Analysis of 3D pathology samples using weakly supervised AI.

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.

A hybrid open-top light-sheet microscope for versatile multi-scale imaging of cleared tissues.

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a flexible system that can address imaging applications with varied requirements in terms of resolution, sample size, tissue-clearing protocol, and transparent sample-holder material. Here, we present a 'hybrid' system that combines a unique non-orthogonal dual-objective and conventional (orthogonal) open-top light-sheet (OTLS) architecture for versatile multi-scale volumetric imaging. We demonstrate efficient screening and targeted sub-micrometer imaging of sparse axons within an intact, cleared mouse brain. The same system enables high-throughput automated imaging of multiple specimens, as spotlighted by a quantitative multi-scale analysis of brain metastases. Compared with existing academic and commercial light-sheet microscopy systems, our hybrid OTLS system provides a unique combination of versatility and performance necessary to satisfy the diverse requirements of a growing number of cleared-tissue imaging applications.

A peptide alleviated oxidative damages in the L02 cells and mice liver.

The liver is vitally metabolic for a multitude of biochemical reactions. Consequently, it generates many free radicals and reactive oxygen species, rendering it more susceptible to oxidative stress-induced damage. Oxidative stress represents a pivotal factor in the pathogenesis of liver diseases. We screened some antioxidant peptides previously. Here we investigated whether the peptides could attenuate oxidative damage with APPH in L02 cells. The results showed that one of the peptides, sequence FETLMPLWGNK, could decrease the excessive reactive oxygen species, increase antioxidant enzyme activity and protect mitochondrial function, reduce the ratio of apoptosis and S phase cycle arrest, and improve the survival rate of L02 cells damaged by APPH compared to cells of the control group. Then the peptide was evaluated in mice that CCl4 injured. We found that CCl4-injured mice had significantly increased serum inflammatory factors and liver injury markers, a large number of inflammatory cell infiltration, and local necrosis in the liver. The peptide could reduce inflammation, and improve liver pathological changes. This phenomenon may be associated with the activation of the Nrf2 signaling pathway. Concurrently, the peptide protects the liver by regulating the expression of proteins related to the mitochondrial apoptosis pathway (p53, Bax, Bcl-2, and Caspase3) and mitophagy-related proteins (PINK1, Parkin, and AMPKα). Therefore, the results indicated that the peptide is an active substance with antioxidant activity and anti-inflammatory effects.

High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model.

PURPOSE: The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months. METHODS: Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored. RESULT: The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months. CONCLUSION: The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears. LEVEL OF EVIDENCE: NA.

Artificial Intelligence-Triaged 3-Dimensional Pathology to Improve Detection of Esophageal Neoplasia While Reducing Pathologist Workloads.

Early detection of esophageal neoplasia via evaluation of endoscopic surveillance biopsies is the key to maximizing survival for patients with Barrett's esophagus, but it is hampered by the sampling limitations of conventional slide-based histopathology. Comprehensive evaluation of whole biopsies with 3-dimensional (3D) pathology may improve early detection of malignancies, but large 3D pathology data sets are tedious for pathologists to analyze. Here, we present a deep learning-based method to automatically identify the most critical 2-dimensional (2D) image sections within 3D pathology data sets for pathologists to review. Our method first generates a 3D heatmap of neoplastic risk for each biopsy, then classifies all 2D image sections within the 3D data set in order of neoplastic risk. In a clinical validation study, we diagnose esophageal biopsies with artificial intelligence-triaged 3D pathology (3 images per biopsy) vs standard slide-based histopathology (16 images per biopsy) and show that our method improves detection sensitivity while reducing pathologist workloads.

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). METHODS: SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan-Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). RESULTS: The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. CONCLUSIONS: Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.

Gestational age-specific reference standards of low-lying conus medullaris level in fetuses: a prospective cohort study.

PURPOSE: To explore the position change of fetal conus medullaris by ultrasound, and to propose gestational age-specific references for the lower limits of fetal conus medullaris level. METHODS: We prospectively collected the imaging and clinical data of fetuses whose mothers accepted routine prenatal ultrasonic follow-ups in the Department of Medical Ultrasonics, Chinese PLA General Hospital, between November 2020 and April 2021. By assigning to the conus medullaris levels, calculating statistical data, and performing linear regression analysis, we determined the correlation between the conus medullaris level and gestational week, as well as between the 95th percentile of the conus medullaris level, i.e., the lower limit of the conus medullaris level, and gestational week. RESULTS: We included 1202 different fetuses at 17-40 gestational weeks in the study. Both the conus medullaris level and the 95th percentile of the conus medullaris level were linearly correlated with gestational week. We calculated the adjusted values of the lower limits of fetal conus medullaris levels, that is, the theoretical references of the lower limits, according to the linear regression equation, and composed a comparison table. CONCLUSION: The fetal conus medullaris position continues changing cranially with gestational weeks during the whole pregnancy. The conus medullaris of a term fetus should not lie below the L2 vertebra level at birth. We proposed reference criteria of fetal low-lying conus medullaris for each gestational week from 17 to 40 weeks of gestational age, which potentially help prompt diagnosis and improve prognosis of fetal tethered cord syndrome.

Conus medullaris migration during the third trimester: A retrospective study.

OBJECTIVE: To explore the migration process of the conus medullaris (CM) and propose a normal range of CM levels during the third trimester. METHOD: We retrospectively collected the ultrasonographic and clinical data of 588 fetuses during the third trimester. We located the CM and assigned scores. One-way analysis of variance and linear regression analyses were used to statistically analyze CM migration. Statistical significance was set at p < 0.05. RESULTS: The CM levels were statistically different among the different gestational weeks of the third trimester. The CM level showed a linear regression correlation with the gestational weeks. On an average, the CM migrated from the top third of the L2 vertebra to the L1/2 intervertebral disc level. CONCLUSION: The CM continues to migrate, from the top third of the L2 vertebra to the L1/2 intervertebral disc level, during the third trimester. The term infant could have the CM at the normal adult level at birth. At the beginning of the third trimester, a CM located above the L2/3 intervertebral disc level could be normal; the CM location at the L3 vertebra level could be physiological and needs follow-up; and a CM presenting below the L3 vertebra level might indicate tethered cord syndrome. The fetus with a CM significantly above the L1/2 intervertebral disc level may have caudal regression syndrome.

High Prevalence of Vitamin D Deficiency in Pregnant Women in South China.

Objective: To investigate the vitamin D status of pregnant women in the Liuzhou area and assess the effects of maternal vitamin D status on the cord blood of their newborns. Subjects and methods: This study included 8852 pregnant women and 2000 newborns. The serum 25-hydroxyvitamin D [25(OH)D] levels of the 8852 pregnant women and the cord blood of 2000 newborns were measured. Results: The results showed that the average level of 25(OH)D in pregnant women in this area was 76.55 nmol/L, and women in different trimesters had different vitamin D levels (p < 0.001). The overall prevalence of vitamin D deficiency (<75 nmol/L) in pregnant women was 62.34%, and the proportion of severe deficiency (<25 nmol/L) was 0.25%. Vitamin D deficiency was more prevalent in the winter and spring than in the summer and autumn (p < 0.001). Pregnant women who had regular vitamin D supplementation had higher levels of 25(OH)D than the women with discontinuous supplementation or no supplementation (p < 0.001). Conclusions: Vitamin D deficiency was prevalent in pregnant women in the Liuzhou area. There were differences in vitamin D levels between the three trimesters and different seasons. For pregnant women with vitamin D deficiency, it is important to scientifically determine the appropriate level of vitamin D supplementation to ensure the health of mothers and babies.

miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. However, little is known on the biological and functional significance of miR-133b/FGFR1 regulation in osteosarcoma. METHODS: The expressions of miR-133b and FGFR1 were examined by RT-qPCR and compared between 30 paired normal bone tissues and OS tissues, and also between normal osteoblasts and three OS cells lines, MG-63, U2OS, and SAOS-2. Using U2OS and MG-63 as the model system, the functional significance of miR-133b and FGFR1 was assessed on cell viability, proliferation, apoptosis, migration/invasion, and epithelial-mesenchymal transition (EMT) by overexpressing miR-133b and down-regulating FGFR1 expression, respectively. Furthermore, the signaling cascades controlled by miR-133b/FGFR1 were examined. RESULTS: miR-133b was significantly down-regulated while FGFR1 robustly up-regulated in OS tissues and OS cell lines, when compared to normal bone tissues and normal osteoblasts, respectively. Low miR-133b expression and high FGFR1 expression were associated with location of the malignant lesion, advanced clinical stage, and distant metastasis. FGFR1 was a direct target of miR-133b. Overexpressing miRNA-133b or knocking down FGFR1 significantly reduced the viability, proliferation, migration/invasion, and EMT, but promoted apoptosis of both MG-63 and U2OS cells. Both the Ras/MAPK and PI3K/Akt intracellular signaling cascades were inhibited in response to overexpressing miRNA-133b or knocking down FGFR1 in OS cells. CONCLUSION: miR-133b, by targeting FGFR1, presents a plethora of tumor suppressor activities in OS cells. Boosting miR-133b expression or reducing FGFR1 expression may benefit OS therapy.

Interference effect from noise on range-gated laser ranging and tracking system.

Influence of high-repetition-rate noise on a range-gated laser ranging and tracking system (LRTS) is studied both theoretically and experimentally. The interference mechanism of high-repetition-rate noise on range gates is revealed. The interference effect, especially the effect caused by relative shift between signal and noise, is presented through theoretical analysis and numerical simulation. In order to verify the simulation model, both electrical closed circuit and optical circuit experiments are further conducted. Both the simulation model and experiment results show that both periodic and nonperiodic noise pulses can enter the range gates of a LRTS and affect its operation with both their high repetition rate and relative shift to echo pulses.

Single laser free-space duplex communication system with adaptive threshold technique and BER analysis in weak turbulent atmosphere.

A free space duplex communication system with a single laser and a modulated retro-reflector is presented. A method to minimize the echo wave bit error rate (BER) of this system is proposed by setting the optimum threshold automatically based on the measured mean power and irradiance variances with log-normal distribution and the Bayes minimum classification error criterion. Experiments were taken at a distance of 1.55 km in a weak turbulence and the measured BER was 0.0213. The BER performance of this system is studied and the result shows the experimental BER is in good accordance with the theoretical value.

The relationship between polymorphism of IGF2BP2 gene rs4402960 and risk of pan-cancer: a meta-analysis and a bioinformatics analysis.

OBJECTIVE: To conduct a meta-analysis and a bioinformatics analysis to assess the relationship between IGF2BP2 gene polymorphism and pan-cancer risk. METHODS: PubMed, EMBASE, and Web of Science were conducted to literature searches. The heterogeneity test was used in five genetic models. Odds ratios (OR), 95% confidence intervals (CI), and p-values were used to evaluate the combined effects of various genetic models. Subgroup analysis and Meta-regression analysis were used to analyze the characteristics of heterogeneity. Sensitivity analysis and publication bias were also performed. Transcriptomic information on IGF2BP2 was downloaded and analyzed from the TCGA and GTEx databases. GEPIA (http://gepia.cancer-pku.cn/) was performed to analyze the relationship between IGF2BP2 expression and cancer tissue. RESULTS: This meta-analysis contained 7 case-control studies, with 5,908 cases and 7,890 controls. There were significant differences in the heterozygous genetic model of IGF2BP2 gene rs4402960 polymorphism (OR = 1.080, 95% CI = 1.003-1.163, p = 0.041). In subgroup analysis based on ethnicity, There was a statistical significant association in Chinese (heterozygous: OR = 1.110, 95% CI = 1.010-1.220, p = 0.030). Bioinformatics analysis found that IGF2BP2 was over-expressed in pan-cancer (p < 0.01). In addition, the Kaplan-Meier estimate showed that there is statistical significance of OS between the low and high IGF2BP2 TPM groups in Lung adenocarcinoma (p <0.001). CONCLUSIONS: To sum up, IGF2BP2 gene polymorphism may be related to cancer risk. IGF2BP2 has diagnostic value in the diagnosis and treatment of pan-cancer.

Unleashing the power of AI in detecting metal surface defects: an optimized YOLOv7-tiny model approach.

The detection of surface defects on metal products during the production process is crucial for ensuring high-quality products. These defects also lead to significant losses in the high-tech industry. To address the issues of slow detection speed and low accuracy in traditional metal surface defect detection, an improved algorithm based on the YOLOv7-tiny model is proposed. Firstly, to enhance the feature extraction and fusion capabilities of the model, the depth aware convolution module (DAC) is introduced to replace all ELAN-T modules in the network. Secondly, the AWFP-Add module is added after the Concat module in the network's Head section to strengthen the network's ability to adaptively distinguish the importance of different features. Finally, in order to expedite model convergence and alleviate the problem of imbalanced positive and negative samples in the study, a new loss function called Focal-SIoU is used to replace the original model's CIoU loss function. To validate the effectiveness of the proposed model, two industrial metal surface defect datasets, GC10-DET and NEU-DET, were employed in our experiments. Experimental results demonstrate that the improved algorithm achieved detection frame rates exceeding 100 fps on both datasets. Furthermore, the enhanced model achieved an mAP of 81% on the GC10-DET dataset and 80.1% on the NEU-DET dataset. Compared to the original YOLOv7-tiny algorithm, this represents an increase in mAP of nearly 11% and 9.2%, respectively. Moreover, when compared to other novel algorithms, our improved model demonstrated enhanced detection accuracy and significantly improved detection speed. These results collectively indicate that our proposed enhanced model effectively fulfills the industry's demand for rapid and efficient detection and recognition of metal surface defects.

Enhanced outcomes in residual or recurrent craniopharyngioma: evaluating combined gamma knife and phosphorus-32 brachytherapy.

BACKGROUND: Managing residual and recurrent craniopharyngioma effectively is crucial for improving patient outcomes. This study evaluates the combined use of gamma knife and phosphorus-32 brachytherapy, offering insights into alternative, less invasive treatment strategies. METHODS: We conducted a retrospective analysis of 97 patients treated from 2010 to 2016 for residual and recurrent craniopharyngioma using gamma knife and phosphorus-32 brachytherapy. We classified these patients into three groups: superficial solid (Group A), simple cystic (Group B), and mixed cystic-solid (Group C). We assessed the treatment's effectiveness by the tumor control rates and evaluated safety by monitoring vision, endocrine function improvements, and complication rates. RESULTS: The treatment achieved complete and adequate control rates of 49.5% and 87.6%, respectively. We observed improvements in vision or visual fields in 55.1% of the patients. The morbidity rate was 15.5%. The study found no significant differences in tumor control rates among the various lesion types. CONCLUSION: The combination of gamma knife and phosphorus-32 brachytherapy presents a viable, minimally invasive alternative for treating residual and recurrent craniopharyngioma. It offers high tumor control and functional improvement rates, suggesting its potential as a preferred strategy in some instances.

Nerve Cuff Reconstruction for Sacral Duct Tarlov Cyst.

OBJECTIVE: To investigate factors influencing the long-term prognosis of patients with sacral Tarlov syndrome after nerve root cuff reconstruction. METHODS: A total of 42 patients with sacral Tarlov cysts who underwent nerve root cuff reconstruction at the First Medical Center of the Chinese PLA General Hospital between December 2015 and December 2021 were retrospectively reviewed. All cases were confirmed using magnetic resonance imaging and pathology. All patients were followed up for 24 months after surgery. Improvement in self-evaluation of health was defined as a good prognosis, while a decline in self-evaluation of health was defined as a poor prognosis. The demographic characteristics and clinical data were compared between patients with good and poor prognoses. Multivariate logistic regression analysis was performed, taking poor prognosis as the dependent variable and parameters with P < 0.1 in the univariate analysis as independent variables to identify the risk factors. RESULTS: Significant differences were observed in disease duration, lower limb weakness, defecation dysfunction, and defecation dysfunction between patients with good and poor prognoses. Multivariate logistic regression analysis showed that disease duration (Odds ratio: 0.961, 95% confidence interval: 0927-0.995) and defecation dysfunction (Odds ratio: 0.005, 95% confidence interval: 0.0-0.368) were independent risk factors for poor prognosis after nerve cuff reconstruction in patients with sacral Tarlov cysts (all P < 0.05). CONCLUSIONS: Patients with sacral Tarlov cysts undergoing nerve root cuff reconstruction, particularly those with longer preoperative disease duration and dysuria, are at increased risk of poor long-term prognosis.

Skull-femoral traction followed by osteotomy correction is a safe and effective treatment for severe scoliosis with split cord malformation.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of skull-femoral traction followed by osteotomy correction in patients with severe spinal scoliosis and split cord malformation. METHODS: We retrospectively analyzed ten cases of severe spinal scoliosis with Pang I type split cord malformation treated between August 2012 and August 2023. Patients underwent skull-femoral traction prior to osteotomy correction. We assessed changes in height, weight, coronal and sagittal Cobb's angles, and physiological indicators such as vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and blood gas levels before, during, and after treatment. RESULTS: Traction duration ranged from 9 to 19 days, with height and weight showing significant increases post-treatment. The coronal Cobb's angle improved from pre-treatment to post-corrective surgery and remained stable at the final follow-up. Similar improvements were observed in the sagittal plane. Physiological indicators such as VC, FVC, and FEV1, as well as blood gas levels, normalized after treatment. Nutritional status, indicated by triceps skinfold thickness, albumin, and transferrin concentrations, also improved. No neurological complications or device-related complications occurred during or after treatment. CONCLUSION: Skull-femoral traction followed by osteotomy correction is a safe and effective treatment for severe spinal scoliosis with split cord malformation, offering an alternative to high-risk procedures.

Validation of CDC45 as a novel biomarker for diagnosis and prognosis of gastric cancer.

Background: Cell division cycle protein 45 (CDC45) has been demonstrated to play vital roles in the progression of various malignancies. However, the clinical significance of CDC45 in gastric cancer (GC) remains unreported. Method: In this study, we employed the TCGA database and the TCGA & GTEx dataset to compare the mRNA expression levels of CDC45 between gastric cancer tissues and adjacent or normal tissues (p < 0.05 was considered statistically significant), which was further validated in multiple datasets including GSE13911, GSE29272, GSE118916, GSE66229, as well as RT-qPCR. Furthermore, we harnessed the Human Protein Atlas (HPA) to evaluate the protein expression of CDC45, which was subsequently verified through immunohistochemistry (IHC). To ascertain the diagnostic utility of CDC45, receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were calculated in TCGA database, and further validated it in TCGA & GTEx and GSE66229 datasets. The Kaplan-Meier method was used to reveal the prognostic importance of CDC45 in The Cancer Genome Atlas (TCGA) database and authenticated through the GSE66229, GSE84433, and GSE84437 datasets. Through cBioPortal, we identified co-expressed genes of CDC45, and pursued enrichment analysis. Additionally, we availed gene set enrichment analysis (GSEA) to annotate the biological functions of CDC45. Results: Differential expression analysis revealed that CDC45 was significantly upregulated at both the mRNA and protein levels in GC (all p < 0.05). Remarkably, CDC45 emerged as a promising prognostic indicator and a novel diagnostic biomarker for GC. In a comprehensive the drug susceptibility analysis, we found that patients with high expression of CDC45 had high sensitivity to various chemotherapeutic agents, among which 5-fluorouracil, docetaxel, cisplatin, and elesclomol were most evident. Furthermore, our findings suggested a plausible association between CDC45 and immune cell infiltration. Enrichment analysis revealed that CDC45 and its associated genes may play crucial roles in muscle biofunction, whereas GSEA demonstrated significant enrichment of gene sets pertaining to G protein-coupled receptor ligand binding and G alpha (i) signaling events. Conclusion: Our study elucidates that upregulation of CDC45 is intricately associated with immune cell infiltration and holds promising potential as a favorable prognostic marker and a novel diagnostic biomarker for GC.

Long-term outcomes after conservative and EDAS treatment for 111 elderly patients with moyamoya disease: longitudinal and cross-sectional study.

OBJECTIVE: This study aimed to explore the clinical features of moyamoya disease (MMD) and the efficacy of encephaloduroarteriosynangiosis (EDAS) in elderly patients with MMD and to identify the risk factors for long-term stroke events. METHODS: Clinical data were retrospectively collected on elderly patients with MMD (age ≥ 60 years) who had been treated at the authors' center from May 2007 to December 2017. Clinical features, angiographic findings, and long-term outcomes (> 5-year follow-up) were analyzed. Cox regression analysis was performed to determine the risk factors for postoperative stroke events. Long-term stroke events were analyzed using Kaplan-Meier curves. RESULTS: The mean age at symptom onset was 62.9 ± 3.0 years among 111 elderly patients with MMD. Vascular comorbidities were present in 80 (72.1%) patients. The ratio of female to male patients was 1:1.2. Familial MMD was found in 7 (6.3%) patients. Cerebral ischemia was the most common clinical manifestation observed in 82 (73.9%) patients. Most patients (59.5%) presented with Suzuki stages 5 and 6 MMD, and 29 (26.1%) patients presented with stenosis or occlusion of the posterior circulation. Unilateral MMD was present in 17 (15.3%) patients. Among the 58 (52.3%) patients who underwent EDAS, 28 (48.3%) and 30 (51.7%) underwent bilateral and unilateral surgeries, respectively. Overall, 53 (47.7%) patients were treated conservatively using internal medicine. After a median follow-up duration of 8.2 years, stroke incidence in the EDAS and conservative treatment groups was respectively 17.2% (7 and 3 cases of cerebral infarction and hemorrhage, respectively) and 49.1% (22 and 4 cases of cerebral infarction and hemorrhage, respectively). The stroke incidence rate was higher in the conservative group than in the EDAS group, with a statistically significant difference (p = 0.001) according to results of the Kaplan-Meier analysis. The identified predictor of postoperative stroke events was initial hemorrhage in the EDAS group and advanced age, aneurysm, and initial ischemia in the conservative treatment group. CONCLUSIONS: The postoperative long-term stroke rate among elderly patients with MMD was lower in the EDAS group than in the conservative treatment group. Long-term stroke events were associated with advanced age, aneurysm, and initial ischemia after conservative treatment and only initial hemorrhage after EDAS.