The traditional processing method for paraffin-embedded tissues is time-consuming, while the ultrasonic rapid processing method has a short processing time. However, its effects on tissue proteins, DNA, and RNA remain unclear. This study aims to evaluate the effects of the ultrasonic rapid processing method on proteins, DNA, and RNA in paraffin-embedded tissues through hematoxylin and eosin (HE) staining, immunohistochemical staining, and molecular pathological detection.

Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and remains incurable. Patients with primary refractory multiple myeloma (PRMM) show poor response to initial induction therapy. This study aims to develop a machine learning-based model to predict treatment response in newly diagnosed multiple myeloma (NDMM) patients, in order to optimize therapeutic strategies.

Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making.

To identify the key genes involved in the development and progression of prostate cancer (PCa) and those associated with the prognosis of the malignancy.

To explore the relationship of glutathione S-transferase P1 (GSTP1) and X-ray repair cross-complementation group 1 (XRCC1) gene polymorphisms with chemotherapy sensitivity and prognosis in patients with prostate cancer (PCa).

Malignant mesothelioma is a rare tumor that is highly correlated with asbestos exposure. Due to the insidious early symptoms, mesothelioma is usually diagnosed in the advanced stages of the disease. Therefore, there is an urgent need for some early detection biomarkers to assist in the diagnosis of mesothelioma. The detection of DNA methylation can be one of the new research directions. This article provides a comprehensive discussion on the research progress of DNA methylation in malignant mesothelioma, including genes that can serve as diagnostic markers for malignant mesothelioma and the current problems in clinical application. It also provides new insights for future research directions using DNA methylation as a diagnostic marker for mesothelioma.

To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).

To explore the clinical characteristics and genetic etiology of a patient with De-differentiated liposarcoma (DDLPS).

To review the clinicopathological features of TFE3-rearranged renal cell carcinoma (TFE3-RCC) with venous tumor thrombus (VT) (TFE3-VT), to explore treatment strategies and to prognostic characteristics, and to provide diagnostic and therapeutic references for TFE3-VT patients.

To investigate the relationship between oxidative stress-related genes and prostate cancer (PCa) from a multi-omics perspective using summary-data-based Mendelian randomization (SMR), colocalization analysis, and cellular experiments.

Immunotherapy based on immune checkpoint inhibitor (ICI) has shown remarkable efficacy in the treatment of microsatellite instability (MSI)-high CRC. However, the monotherapy of ICI in microsatellite stable (MSS) CRC has not been satisfactory. Some patients with MSS CRC can benefit from various combination immunotherapy regimens. Identifying appropriate biomarkers to select MSS-type CRC patients who will benefit from ICI treatment prior to therapy initiation and dynamically monitoring treatment efficacy during the therapeutic course have become crucial components of precision medicine in clinical practice. This article reviews the current research status of traditional biomarkers such as tumor mutation burden (TMB) and PD-L1 expression. It also explores the latest research progress and clinical translation potential of emerging biomarkers, including POLE/POLD1 mutations, immune score, circulating tumor DNA, and gut microbiome. Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.

To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL).

Objective: To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL). Methods: A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children's Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children's Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis. Results: The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children's Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months). Conclusions: Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objectives: To investigate the expression of signal-induced proliferation-associated 1 (SIPA1) in colorectal cancer tissues and its relationship with patient prognosis. To explore the effects of SIPA1 on proliferation and migration abilities, as well as the possible molecular mechanisms. Methods: Using The Cancer Genome Atlas (TCGA) database to analyze the differential expression of SIPA1 and conduct survival analysis. Then, plotting receiver operating characteristic curve (ROC) and prognosis calibration curve analysis to assess the predictive capability and accuracy of SIPA1 for patient prognosis. Subsequently, verifying the expression levels of SIPA1 in tumor tissues and adjacent normal tissues using immunohistochemistry (IHC) and western blot (WB) assays(from March 1, 2023, to May 1, 2024, pathological specimens of five colorectal cancer patients were selected from the tissue bank of affiliated hospital of Nantong University. tissue microarrays were constructed using both cancerous tissues and adjacent normal tissues), and exploring the correlation between SIPA1 and clinical pathological parameters. Next, establishing SIPA1 stable knockdown cell lines in colorectal cancer cell lines DLD1 and HCT116, and assessing the biological behavior changes of tumor cells after SIPA1 knockdown through cell proliferation, invasion, and migration experiments. Validating the impact of SIPA1 on colorectal cancer cell proliferation in vivo through subcutaneous xenograft experiments in nude mice. Exploring the potential pro-tumor mechanisms of SIPA1 through pathway enrichment analysis, and confirming these using WB experiments. The proliferation, invasion and migration of tumor cells were detected after adding PI3K activator. Lastly, conducting correlation analysis between SIPA1 and immune checkpoint, as well as the association with immune cells in the tumor microenvironment. Results: Differential analysis showed that mRNA expression of SIPA1 in colorectal cancer tissues was significantly higher than that in adjacent normal tissues (P＜0.05). Prognostic analysis indicated that patients with high expression of SIPA1 had poor overall survival (P＜0.001), and the expression level of SIPA1was correlated with lymph node invasion (P＜0.001) and N stage (P＜0.05). ROC curve and prognosis calibration curve suggest that SIPA1 can effectively predict five-year survival rate of patients (AUC=0.7), and the predictive performance of the model is relatively accurate (P＜0.001). WB experiments showed a significant increase in the expression level of SIPA1 protein in colorectal cancer specimens (P＜0.001). Immunohistochemistry results indicated higher staining scores of SIPA1 in tumor tissues. In vitro experiments demonstrated that SIPA1 knockdown significantly inhibited the proliferation, invasion, and migration capabilities of colorectal cancer cells. In DLD1 and HCT116 cells, the SIPA1-knockdown group exhibited significantly lower absorbance compared to the control group (0.89±0.01 vs. 1.57±0.02 and 0.72±0.01 vs. 1.31±0.03, respectively, both P＜0.001). The SIPA1-knockdown group also demonstrated a reduced number of migrated cells relative to the control group (197.93±16.64 vs. 518.48±29.15 and 171.83±12.49 vs. 446.00±21.81, respectively, both P＜0.001). Furthermore, the cell wound-healing rate was significantly lower in the SIPA1-knockdown group than that in the control group [(0.32±0.01)% vs. (0.61±0.01)% and (0.28±0.01)% vs. (0.75±0.01)%, respectively, both P＜0.001]. In vivo animal experiments suggested that SIPA1 knockdown could inhibit tumor growth [(460.35±57.47) mm³ vs (1 177.55±208.24)mm³, (0.76±0.11)g vs (1.43±0.08)g, P＜0.05]. Pathway enrichment analysis revealed significant enrichment of the receptor tyrosine kinase signaling pathway, and SIPA1 knockdown could inhibit the activation of the phosphatidylinositide 3-kinases (PI3K)/protein kinase B (PKB)/glycogen synthase kinase-3β (GSK3β) signaling pathway. The PI3K activator reversed the inhibitory effect of SIPA1 silencing on tumor cell proliferation, invasion and migration. Correlation analysis indicated that high expression of SIPA1 was associated with immune checkpoints and various immunosuppressive cells (all P＜0.05). Conclusions: SIPA1 is highly expressed in colorectal cancer and associated with poor prognosis. SIPA1 may affect the proliferation and migration abilities of tumor cells by regulating the PI3K/AKT/GSK3β signaling pathway.

Objective: To investigate the effect of miR-1-3p on mitophagy in human esophageal squamous cell carcinoma (ESCC) cells and the related mechanisms. Methods: The differentially expressed miRNAs in ESCC were screened using the GEO database. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure miR-1-3p expression in normal esophageal epithelial cells (HET-1A) and ESCC cell lines (TE1, KYSE30, KYSE150, KYSE410, Eca109). Bioinformatics tools were utilized to predict target genes of miR-1-3p, subcellular localization was confirmed by fluorescence in situ hybridization. The targeting relationship between miR-1-3p and SLC7A11 was validated using dual-luciferase reporter assay. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Furthermore, experimental validation demonstrated that overexpression of SLC7A11 rescued the presence of the miR-1-3p/SLC7A11 axis. Confocal microscopy was used to detect changes in mitochondrial autophagic lysosomes, while transmission electron microscopy was employed to observe mitophagy and morphological alterations. Western blot was conducted to evaluate the expression of autophagy-related proteins LC3 and P62. Flow cytometry was used to measure mitochondrial membrane potential and reactive oxygen species (ROS). Immunohistochemistry was applied to assess SLC7A11 expression in 133 ESCC patient tissues and 115 normal esophageal epithelial tissues. The correlation between SLC7A11 expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for multivariate analysis. Results: The expression of miR-1-3p in ESCC cells was significantly lower than that in HET-1A cells (P＜0.05). SLC7A11 was a target gene of miR-1-3p. Transfection of miR-1-3p mimic inhibited the proliferation of ESCC cells. CCK-8 assay results showed that the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic group (absorbance values: 2.88±0.24 and 2.88±0.18, respectively) was significantly lower than that in the miRNA mimic negative control (NC) group (3.94±0.27, P＜0.001; 4.20±0.21, P＜0.001). Meanwhile, the proliferative capacity of KYSE30 and KYSE410 cells in the miR-1-3p mimic+SLC7A11-overexpression (OE) group (absorbance values: 3.57±0.15 and 3.60±0.13, respectively) was significantly higher than that in the miR-1-3p mimic +empty vector (EV) group (2.54±0.10, P＜0.001, 2.36±0.16, P＜0.001). Additionally, transfection of miR-1-3p mimic promoted apoptosis. Flow cytometry results demonstrated that the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic group [(9.22±0.05)% and (6.55±0.37)%, respectively] were significantly higher than those in the miRNA mimic NC group [(0.81±0.17)%,P＜0.001); (1.04±0.12)%, P＜0.001]. Conversely, the apoptosis rates of KYSE30 and KYSE410 cells in the miR-1-3p mimic + SLC7A11-OE group [(0.73±0.04)% and (1.19±0.05)%, respectively] were significantly lower than those in the miR-1-3p mimic+EV group [(9.83±0.41)%, P＜0.001); (6.09±0.17)%, P＜0.00)]. MiR-1-3p mimic downregulated SLC7A11 protein expression and the LC3Ⅱ/LC3I ratio (P＜0.05), upregulated P62 protein expression (P＜0.05), this phenomenon can be rescued by overexpressing SLC7A11 (P＜0.05). Additionally, miR-1-3p mimic increased ROS levels and decreased mitochondrial membrane potential (JC-1 aggregate/monomer ratio), this phenomenon can be rescued by overexpressing SLC7A11 (P＜0.05). SLC7A11 expression was higher in ESCC tissues compared to normal esophageal epithelial tissues (P＜0.001), and SLC7A11 serves as an independent prognostic factor in ESCC (HR=2.15, 95% CI: 1.27-3.65, P=0.004). Conclusion: miR-1-3p inhibits mitophagy in esophageal squamous cell carcinoma by targeting SLC7A11.

To observe the effect of wheat-grain moxibustion plus chemotherapy on the activities of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling and expressions of Caspase-3 and Caspase-9 in mice with breast cancer, so as to explore its mechanisms underlying suppression of tumor growth.

This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.