Complete elimination of hyperleukocytosis risk in AML through early high-quality disease remission.

Background: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is a severe medical emergency associated with high mortality rates and poor prognosis. Prompt and urgent treatment is crucial to address this medical emergency. This study aims to elucidate appropriate diagnostic thresholds for HL and investigate underlying mechanisms and potential targeted therapies. Methods: X-tile software was employed to analyze white blood cell (WBC) count thresholds in AML patients using data from TCGA and TARGET AML databases. METASCAPE and Gene Set Enrichment Analysis (GSEA) were conducted to explore the molecular mechanisms underlying HL in AML. Potential molecular targeted drugs were identified using the CELLMINER platform. Results: Analysis revealed that a WBC count threshold of 75×109/L, rather than the conventional 100×109/L, is more appropriate for diagnosing HL in adult AML patients. This revised threshold could aid clinicians in identifying a greater number of patients requiring immediate intervention. Significant correlations were observed between HL and specific mutations, including NPM1, FLT3, and DNMT3A. For pediatric AML patients, the HL threshold was determined to be 165×109/L. Achieving complete remission (CR) or deeper levels of remission significantly reduces the risks associated with HL. The reduction in risk can lead to survival outcomes for HL patients that are comparable to those of non-hyperleukocytosis patients. Differential gene expression analysis indicated that downregulation of cell adhesion molecules is implicated in HL pathogenesis. Potential targeted therapies for AML with HL include Bcl2 inhibitors and histone deacetylase inhibitors. Clinical observations demonstrated that the addition of Bcl2 inhibitors, such as Venetoclax, to standard therapy results in a rapid reduction in WBC counts, thereby reducing tumor burden and providing prompt symptom relief. Combining these targeted drugs with conventional therapies appears promising in mitigating risks associated with HL. Conclusions: Lower diagnostic thresholds for HL in AML, identifies critical genetic correlations, and highlights effective molecular targeted therapies. Proactive early treatment is crucial for achieving deep remission and reducing HL risk. Future therapeutic strategies should consider integrating molecular targeted drugs with conventional therapies to improve outcomes for patients facing this high-risk hematological emergency.

Spatial correlation between electricity generation and economic scale in Africa.

This study attempts to determine whether there is a spatial correlation between electricity generation and economic scale promoting coordinated development in Africa. We explore the spatial similarity and gray correlation degree between electricity generation and economic scale in Africa since the 21st century by adopting barycenter coupling and Gray Correlation Analysis method. We argue that there is a strong correlation between electricity generation and economic scale. Our findings indicate a significant spatial difference in electricity generation, mainly concentrated in Northern and Southern Africa. Furthermore, spatial pattern remains largely consistent over time, mirroring trends observed at the economic scale. Electricity generation and economic scale were concentrated in six countries- South Africa, Egypt, Algeria, Nigeria, Morocco, and Libya- and did not change significantly over time. A correlation analysis between electricity generation and the economic scale further confirmed this, with a linear coefficient of 0.907. Both the gravity centers of economic scale and electricity generation in Africa move farther in the north-south direction than in the East-West direction, with the former showing a Southwest-Northeast-Southwest track feature and the latter a Northeast-Southwest track feature. The spatial distribution of the gravity centers of electricity generation and the gravity centers of the economic scale in Africa are highly consistent; electricity generation highly correlates with the economic scale, consistent with the research conclusion obtained by the Gray Correlation Analysis method. This study suggests the coordinated development of electricity generation and economic scales in various African countries.

Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy.

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse. Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function. However, there is currently no consensus on the specific distance of distal resection margin.

Green Technology Transfer, Environmental Regulation, and Regional Green Development Chasm: Based on the Empirical Evidence from Yangtze River Delta.

In the face of achieving the overall goal of emission peak and carbon neutrality, strengthening green technology transfer and environmental regulation is the key to narrowing the green technology gap and green development chasm between regions. This paper integrates green technology transfer, environmental regulation, and the green development chasm into one model, and analyzes the mechanism by which green technology transfer and environmental regulation impact the green development chasm. An empirical test was conducted by employing green technology transfer patent and panel data of the Yangtze River Delta from 2005-2019. The results are as follows: (1) Although the green development chasm still exists in the Yangtze River Delta, green technology transfer and environmental regulation have a positive impact on narrowing the regional green development chasm. Especially, the superposition of green technology transfer and environmental regulation can effectively make up for the lack of government and market regulation, and significantly promote the narrowing of the green development chasm. (2) Regional heterogeneity exists and developed regions can achieve the goal of narrowing the green development chasm by relying on green technology transfer or environmental regulation, while less developed regions must rely on the synergy of two dimensions. Thus, the coordination of green technology transfer and environmental regulation must be strengthened. Based on the above research, the main contributions of this paper are to analyze the theoretical mechanism of green technology transfer, environmental regulation, and regional green development chasm, to provide a theoretical and empirical basis for realizing the overall goal of regional green development, and suggestions for optimizing China's current policies.

Current status and future perspectives on neoadjuvant therapy in gastric cancer.

Gastric cancer, with high morbidity and mortality rates, is one of the most heterogeneous tumors. Radical gastrectomy and postoperative chemotherapy are the standard treatments. However, the safety and efficacy of neoadjuvant therapy (NAT) need to be confirmed by many trials before implementation, creating a bottleneck in development. Although clinical benefits of NAT have been observed, a series of problems remain to be solved. Before therapy, more contributing factors should be offered for choice in the intended population and ideal regimens. Enhanced computed tomography (CT) scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors (RECIST), yet CT scanning results sometimes differ from pathological responses. After NAT, the appropriate time for surgery is still empirically defined. Our review aims to discuss the abovementioned issues regarding NAT for GC, including indications, selection of regimens, lesion assessment and NAT-surgery interval time.

An Innovative Prognostic Model Based on Four Genes in Asian Patient with Gastric Cancer.

PURPOSE: Gastric cancer (GC) has substantial biological differences between Asian and non-Asian populations, which makes it difficult to have a unified predictive measure for all people. We aimed to identify novel prognostic biomarkers to help predict the prognosis of Asian GC patients. MATERIALS AND METHODS: We investigated the differential gene expression between GC and normal tissues of GSE66229. Univariate, multivariate and Lasso Cox regression analyses were conducted to establish a four-gene-related prognostic model based on the risk score. The risk score was based on a linear combination of the expression levels of individual genes multiplied by their multivariate Cox regression coefficients. Validation of the prognostic model was conducted using The Cancer Genome Atlas (TCGA) database. A nomogram containing clinical characteristics and the prognostic model was established to predict the prognosis of Asian GC patients. RESULTS: Four genes (RBPMS2, RGN, PLEKHS1, and CT83) were selected to establish the prognostic model, and it was validated in the TCGA Asian cohort. Receiver operating characteristic analysis confirmed the sensitivity and specificity of the prognostic model. Based on the prognostic model, a nomogram containing clinical characteristics and the prognostic model was established, and Harrell's concordance index of the nomogram for evaluating the overall survival significantly higher than the model only focuses on the pathologic stage (0.74 vs. 0.64, p < 0.001). CONCLUSION: The four-gene-related prognostic model and the nomogram based on it are reliable tools for predicting the overall survival of Asian GC patients.

Characteristics of cancer susceptibility genes mutations in 282 patients with gastric adenocarcinoma.

OBJECTIVE: To reveal the distribution signature of cancer susceptibility genes in patients with gastric adenocarcinoma, offering a diagnostic and prognostic surrogate for disease risk management and therapeutic decisions. METHODS: A total of 282 patients with gastric adenocarcinoma (182 males and 100 females) were enrolled in this study, with peripheral blood genomic DNA extracted. Mutations of 69 canonical cancer susceptibility genes or presumably tumor-related genes were analyzed by targeted capture-based high-throughput sequencing. Candidate mutations were particularly selected for discussion on tumor pathogenesis according to the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: In this study, 7.1% (20/282) of patients with gastric adenocarcinoma were found to harbor mutations of canonical or presumable cancer susceptibility genes. The detection rate in male patients (3.8%, 7/182) was significantly lower than that in female patients (13%, 13/100) (P=0.004). The most recurrent mutations were in A-T mutated (ATM) (1.1%, 3/282), followed by BRCA1, BRIP1 and RAD51D, all showed a detection rate of 0.7% (2/282). Mutations in three genes associated with hereditary gastric cancer syndromes were detected, namely, PMS2 and EPCAM associated with Lynch syndrome and CDH1 associated with hereditary diffuse gastric cancer. The detection frequencies were all 0.4% (1/282). Notwithstanding no significant difference observed, the age of patients with pathogenic mutations or likely pathogenic mutations is slightly younger than that of non-carriers (median age: 58.5 vs. 60.5 years old), while the age of patients with ATM mutations was the youngest overall (median age: 49.3 years old). CONCLUSIONS: Our study shed more light on the distribution signature and pathogenesis of mutations in gastric cancer susceptibility genes, and found the detection rate of pathogenic and likely pathogenic mutations in male patients was significantly lower than that in female patients. Some known and unidentified mutations were found in gastric cancer, which allowed us to gain more insight into the hereditary gastric cancer syndromes from the molecular perspective.

Prognostic value and nomograms of proximal margin distance in gastric cancer with radical distal gastrectomy.

OBJECTIVE: The proximal margin (PM) distance for distal gastrectomy (DG) of gastric cancer (GC) remains controversial. This study investigated the prognostic value of PM distance for survival outcomes, and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram. METHODS: Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery, Nanfang Hospital, Southern Medical University were included. The first endpoints of the prognostic value of PM distance (assessed in 0.5 cm increments) for disease-free survival (DFS) and overall survival (OS) were assessed. Multivariate analysis by Cox proportional hazards regression was performed using the training set, and the nomogram was constructed, patients were chronologically assigned to the training set for dates from June 1, 2004 to January 30, 2012 (n=493) and to the validation set from February 1, 2012 to June 30, 2014 (n=211). RESULTS: Among 704 patients with pTNM stage I, pTNM stage II, T1-2, T3-4, N0, differentiated type, tumor size ≤5.0 cm, a PM of (2.1-5.0) cmvs. PM≤2.0 cm showed a statistically significant difference in DFS and OS, while a PM>5.0 cm was not associated with any further improvement in DFS and OSvs. a PM of 2.1-5.0 cm. In patients with pTNM stage III, N1, N2-3, undifferentiated type, tumor size >5.0 cm, the PM distance was not significantly correlated with DFS and OS between patients with a PM of (2.1-5.0) cm and a PM≤2 cm, or between patients with a PM >5.0 cm and a PM of (2.1-5.0) cm, so there were no significant differences across the three PM groups. In the training set, the C-indexes of DFS and OS, were 0.721 and 0.735, respectively, and in the validation set, the C-indexes of DFS and OS, were 0.752 and 0.751, respectively. CONCLUSIONS: It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease, while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease. Different types of patients should be considered for removal of an individualized PM distance intra-operatively. We developed a universally applicable prediction model for accurately determining the 1-year, 3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.

Gastric cancer: Epidemiology, risk factors and prevention strategies.

Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in Helicobacter pylori (H. pylori) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors. H. pylori infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.

Low expression of miR-125a-5p is associated with poor prognosis in patients with gastric cancer.

microRNAs (miRs) serve critical roles in tumor progression. Low expression of miR-125a in gastric carcinoma (GC) may promote tumor development. In the present study, low expression of miR-125a was confirmed in cancer tissues using The Cancer Genome Atlas database. Additionally, the expression and clinical significance of miR-125a-5p was investigated using reverse transcription-quantitative PCR in 150 cases of GC. The results of the present study demonstrated that the level of miR-125a-5p expression was decreased in GC biopsies compared with that in matched adjacent normal tissues. Low expression of miR-125a-5p was associated with increased tumor diameter, high Ki67 expression and poor overall survival of patients with GC. Multivariate survival analysis demonstrated that low miR-125a-5p expression may be used as an independent prognostic factor for patients with GC. However, no effects on the cell viability in a Cell Counting kit-8 assay, and cell migration and invasion in Transwell assays were detected in response to treatment using miR-125a-5p mimics or inhibitors in vitro. Therefore, the results of the present study provide evidence that low expression of miR-125a-5p may be associated with a poor prognosis, suggesting its value as a tumor biomarker for patients with GC.

Prognostic significance of periostin in colorectal cancer.

Accumulating evidence suggests that periostin is frequently upregulated in tissue injury, inflammation, fibrosis and tumor progression. Periostin expression in cancer cells can promote metastatic potential of colorectal cancer (CRC) via activating PI3K/Akt signaling pathway. Moreover, periostin is observed mainly in tumor stroma and cytoplasm of cancer cells, which may facilitate aggressiveness of CRC. In this review, we summarize information regarding periostin to emphasize its role as a prognostic marker of CRC.

Comparison of Microbiota in Patients Treated by Surgery or Chemotherapy by 16S rRNA Sequencing Reveals Potential Biomarkers for Colorectal Cancer Therapy.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide due to its high difficulty in early diagnosis, high mortality rate and short life span. Recent publications have demonstrated the involvement of the commensal gut microbiota in the initiation, progression and chemoresistance of CRC. However, this microbial community has not been explored within CRC patients after anti-cancer treatments. To this end, we performed next generation sequencing-based metagenomic analysis to determine the composition of the microbiota in CRC patients after anti-cancer treatments. The microbial 16S rRNA genes were analyzed from a total of 69 fecal samples from four clinical groups, including healthy individuals, CRC patients, and CRC patients treated with surgery or chemotherapy. The findings suggested that surgery greatly reduced the bacterial diversity of the microbiota in CRC patients. Moreover, Fusobacterium nucleatum were shown to confer chemoresistance during CRC therapy, and certain bacterial strains or genera, such as the genus Sutterella and species Veillonella dispar, were specifically associated with CRC patients who were treated with chemotherapeutic cocktails, suggesting their potential relationships with chemoresistance. These candidate bacterial genera or strains may have the ability to enhance the dosage response to conventional chemotherapeutic cocktails or reduce the side effects of these cocktails. A combination of common CRC risk factors, such as age, gender and BMI, identified in this study improved our understanding of the microbial community and its compositional variation during anti-cancer treatments. However, the underlying mechanisms of these microbial candidates remain to be investigated in animal models. Taken together, the findings of this study indicate that fecal microbiome-based approaches may provide additional methods for monitoring and optimizing anti-cancer treatments.

Tumor pyruvate kinase M2: A promising molecular target of gastrointestinal cancer.

Gastrointestinal (GI) cancer is one of the most common causes of cancer-related deaths worldwide. Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy. Pyruvate kinase isoform M2 (PKM2), a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate, confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment. In this review, we have summarized current research on the expression and regulation of PKM2 in tumor cells, and its potential role in GI carcinogenesis and progression. Furthermore, we have also discussed the potential of PKM2 as a diagnostic and screening marker, and a therapeutic target in GI cancer.

Template-controlled Sonogashira cross-coupling reactions on a Au(111) surface.

We employed three metal-coordination structures as templates to control the Sonogashira cross-coupling reactions on a Au(111) surface catalyzed by loaded Pd. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for an efficient template: high accessibility of reaction sites, structural rigidity and thermal stability.

HOXC10 up-regulation promotes gastric cancer cell proliferation and metastasis through MAPK pathway.

OBJECTIVE: As an important regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and its expression indicates poor survival outcome. However, very few studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the aim of this study was to determine the role of HOXC10 in gastric cancer and the potential mechanism underlying its function for cancer biology. METHODS: A primary gastric cancer mouse model was obtained via intra-gastric wall injection of gastric cancer cells and was used to evaluate the function of HOXC10 during gastric cancer progression in vivo. Immunohistochemistry was performed to visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells were transfected with plasmids to increase the expression of HOXC10, and siRNA transfection was performed to suppress HOXC10 expression. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were utilized to measure mRNA and protein expression, respectively. Proliferation, migration, and invasion were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, and matrigel invasion assay in vitro, respectively. RESULTS: HOXC10 expression was significantly increased in gastric cancer tissues compared to matched normal tissues. HOXC10 up-regulation significantly increased tumor volumes in nude mice. Plasmid transfection significantly increased HOXC10 protein and mRNA expressions and effectively promoted cell proliferation. Moreover, HOXC10 up-regulation significantly promoted migration and invasion of gastric cancer cells. Mechanistic investigation showed that HOXC10 up-regulation significantly increased mRNA and protein expression of mitogen-activated protein kinase (MAPK) signaling related genes, including c-myc, c-jun and p53, while also modulating the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and P38 but not their total protein levels. CONCLUSIONS: This study demonstrated the tight link between HOXC10 and gastric cancer cell proliferation and metastasis via involvement of the MAPK pathway.

Quasicrystallinity expressed in two-dimensional coordination networks.

The recognition of quasicrystals, which exhibit long-range order but lack translational symmetry, represented both the introduction of a new class of materials and a transformative breakthrough in crystallography. Concomitant with the exploration of quasicrystallinity, metal-organic architectures emerged as promising and versatile systems with significant application potential. Their building principles have been studied extensively and become manifest in a multitude of intricate amorphous and crystalline phases. To date, however, indications for quasicrystalline order have been elusive in metal-organic coordination networks (MOCNs). Here we employ rare-earth-directed assembly to construct a two-dimensional tiling with quasicrystalline characteristics at a well-defined gold substrate. By careful stoichiometry control over europium centres and functional linkers, we produced a porous network, including the simultaneous expression of four-fold, five-fold and six-fold vertices. The pertaining features were directly inspected by scanning tunnelling microscopy, and the molecule-europium reticulation was recognized as square-triangle tessellation with dodecagonal symmetry. Our findings introduce quasicrystallinity in surface-confined MOCNs with a nanoporous structure and anticipate functionalities that arise from quasicrystalline ordering of the coordinative spheres.

Tunable lanthanide-directed metallosupramolecular networks by exploiting coordinative flexibility through ligand stoichiometry.

We report the self-assembly of multi-component lanthanide coordination metallosupramolecular structures on a Au(111) surface. Eu atoms coordinate with two heterotypic ligands of quarterphenyl-4,4''-dicarbonitrile and 4',4''''-(1,4-phenylene)bis(2,2':6',2''-terpyridine). For carbonitrile ligand : terpyridyl stoichiometric ratios of 0.7, Eu atoms are primarily ligated in a four-fold coordination scheme. By increasing the carbonitrile ligand to reach a stoichiometry of 1.8, Eu atoms are ligated now in a five-fold coordination sphere. Two types of coordination schemes result in structures exhibiting one-dimensional and two-dimensional morphologies, respectively. This study demonstrates that the flexible lanthanide coordination sphere facilitates the rational design of metallosupramolecular architectures.

Two-Dimensional Superlattices of Bi Nanoclusters Formed on a Au(111) Surface Using Porous Supramolecular Templates.

We used porous supramolecular structures as templates to make two-dimensional (2D) superlattices of Bi nanoclusters on a Au(111) surface. First, we applied on-surface self-assembly to prepare 2D porous supramolecular structures containing well-ordered nanopores. Then, we deposited Bi atoms on the surface. The Bi atoms were confined in the supramolecular pores and formed nanoclusters of a critical size that is defined by the pore size. These nanoclusters were arranged as a 2D superlattice dictated by the structure of the supramolecular templates. The nanocluster size and superlattice periodicity can be adjusted by appropriately designing the supramolecular structures. We further studied the formation mechanism of the nanoclusters. We found that Bi atoms could diffuse across the pore boundaries at room temperature and nucleated as clusters inside the pores. The clusters grew until they reached the critical size and became stable. We used kinetic Monte Carlo simulations to reproduce the experimental results and quantified the interpore diffusion barrier to be 0.65 eV.