months vs. 54.6 months, p = 0.029), and a CONUT score ≥3 was an independent risk factor for a shorter BCRFS (hazards ratio, 1.842; p = 0.026). Conclusions: The CONUT score is a useful predictive tool for higher postoperative complication rates and shorter BCRFS in patients with PCa who undergo laparoscopic radical prostatectomy.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy.

Esophageal cancer (ESC) is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract. Although the exact pathogenesis of ESC has not been fully elucidated, excessive oxidative stress is an important characteristic that leads to the development of many cancers. Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs, which alters the growth and proliferation of ESCs and promotes their metastasis. Natural compounds, including alkaloids, terpenes, polyphenols, and xanthine compounds, can inhibit reactive oxygen species production in ESCs. These compounds reduce oxidative stress levels and subsequently inhibit the occurrence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10, superoxide dismutase, the NF-+ACY-kappa+ADs-B/MAPK pathway, and the mammalian Nrf2/ARE target pathway. Thus, targeting tumor oxidative stress has become a key focus in anti-ESC therapy. This review discusses the potential of Natural products (NPs) for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment. The findings of this review provide a reference for drug development targeting ESCs. Nonetheless, further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Cancer-associated fibroblast exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment.

Metastasis is the main cause of deaths in prostate cancer (PCa). However, the exact mechanisms underlying PCa metastasis are not fully understood. In this study, we discovered pronounced hypoxia in primary lesions of metastatic PCa(mPCa). The exosomes secreted by cancer-associated fibroblasts (CAFs) under hypoxic conditions significantly enhance PCa metastasis both in vitro and in vivo. Through miRNA sequencing and reverse transcription quantitative PCR (RT-qPCR), we found that hypoxia elevated miR-500a-3p levels in CAFs exosomes. Subsequent RT-qPCR, western blotting, and dual luciferase reporter assays identified F-box and WD repeat domain-containing 7(FBXW7) as a target of miR-500a-3p. In addition, immunohistochemistry revealed that FBXW7 expression decreased with the progression of PCa, while heat shock transcription factor 1(HSF1) expression increased. Introducing an FBXW7 plasmid into PCa cells reduced their metastatic potential and significantly lowered HSF1 expression. These findings suggest that CAFs exosomes drive PCa metastasis via the miR-500a-3p/FBXW7/HSF1 axis in a hypoxic microenvironment. Targeting either hypoxia or exosomal miR-500a-3p could be a promising strategy for PCa management.

Flow-diverter stents in intracranial aneurysm treatment: impact on covered cerebral artery branches.

OBJECTIVE: Flow diverter stents (FDSs) have attracted interest for intracranial aneurysm (IA) treatment; however, occlusion of side branches and related complications have been reported. This study aimed to investigate the effects of FDSs in IA management when different branches of intracranial arteries are covered. MATERIALS AND METHODS: A cross-sectional study was conducted using PUBMED, Embase, Web of Science, and Cochrane databases to include randomized or nonrandomized comparative-designed studies from January 2000 to August 2022 which reported outcomes of occlusion/narrowing of branches after IA treatment using FDSs. The PRISMA guidelines were used for our report. A random-effects meta-analysis was conducted to pool the outcomes, which included incidence rates of occlusion/narrowing of FDS-covered branches, branch occlusion-related symptoms, obliteration of IAs, and ideal clinical outcomes (modified Rankin Scale score ≤2). RESULTS: The authors identified 57 studies involving 3789 patients with IA managed by FDSs covering different branches. During the median imaging follow-up at 12 months, the IA obliteration rate was satisfactory (>70%) when covering the ophthalmic artery (OA), posterior communicating artery (PComA), anterior choroidal artery (AChoA) or anterior cerebral artery (ACA), but not the middle cerebral artery-M2 segment (MCA-M2; 69.5%; 95% CI: 60.8-77.5%) and posterior inferior cerebellar artery (PICA; 59.1%, 13/22). The overall ideal clinical outcome was observed in 97.4% of patients (95% CI: 95.5-98.9%). Higher rates of occlusion/narrowing of branches were identified when FDSs covered the ACA (66.6%; 95% CI: 45.1-85.3%), PComA (44.3%; 95% CI: 34.2-54.6%), or MCA-M2 (39.2%; 95% CI: 24.5-54.7%); the risks were lower when covering the OA (11.8%; 95% CI: 8.8-15.1%), PICA (6.8%; 95% CI: 1.5-14.5%), and AchoA (0.5%; 95% CI: 0.0-2.9%). The risk of branch occlusion-related complications was low (incidence rate <5%) for each of the six evaluated branches. CONCLUSIONS: Acceptable outcomes were identified following treatment of IAs when FDSs were placed across each of the six studied cerebral arteries. Treatment decisions regarding FDS placement across branch arteries should be made with the risk of complications from branch occlusion in mind.

Overexpression of PPM1B inhibited chemoresistance to temozolomide and proliferation in glioma cells.

Protein phosphatase magnesium-dependent 1B (PPM1B) functions as IKKß phosphatases to terminate nuclear factor kappa B (NF-κB) signaling. NF-κB signaling was constitutively activated in glioma cells. At present, little is known about the role of PPM1B in glioma. In the current study, we found that the expression of PPM1B was reduced in glioma tissues and cells, and decreased expression of PPM1B was related to poor overall survival of patients. Overexpression of PPM1B inhibited the proliferation and promoted apoptosis of glioma cells. Moreover, PPM1B overexpression reduced the phosphorylation of IKKß and inhibited the nuclear localization of NF-κBp65. PDTC, an inhibitor of NF-κB signaling, reversed PPM1B-knockdown-induced cell proliferation. Furthermore, overexpression of PPM1B enhanced the sensitivity of glioma cells to temozolomide. In vivo experiments showed that overexpression of PPM1B could inhibit tumor growth, improve the survival rate of nude mice, and enhance the sensitivity to temozolomide. In conclusion, PPM1B suppressed glioma cell proliferation and the IKKß-NF-κB signaling pathway, and enhanced temozolomide sensitivity of glioma cells.

N6-methyladenosine-mediated overexpression of long noncoding RNA ADAMTS9-AS2 triggers neuroblastoma differentiation via regulating LIN28B/let-7/MYCN signaling.

Neuroblastomas have shed light on the differentiation disorder that is associated with spontaneous regression or differentiation in the same tumor at the same time. Long noncoding RNAs (lncRNAs) actively participate in a broad spectrum of biological processes. However, the detailed molecular mechanisms underlying lncRNA regulation of differentiation in neuroblastomas remain largely unknown. Here, we sequenced clinical samples of ganglioneuroma, ganglioneuroblastoma, and neuroblastoma. We compared transcription profiles of neuroblastoma cells, ganglion cells, and intermediate state cells; verified the profiles in a retinoic acid-induced cell differentiation model and clinical samples; and screened out the lncRNA ADAMTS9 antisense RNA 2 (ADAMTS9-AS2), which contributed to neuroblastoma differentiation. ADAMTS9-AS2 upregulation in neuroblastoma cell lines inhibited proliferation and metastatic potential. Additional mechanistic studies illustrated that the interactions between ADAMTS9-AS2 and LIN28B inhibited the association between LIN28B and primary let-7 (pri-let-7) miRNA, then released pri-let-7 into cytoplasm to form mature let-7, resulting in the inhibition of oncogene MYCN activity that subsequently affected cancer stemness and differentiation. Furthermore, we showed that the observed differential expression of ADAMTS9-AS2 in neuroblastoma cells was due to N6-methyladenosine methylation. Finally, ADAMTS9-AS2 upregulation inhibited proliferation and cancer stem-like capabilities in vivo. Taken together, these results show that ADAMTS9-AS2 loss leads to malignant neuroblastoma by increasing metastasis and causing dysfunctional differentiation.

Afzelin induces immunogenic cell death against lung cancer by targeting NQO2.

BACKGROUND: Lung cancer is one of the most common malignant cancers worldwide. Previous studies have shown that Afzelin, a flavonoid, possesses anticancer activity. The aim of this study was to explore Afzelin's effect on lung cancer cells and delineate potential anti-cancer mechanism. METHODS: The effect of Afzelin on cell viability, proliferation, and apoptosis of lung cancer cells i.e., A549 and H1299 cells, was studied. The targets for Afzelin in lung cancer were predicted using SwissTargetPrediction, Next, the GO analysis and pathway enrichment were analyzed using String. For in vitro studies, the overexpression plasmid of NQO2, the identified target of Afzelin, was transfected into Afzelin-treated cells to verify the regulatory role of Afzelin on its target and signaling pathway. RESULTS: In in vitro studies, Afzelin markedly inhibited cell viability, proliferation, and raised apoptotic rate of A549 and H1299 cells. In addition, Afzelin activated endoplasmic reticulum (ER) stress and increased ATP, HMGB1, and CRT levels in lung cancer cells, indicating that Afzelin induced immunogenic cell death (ICD). SwissTargetPrediction identified NQO2 as a target of Afzelin. Further, Afzelin markedly inhibited NQO2 protein expression and in turn, overexpression of NQO2 attenuated the effect of Afzelin on A549 and H1299 cells. CONCLUSION: Afzelin inhibits lung cancer progression by targeting NQO2, in turn, activating ER stress and inducing ICD.

Disease burden based on gender and age and risk factors for stroke in China, 2019. / 2019å¹´ä¸­å›½è„‘å’ä¸­æ€§åˆ«å’Œå¹´é¾„åˆ«ç–¾ç— è´Ÿæ‹ åŠå ¶å±é™©å› ç´ .

OBJECTIVES: Stroke has become the leading cause of death and disability among adults in China. This study aims to analyze the disease burden based on gender and age and the risk factors for stroke subtypes in China 2019, and to provide reference for targeted stroke prevention and control. METHODS: Based on 2019 data of the Global Burden of Disease (GBD), the gender and age in patients with different stroke subtypes (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage) in China 2019 was described by using disability-adjusted life years (DALY), and attributable burden of related risk factors was analyzed. RESULTS: In 2019, the burden of intracranial hemorrhage was the heaviest one in China, resulting in 22.210 6 million person years of DALY, following by ischemic stroke and subarachnoid hemorrhage, resulting in 21.393 9 and 2.344 7 million person years of DALY, respectively. Among them, except the 0-14 age group, the disease burden of different subtypes of stroke in men was higher than that in women. The disease burden of ischemic stroke was increased with age in both men and women, with the heaviest disease burden in ≥70 years group. The disease burden of intracranial hemorrhage and subarachnoid hemorrhage was the heaviest in males aged 50-69 years old, and in females aged ≥70 years and 50-69 years, respectively. Metabolic factors were the main risk factors in all ages of different stroke subtypes, and the most important risk factor was high systolic blood pressure. Other risk factors were different between men and women. Smoking, high body mass index, high low-density lipoprotein, and outdoor particulate matter pollution were the main risk factors for stroke in men, while high body mass index, outdoor particulate matter pollution, and high fasting blood glucose were the main risk factors of stroke in women. The main risk were different among different age groups. CONCLUSIONS: The burden and attributable risk factors for different stroke subtypes are discrepancy in different gender and age groups. Targeted interventions should be conducted in the future to reduce the burden of stroke.

Berberine: An inspiring resource for the treatment of colorectal diseases.

Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.

Temozolomide and chloroquine co-loaded mesoporous silica nanoparticles are effective against glioma.

The past decades have witnessed great progress in nanoparticle-based cancer-targeting drug delivery systems, but their therapeutic potentials is yet to be fully exploited. In this research, temozolomide (TMZ) and chloroquine (CQ) were loaded into the mesoporous silica nanoparticles (MSNs), the surface was coated with polydopamine (PDA), and the complex was coupled with arginine-glycine-aspartic (RGD) to successfully prepare TMZ/CQ@MSN-RGD. RGD-MSNs accumulated more in the cell and tumor models than in unmodified MSNs in the in vitro and in vivo experiments and can directly induce apoptosis and autophagy in tumor cells. In addition, TMZ/CQ@MSN-RGD therapy enhanced the apoptosis effect of the RGD-MSNs in glioma. Therefore, the combination of autophagy inhibitor with chemotherapy drugs in nanocarriers may promote therapeutic efficacy in treating glioma.

Individual trigger factors for hemorrhagic stroke: Evidence from case-crossover and self-controlled case series studies.

BACKGROUND: Hemorrhagic stroke (HS) is a sudden-onset disease with high mortality and disability rates, and it is crucial to explore the triggers of HS. In this study, we analyzed individual triggers for HS to provide a basis for HS prevention and intervention. METHODS: A systematic search of five databases was conducted until December 2022. Studies on HS-related individual triggers conducted using a case-crossover study or self-controlled case series design were included in the descriptive summary and comprehensive evidence synthesis of each trigger. RESULTS: A total of 39 studies were included after the screening, and 32 trigger factor categories were explored for associations. Potential trigger factors for HS were as follows: Antiplatelet (odd ratio (OR), 1.10; 95% confidence interval (CI), 1.00-1.21) and anticoagulant (OR, 5.43; 95% CI, 2.04-14.46) medications, mood stabilizers/antipsychotics (OR, 1.33; 95% CI, 1.07-1.65), infections (OR, 2.15; 95% CI, 1.73-2.67), vaccinations (relative risk, 1.11; 95% CI, 1.02-1.21), physical exertion (OR, 2.08; 95% CI, 1.58-2.74), cola consumption (OR, 5.45; 95% CI, 2.76-10.76), sexual activity (OR, 7.49; 95% CI, 2.23-25.22), nose blowing (OR range, 2.40-56.40), defecation (OR, 16.94; 95% CI, 3.40-84.37), and anger (OR, 3.59; 95% CI, 1.56-8.26). No associations were observed with illicit drug use (OR, 2.05; 95% CI, 0.52-8.06) or cigarette smoking (OR, 0.81; 95% CI, 0.52-1.24) and HS. CONCLUSIONS: Individual triggers, including several medications, infections, vaccinations, and behaviors, may trigger HS onset. Direct control measures for behavioral triggers can play a crucial role in preventing HS. High-risk populations should receive personalized therapies and monitoring measures during the medication treatment to balance the risk of acute HS and the basic diseases.

Clinicopathological characteristics, risk factors and prognostic value of intrarenal vascular lesions in IgA nephropathy.

BACKGROUND: The aim was to study clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with vascular lesions. METHODS: We enrolled a Chinese cohort with 458 biopsy-confirmed primary IgAN patients for a retrospective analysis. They were divided into three groups according to vascular lesions: no vascular lesions (n = 239), arterio-/arteriolosclerosis (n = 181) and microangiopathic lesions (n = 38). The clinicopathological features and renal outcome were recorded. In univariate and multivariate models, association between vascular lesions and renal outcome and vascular lesions associated clinical factors were analyzed. RESULTS: Patients with vascular lesions presented worse clinical characteristics with regard to blood pressure and kidney function, and segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2) and lymphocytes and monocytes infiltration were more common. Furthermore, older age, hyperuricemia, proteinuria, global glomerulosclerosis and endocapillary hypercellularity (E1) were more severe in patients with simple arterio-/arteriolosclerosis. By multivariate logistic regression, age, MAP and eGFR were significantly associated with vascular lesions. Vascular lesions, especially arterio-/arteriolosclerosis, were significantly associated with poorer renal survival in IgAN patients, and renal survival was similar whether patients with arterio-/arteriolosclerosis received immunosuppressive therapy. In addition to eGFR, arterio-/arteriolosclerosis, along with arterial intimal fibrosis, was an independent predictor for renal survival in multivariate Cox analyses. CONCLUSION: IgAN patients with vascular lesions, especially with arterio-/arteriolosclerosis, presented more severe clinicopathological features. Renal function, blood pressure and age contributed to distinguishing patients with vascular lesions. Arterio-/arteriolosclerosis lesions were associated with poorer renal survival.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis.

Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies. Metastasis is a complicated multistep process, which is determined by complex genetic alterations. Despite the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging. Here, we established a high-throughput and piggyBac transposon-based genetic screening platform, which enables either reduced or increased expression of chromosomal genes near the incorporation site of the gene search vector cassette that contains a doxycycline-regulated promoter. Using this strategy, we identified YWHAZ as a key regulator of pancreatic cancer metastasis. We demonstrated that functional activation of Ywhaz by the gene search vector led to enhanced metastatic capability in mouse pancreatic cancer cells. The metastasis-promoting role of YWHAZ was further validated in human pancreatic cancer cells. Overexpression of YWHAZ resulted in more aggressive metastatic phenotypes in vitro and a shorter survival rate in vivo by modulating epithelial-to-mesenchymal transition. Hence, our study established a high-throughput screening method to investigate the functional relevance of novel genes and validated YWHAZ as a key regulator of pancreatic cancer metastasis.

Granuloma formation after repeated episodes of peritoneal dialysis catheter-related infection, a case report.

BACKGROUND: Peritoneal catheter related infection is one of the main complications and the major cause of technical failure of peritoneal dialysis (PD) treatment. However, PD catheter tunnel infection can be difficult to diagnosis and resolve. We presented a rare case in which a granuloma formation after repeated episodes of peritoneal dialysis catheter-related infection. CASE PRESENTATION: A 53-year-old female patient with kidney failure due to chronic glomerulonephritis treated with peritoneal dialysis for 7 years. The patient had repeated exit-site and tunnel inflammation, and repeated suboptimal courses of antibiotics. She switched to hemodialysis after 6 years in a local hospital without the peritoneal dialysis catheter being removed. The patient complained of an abdominal wall mass that lasted for several months. She was admitted to the Department of surgery to undergo mass resection. The resected tissue of the abdominal wall mass was sent for pathological examination. The result showed foreign body granuloma with necrosis and abscess formation. After the surgery, the infection did not recur. CONCLUSIONS: The following key points can be learned from this case: 1. It is important to strengthen patient follow-up. 2.The PD catheter should be removed as early as possible in patients who do not need long-term PD, especially in patients with a history of exit-site and tunnel infections. 3. For patients presenting abnormal subcutaneous mass, attention should be paid to the possibility of the granuloma formation of infected Dacron cuffs of the PD catheter. If catheter infection occurs repeatedly, catheter removal and debridement should be considered.

Identification of the lncRNA-miRNA‒mRNA regulatory network for middle cerebral artery occlusion-induced ischemic stroke.

Stroke known as a neurological disease has significant rates of disability and mortality. Middle cerebral artery occlusion (MCAO) models in rodents is crucial in stroke research to mimic human stroke. Building the mRNA and non-conding RNA network is essential for preventing MCAO-induced ischemic stroke occurrence. Herein, genome-wide mRNA, miRNA, and lncRNA expression profiles among the MCAO group at 3 h, 6 h, and 12 h after surgery and controls using high-throughput RNA sequencing. We detected differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between the MCAO and control groups. In addition, biological functional analyses were conducted, including GO/KEGG enrichment analysis, and protein-protein interaction analysis (PPI). GO analysis indicated that the DE-mRNAs were mainly enriched in several important biological processes as lipopolysaccharide, inflammatory response, and response to biotic stimulus. The PPI network analysis revealed that the 12 DE-mRNA target proteins showed more than 30° with other proteins, and the top three proteins with the highest node degree were Alb, IL-6, and TNF. In the DE-mRNAs, we found the mRNA of Gp6 and Elane interacting with two miRNAs (novel_miR_879 and novel_miR_528) and two lncRNAs (MSTRG.348134.3 and MSTRG.258402.19). As a result of this study, a new perspective can be gained into the molecular pathophysiology leading to the formation of MCAO. The mRNA-miRNA‒lncRNA regulatory networks play an important role in MCAO-induced ischemic stroke pathogenesis and could be applied to the treatment and prevention of ischemic stroke in the future.

A Deep Learning-Based System Trained for Gastrointestinal Stromal Tumor Screening Can Identify Multiple Types of Soft Tissue Tumors.

The accuracy and timeliness of the pathologic diagnosis of soft tissue tumors (STTs) critically affect treatment decision and patient prognosis. Thus, it is crucial to make a preliminary judgement on whether the tumor is benign or malignant with hematoxylin and eosin-stained images. A deep learning-based system, Soft Tissue Tumor Box (STT-BOX), is presented herein, with only hematoxylin and eosin images for malignant STT identification from benign STTs with histopathologic similarity. STT-BOX assumed gastrointestinal stromal tumor as a baseline for malignant STT evaluation, and distinguished gastrointestinal stromal tumor from leiomyoma and schwannoma with 100% area under the curve in patients from three hospitals, which achieved higher accuracy than the interpretation of experienced pathologists. Particularly, this system performed well on six common types of malignant STTs from The Cancer Genome Atlas data set, accurately highlighting the malignant mass lesion. STT-BOX was able to distinguish ovarian malignant sex-cord stromal tumors without any fine-tuning. This study included mesenchymal tumors that originated from the digestive system, bone and soft tissues, and reproductive system, where the high accuracy of migration verification may reveal the morphologic similarity of the nine types of malignant tumors. Further evaluation in a pan-STT setting would be potential and prospective, obviating the overuse of immunohistochemistry and molecular tests, and providing a practical basis for clinical treatment selection in a timely manner.

MRI-measured periprostatic adipose tissue volume as a prognostic predictor in prostate cancer patients undergoing laparoscopic radical prostatectomy.

In this study, we evaluated the association between the PPAT volume and the prognosis of PCa patients after LRP. We retrospectively analysed data of 189 PCa patients who underwent LRP in Beijing Chaoyang Hospital. Volumes of PPAT and prostate were measured by magnetic resonance imaging (MRI), and normalized PPAT volume was computed (PPAT volume divided by prostate volume). Patients were then stratified into the high-PPAT group (n = 95) and low-PPAT group (n = 94) by the median of normalized PPAT volume (73%). The high-PPAT group had significantly higher Gleason score (total score 8 or more, 39.0% vs. 4.3%, p < 0.001) and pathological stage (stage T3b, 28.4% vs. 13.8%, p = 0.048). No significant correlation between normalized PPAT volume and body mass index (ρ = -0.012, p = 0.872) was observed. Kaplan-Meier curve analysis showed the high-PPAT group had significantly shorter biochemical recurrence (BCR) interval (median progression-free survival time 15.9 months vs. 32.7 months, p = 0.001). Univiarate and multivariate Cox regression analyses showed high normalized PPAT volume (>73%) (hazard ratio 1.787 [1.075-3.156], p = 0.002) were independent risk factors for BCR post-operatively. In conclusion, MRI-measured PPAT volume is of significant prognostic value for PCa patients undergoing LRP.