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Acute myeloid leukemia (AML) is a large class of heterogeneous hematological malignancies with the highest incidence rate in acute leukemia. Its pathogenesis is still unclear, which may be related to genetics. According to the latest AML NCCN guidelines, genes involved in AML family genetic changes include RUNX1, ANKRD26, CEBPA. Finding new genes related to AML genetics is of great significance for predicting the prognosis of patients, developing targeted drugs, and selecting transplant donors. Here, we report a case of adult female AML patient whose three relatives suffered from hematological malignancies, including Waldenstrom macroglobulinemia, NK/T-cell lymphoma, and angioimmunoblastic T-cell lymphoma. The screen for genetic susceptibility genes related to blood and immune system diseases was carried out, and the result showed that the patient herself, her son, her daughter, and her two cousins all had STK11 p.F354L and/or THBD p.D486Y mutations. At present, there is no research or case report on the relationship between STK11/THBD and family aggregation of hematological malignancies. We report for the first time that an AML patient with STK11 and THBD mutations has a family aggregation of hematological malignancies, and consider that STK11 and THBD may be related to family genetic changes which ultimately cause the family aggregation of hematological malignancies.

Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.

The standardized treatment plan for patients with plasmablastic lymphoma (PBL) remains controversial. Taking morphological characteristics and immunophenotypes into consideration may provide superior options for the treatment of PBL. In this case, we report that a myeloma-type regimen containing bortezomib plus cyclophosphamide, epirubicin, vindesine and prednisolone (CDOP) followed by sequential autologous hematopoietic stem cell transplantation (ASCT) and lenalidomide-based maintenance therapy to treat PBL may represent a promising regimen to improve the prognosis.

Background: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. Methods: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. Results: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)‐CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. Conclusion: Routine chest CT is needed for breast cancer patients before surgery, and PET‐CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer. [ABSTRACT FROM AUTHOR]

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3+CD8+ CTLs through immune stimulation. These CD3+CD8+ CTLs could effectively recognize and induce the apoptosis of human Kasumi-3 AML cells. In addition, cytarabine-induced AML cell apoptosis was enhanced by CTL treatment. Western blotting revealed that Bcl-2 expression was downregulated in AML cells following cytarabine and CTL treatment, indicating that the synergistic effect of this treatment on AML cell apoptosis is due to the downregulation of Bcl-2. These results highlight the potential application of CTL immunotherapy for the treatment of AML. Further studies optimizing the specificity and potency of CTLs, and identifying favorable combinations with other chemotherapeutic drug are required. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV-specific T cells by immune stimulation ex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL. [ABSTRACT FROM AUTHOR]

Aimed at the poor toughness of chitosan hemostatic membrane, glycerol and etamsylate were chosen as modification reagents to prepare chitosan (CS)/carboxymethyl chitosan (CMCS) hemostatic membrane with different weight ratios by solution casting method. The effects of glycerol and etamsylate on mechanical properties and hemostatic efficiency were evaluated by tensile tests. The blood coagulation time was characterized to illustrate the interactions between CS/CMCS hemostatic membrane and blood. Results indicate that the elongation at break of CS/CMCS hemostatic membrane modified by glycerol without etamsylate is increased by 4 - 7 times, although the tensile strength of that is decreased by 70%. The tensile strength and the elongation at break of CS/CMCS hemostatic membrane modified by glycerol and etamsylate are 10. 4 ± 0.9MPa and 50. 4 ± 4.5%, respectively. Compared with the CS/CMCS hemostatic membrane modified by glycerol without etamsylate, the tensile strength is increased by 55% and the elongation at break is merely decreased by about 24% attributed to the ions crosslinking of sulfonate. Results of the hemostatic test show that CS/CMCS = 8/2 hemostatic membrane modified by glycerol can accelerate the blood separation and induce the blood coagulation to form black clotting. [ABSTRACT FROM AUTHOR]

Patients with recurrent neuroblastoma (NB) have a broad range of prognoses. This research aimed to develop a nomogram to assess post-recurrence survival (PRS) in patients with recurrent neuroblastoma. The TARGET database was utilized to enroll 825 individuals diagnosed with neuroblastoma between 1986 and 2012, 250 of whom were diagnosed with recurrent NB. These patients were randomly divided into a training group (n = 175) and a validation group (n = 75) at a ratio of 7:3. The Kaplan-Meier method was used for survival analysis. A prognosis nomogram was constructed based on post-recurrence survival indicators identified through Cox regression and LASSO analysis. The nomogram's capability for classification and calibration was assessed using the calibration curve, the area under the time-dependent receiver operating characteristic curve (AUC), and the consistency index (C-index). The nomogram was verified in the validation cohort, and its clinical applicabilities were assessed using the decision curve analysis (DCA). Four PRS predictors, COG risk group, INSS stage, MYCN status, and age, were identified to construct the nomogram, which showed good discrimination and calibration in the training and validation sets. The C-index of the training and validation sets was 0.681 [95% confidence interval (CI), 0.632-0.730] and 0.666 [95% CI, 0.593-0.739], respectively. The nomogram's AUC values for the training and validation sets at 1, 3, and 5 years were 0.747, 0.775, and 0.782 vs. 0.721, 0.757, and 0.776. The nomogram's AUC values were consistently higher than those of the COG risk groups and INSS stage, indicating that the nomogram had superior differentiation compared to the INSS stage and COG risk group. The DCA curve also demonstrated that the nomogram we developed outperformed conventional COG risk groups and INSS stage regarding clinical advantage. In the present study, we developed and validated a novel nomogram that should facilitate more accurate and personalized assessment of the survival probability of children with relapsed neuroblastoma. This model should assist physicians in their clinical decision-making process., Competing Interests: None., (AJCR Copyright © 2023.)