Table3_A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia.xlsx

Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with poor prognosis. Emerging evidence suggests a close association between AML progression and hypoxia. The purpose of this study was to establish a new risk prognostic model for AML based on hypoxia-related genes, and to explore the mechanisms by which hypoxia-related genes affect the prognosis of AML based on tumor immune microenvironment (TIME) and drug resistance.Methods: The AML patient samples obtained from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were classified into C1 and C2 based on hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct the model. AML patient samples were obtained from the TARGET and The Cancer Genome Atlas (TCGA) databases, serving as the training and the validation sets, and were stratified into high-risk and low-risk group according to the median risk score. The correlations between the model and TIME and anti-tumor drugs were analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive and drug-resistant cell lines were detected by Western blot and real-time PCR.Results: The C1 group with high expression of hypoxia-related genes had lower overall survival (OS). Immune-related signaling pathways were different between C1/C2, and hypoxia was positively correlated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both the training and the validation sets. The high-risk group exhibited lower OS and TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 were highly expressed in relapsed patients and AML drug-resistant cell lines.Conclusion: The established novel risk prognostic model and experiment results offer valuable insights for predicting AML prognosis and guiding drug selection. It also provides a fundamental framework for the mechanisms through which hypoxia impacts AML prognosis by modulating TIME and drug resistance.</p

Table2_A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia.xlsx

Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with poor prognosis. Emerging evidence suggests a close association between AML progression and hypoxia. The purpose of this study was to establish a new risk prognostic model for AML based on hypoxia-related genes, and to explore the mechanisms by which hypoxia-related genes affect the prognosis of AML based on tumor immune microenvironment (TIME) and drug resistance.Methods: The AML patient samples obtained from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were classified into C1 and C2 based on hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct the model. AML patient samples were obtained from the TARGET and The Cancer Genome Atlas (TCGA) databases, serving as the training and the validation sets, and were stratified into high-risk and low-risk group according to the median risk score. The correlations between the model and TIME and anti-tumor drugs were analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive and drug-resistant cell lines were detected by Western blot and real-time PCR.Results: The C1 group with high expression of hypoxia-related genes had lower overall survival (OS). Immune-related signaling pathways were different between C1/C2, and hypoxia was positively correlated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both the training and the validation sets. The high-risk group exhibited lower OS and TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 were highly expressed in relapsed patients and AML drug-resistant cell lines.Conclusion: The established novel risk prognostic model and experiment results offer valuable insights for predicting AML prognosis and guiding drug selection. It also provides a fundamental framework for the mechanisms through which hypoxia impacts AML prognosis by modulating TIME and drug resistance.</p

Table1_A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia.xlsx

Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with poor prognosis. Emerging evidence suggests a close association between AML progression and hypoxia. The purpose of this study was to establish a new risk prognostic model for AML based on hypoxia-related genes, and to explore the mechanisms by which hypoxia-related genes affect the prognosis of AML based on tumor immune microenvironment (TIME) and drug resistance.Methods: The AML patient samples obtained from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were classified into C1 and C2 based on hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct the model. AML patient samples were obtained from the TARGET and The Cancer Genome Atlas (TCGA) databases, serving as the training and the validation sets, and were stratified into high-risk and low-risk group according to the median risk score. The correlations between the model and TIME and anti-tumor drugs were analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive and drug-resistant cell lines were detected by Western blot and real-time PCR.Results: The C1 group with high expression of hypoxia-related genes had lower overall survival (OS). Immune-related signaling pathways were different between C1/C2, and hypoxia was positively correlated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both the training and the validation sets. The high-risk group exhibited lower OS and TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 were highly expressed in relapsed patients and AML drug-resistant cell lines.Conclusion: The established novel risk prognostic model and experiment results offer valuable insights for predicting AML prognosis and guiding drug selection. It also provides a fundamental framework for the mechanisms through which hypoxia impacts AML prognosis by modulating TIME and drug resistance.</p

Table_1_The clinical efficacy and safety of different biliary drainage in malignant obstructive jaundice: a meta-analysis.docx

BackgroundCurrently, percutaneous transhepatic cholangial drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) are commonly employed in clinical practice to alleviate malignant obstructive jaundice (MOJ). Nevertheless, there lacks a consensus regarding the superiority of either method in terms of efficacy and safety.AimTo conduct a systematic evaluation of the effectiveness and safety of PTCD and ERCP in treating MOJ, and to compare the therapeutic outcomes and safety profiles of these two procedures.MethodsCNKI, VIP, Wanfang, CBM, PubMed, Web of Science, Embase, The Cochrane Library, and other databases were searched for randomized controlled trials (RCTs) on the use of PTCD or ERCP for MOJ. The search period was from the establishment of the databases to July 2023. After quality assessment and data extraction from the included studies, Meta-analysis was performed using RevMan5.3 software.ResultsA total of 21 RCTs involving 1,693 patients were included. Meta-analysis revealed that there was no significant difference in the surgical success rate between the two groups for patients with low biliary obstruction (P=0.81). For patients with high biliary obstruction, the surgical success rate of the PTCD group was higher than that of the ERCP group (P 0.05).ConclusionBoth PTCD and ERCP can efficiently alleviate biliary obstruction and enhance liver function. ERCP is effective in treating low biliary obstruction, while PTCD is more advantageous in treating high biliary obstruction.</p

The Critical Role of Anode Work Function in Non-Fullerene Organic Solar Cells Unveiled by Counterion-Size-Controlled Self-Doping Conjugated Polymers

In this work, we demonstrated an effective method to modulate the p-type self-doping effect as well as the molecular energy level of an anionic conjugated polymer, namely PCP-<i>x</i> (<i>x</i> = H, Li, Na, K, Cs) by changing the counterions, and hence developed a series of anode interlayer materials for nonfullerene organic solar cells (NF-OSCs). With the decreasing cation radius, self-doping effect of PCP-<i>x</i> can be enhanced and hence the work function (WF) of the PCP-<i>x</i>-modified anodes can be tuned from 4.78 to 5.11 eV. The photovoltaic performance of NF-OSCs based on J52–2F:IT-4F active layer was significantly affected by the WF of the anodes, and a PCE of 12.8% could be achieved by using the PCP-H-modified ITO anodes. Furthermore, the PCP-<i>x</i>-modified anodes were used to fabricate NF-OSCs with different active layers, including PBDTTT-E-T:IEICO and PBDB-T-2F:IT-4F. It was found that the energetic offsets between WF of the anodes and ionization potential (IP) of the donors should be controlled below 0.1 eV to minimize the loss in photovoltaic performance. This work provides not only an effective method for synthesizing a series of p-type interlayer materials with tunable WF but also an insight on the critical importance of developing anode interlayer materials with high WF

Algorithm Optimization in Methylation Detection with Multiple RT-qPCR

<div><p>Epigenetic markers based on differential methylation of DNA sequences are used in cancer screening and diagnostics. Detection of abnormal methylation at specific loci by real-time quantitative polymerase chain reaction (RT-qPCR) has been developed to enable high-throughput cancer screening. For tests that combine the results of multiple PCR replicates into a single reportable result, both individual PCR cutoff and weighting of the individual PCR result are essential to test outcome. In this opportunistic screening study, we tested samples from 1133 patients using the triplicate Epi proColon assay with various algorithms and compared it with the newly developed single replicate SensiColon assay that measures methylation status of the same <i>SEPT9</i> gene sequence. The Epi proColon test approved by the US FDA (1/3 algorithm) showed the highest sensitivity (82.4%) at a lower specificity (82.0%) compared with the Epi proColon 2.0 CE version with 2/3 algorithm (75.1% sensitivity, 97.1% specificity) or 1/1 algorithm (71.3% sensitivity, 92.7% specificity). No significant difference in performance was found between the Epi proColon 2.0 CE and the SensiColon assays. The choice of algorithm must depend on specific test usage, including screening and early detection. These considerations allow one to choose the optimal algorithm to maximize the test performance. We hope this study can help to optimize the methylation detection in cancer screening and early detection.</p></div

The SensiColon exhibited essentially the same performance as the Epi proColon 2.0 CE assay.

<p>Comparison of the positive detection rate was shown for Epi proColon 2.0 CE and the SensiColon assays in various colorectal diseases. 2/3 algorithm was used for data analysis in Epi proColon 2.0 CE assay, and 1/1 algorithm was used for SensiColon assay. Data was shown for PDR of all stages of CRC, adenoma, polyps, other GI diseases and NED for both assays.</p

Positive detection rate for each CRC stage using different algorithm.

<p>Positive detection rate for each CRC stage using different algorithm.</p

Comparison of the positive detection rate between Epi proColon 2.0 and SensiColon.

<p>Comparison of the positive detection rate between Epi proColon 2.0 and SensiColon.</p

Predictive Value of Stemness Factor Sox2 in Gastric Cancer Is Associated with Tumor Location and Stage

<div><p>Cancer stem cells (CSCs) are thought to be the "root" of cancer. Although stemness-related factors ALDH1A1 and Sox2 have been used as markers to identify gastric CSCs, the expression pattern and significance of these factors in gastric cancer have not been sufficiently demonstrated. In this study, the expressions of ALDH1A1 and Sox2 were detected by immunohistochemistry in 122 gastric cancer specimens. And the correlation between Sox2 or ALDH1A1 expression and clinicopathological parameters and overall survival data were analyzed. The positive rate of ALDH1A1 expression was 60%, but there was no significant difference between survival rates of ALDH1A1-positive and ALDH1A1-negative patients. Sox2 was expressed in 42% of specimens and was associated with poor prognosis of patients (<i>P</i> = 0.015). Stratified analysis showed that Sox2 expression correlated with shorter lifespan only in patients with cardiac gastric cancers (<i>P</i> = 0.002) or stage I or II gastric cancers (<i>P</i> = 0.002); but not in patients with non-cardiac cancers (<i>P</i> = 0.556) or stage III or IV gastric cancers (<i>P = 0</i>.<i>121</i>). Analysis on a database cohort validated the correlation between Sox2 expression and poor prognosis in stage II cancer. Also, expression of Sox2 was associated with lymphnode metastasis in patients with cardiac gastric cancer (<i>P</i> = 0.037). A multivariate analysis revealed that Sox2 was an independent prognostic factor in cardiac gastric cancer. Our results indicate that predictive value of Sox2 in gastric cancer is associated with cardiac cancer location and with early cancer stages (I and II).</p></div