Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

The novel HLA-DPB1*1352:01 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*1352:01 differs from HLA-DPB1*02:01:02:01 by one nucleotide in exon 4.

Primary isolated central nervous system acute lymphoblastic leukemia with BCR-ABL1 rearrangement: A case report.

BACKGROUND: BCR-ABL1 fusion gene is associated with a poor prognosis and a high incidence in central nervous system (CNS) leukemia. CNS invasion which detected at the initial diagnosis is commonly with bone marrow infiltration. It is uncommon for the leukemia cells to be located primarily in the CNS without bone marrow involvement. CASE SUMMARY: We here report the rare initial presentation of CNS-restricted BCR-ABL-positive acute lymphoblastic leukemia in a 30-year-old female patient who clinically manifested with leukemic meningitis, with no involvement in peripheral blood or bone marrow. Identification of abnormal phenotypes of blast cells, and BCR-ABL1 rearrangement in the cerebrospinal fluid alone established the diagnosis of primary CNS-isolated acute lymphocytic leukemia. The patient received a combination of intrathecal therapy and high-dose chemotherapy. But the benefits of the treatments were short-lived and she experienced recurrence. CONCLUSION: Flow cytometry in combination with molecular genetic analysis improved diagnostic accuracy. New approaches that may enhance the efficacy of the existing therapies and cure CNS leukemia are required.

[Comparision of Allogeneic Hematopoietic Stem Cell Transplantation between Children with Thalassemia of Different Ages].

OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION: Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.

[The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia].

OBJECTIVE: To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients. METHODS: The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed. RESULTS: Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively. CONCLUSION: The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Assessment of the Probability of Post-thrombotic Syndrome in Patients with Lower Extremity Deep Venous Thrombosis.

This study was performed to assess the probability of post-thrombotic syndrome (PTS) after treatment of lower extremity deep venous thrombosis (LEDVT). Patients with LEDVT undergoing their first treatments in Nanjing First Hospital from January 2013 to December 2014 were enrolled in this study (156 patients were enrolled in the training cohort, and 135 patients were enrolled in the validation cohort). 51 and 45 patients developed PTS in the two cohorts, respectively. Independent risk factors for PTS were investigated in the training cohort, and these independent risk factors were employed to develop the APTSD scoring system with which to predict the probability of PTS. Four independent risk factors for PTS were identified: iliac vein compression syndrome, residual iliac-femoral vein thrombosis, residual femoral-popliteal vein thrombosis and insufficient anticoagulation. Patients in the training cohort were divided into 2 groups according to the APTSD score of ≤7.0 and >7.0 points regarding the probability of PTS (median PTS-free time, 21.82 vs. 18.84 months; P < 0.001). The accuracy of this score system was 81.7% for the training cohort and 82.5% for the validation cohort. Patients with an APTSD score of >7.0 points may have an increased probability of developing PTS.

[Efficacy of drug-coated balloon and common balloon for treatment of superficial femoral artery and popliteal artery arteriosclerosis obliterans: prospective randomized controlled triac].

OBJECTIVE: To compared the efficacy of drug-coated balloon and common balloon for treatment of superficial femoral artery and popliteal artery occlusive disease. METHODS: Forty-six patients were admitted for ipsilateral single or multiple superficial femoral artery and/or popliteal artery lesions (between 3 and 15 cm stenosis or occlusion), Rutherford grades 2 to 5, with or without other accompanying diseases in the Department of Interventional Vascular Therapy of the First Hospital of Nanjing between September, 2015 and December, 2016. The patients were randomly assigned into drug-coated balloon (DCB) group (n=23) and common balloon (CB) group (n=23). None of the patients had stent restenosis, aneurysms, acute thrombosis, pregnancy, life expectancy less than 1 year, or below-the-knee artery occlusion. The late lumen loss (LLL), improvement of the ankle brachial index (ABI), improvement of Rutherford grade, incidence of restenosis, thrombosis rate and amputation rate were compared between the two groups at 6 months after treatment. RESULTS: The two groups of patients were comparable for general conditions, risk factors, and characteristics of the compromised vessels (P>0.05). Six months after treatment, the patients in DCB group showed significantly smaller LLL, more obvious improvement of the ABI and Rutherford grade, and lower restenosis rate and thrombosis rate than those in CB group (P<0.05). The amputation rates were similar between the two groups (P>0.05). CONCLUSIONS: DCB shows obvious advantages over common balloon for treatment of superficial artery and popliteal artery arteriosclerosis obliterans in that it more effectively reduces LLL, restenosis rate and thrombosis rate and improves the ABI and Rutherford grade at 6 months after the treatment.

Carfilzomib Inhibits Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells and Leads to the Induction of Apoptosis.

Mantle cell lymphoma (MCL) remains incurable and new treatments are needed, especially in the relapsed/refractory setting. We therefore investigated the effects of carfilzomib, a novel, long-acting, second-generation proteasome inhibitor, in MCL cells. Eight established MCL cell lines and freshly isolated primary MCL cells were treated with carfilzomib. Cell proliferation was assessed by a 3H-thymidine incorporation assay. Cell apoptosis was evaluated by flow cytometry with annexin V and propidium iodide. Electrophoresis mobility shift (EMSA), Western blot, and luciferase assays were used to analyze NF-κB activation and related signaling proteins. Carfilzomib inhibited growth and induced apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells occurred in a caspase-dependent manner through both intrinsic and extrinsic caspase pathways. In addition, carfilzomib inhibited constitutive activation of the NF-κB signaling cascade, both in MCL cell lines and primary MCL cells, by completely blocking the phosphorylation of IκBα. Our results demonstrate that carfilzomib can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway.

[Effect of SAHA on Maturation of Dendritic Cells and Its Mechanism].

OBJECTIVE: To investigate the effect of SAHA on the maturation of human dendritic cells (DC) and to explore its underlying mechanism. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from human peripheral blood and cultured in RPMI 1640 medium with 100 ng/ml rhGM-CSF and 500 U/ml rhIL-4. In the LPS induced maturation process, dendritic cells treated with or without SAHA were used as test group, and dendritic cells treated without LPS or SAHA were used as control group. DC was observed under inverted microscope. Flow cytometer was used to detect the surface antigen molecules expressed by DC. The mixed lymphocyte culture (MLC) was used to observe the allogeneic lymphocyte stimulation. The NF-κB signaling pathway was detected by electrophoretic mobility shift assay (EMSA). RESULTS: The SAHA could effectively suppress the maturation of DC induced by LPS, the DC treated with SAHA+LPS had immature morphological characteristics; the expression of CD80, CD83 and HLA-DR in SAHA+LPS group and control group were significantly down-regulated as compared with single LPS group (P<0.01); the ability of DC to stimulate the proliferation of allogeneic T lymphocytes in SAHA+LPS group and control group was significantly weaker than that in single LPS group (P<0.01); EMSA results showed that NF-κB activity decreased after SAHA and LPS treatment and was significantly lower than that of single LPS group. CONCLUSION: SAHA can effectively suppress DC maturation induced by LPS and also weaken the ability to stimulate allogeneic T lymphocyte. NF-κB signaling pathway is involved in regulating DC maturation.

[Expression of FoxO3a in patients with acute myeloid leukemia and its clinical significance].

This study was aimed to investigate the expression and clinical significance of forkhead box protein O3a (FoxO3a) in the patients with acute myeloid leukemia (AML). Western blot was used to detect the FoxO3a protein expression in bone marrow samples from 44 newly diagnosed AML patients and 5 healthy donors. Additionally, 14 patients' samples were reevaluated when they got complete remission (CR). The results showed that FoxO3a expression (FoxO3a/ß-actin 0.43 ± 0.19) in newly diagnosed AML patients was much higher than that in healthy donors (FoxO3a/ß-actin 0.19 ± 0.06) (P < 0.001). The FoxO3a level was down-regulated when CR was got and there was not significant difference between patients in CR and healthy donors (P > 0.10). The correlation analysis showed that the level of FoxO3a expression positively correlated with the white blood cell count of AML patients at the time of diagnosis. Although FoxO3a expression did not positively correlate with the CR rate, the higher FoxO3a expression in AML patients showed a shorter remission duration. It is concluded that FoxO3a may be a oncoprotein in AML, and the high FoxO3a expression is associated with poor prognosis.