The Upper Permian Changhsing Formation is one of the most important gas-bearing formations in the Eastern Sichuan Basin. Nonetheless, the primary factors controlling the reef-shoal gas reservoirs of ...different regions are diverse. Clarifying the controlling factors for the formation of intra-platform reef-shoal reservoirs will promote the exploration and development process of the Changhsing Formation. By using outcrop data, core observation, thin section identification, scanning electron microscope analysis, physical property study, and logging interpretation, this paper analyse the characteristics and factors controlling the reef-shoal reservoir in Dianjiang area of the Eastern Sichuan Basin. The results show that the reef cap and reef base microfacies fine-to-medium crystalline dolomite reservoir have the best physical properties, and the reservoir spaces are primarily composed of intercrystalline pores, intercrystalline solution pores, karst caves, and fractures. The main lithology of reservoir formation is reef-shoal facies. The results for the carbon and oxygen isotopes show that dolomites of different particle sizes are formed in three environments. Affected by regression in the late Changhsingian Age, the reef-shoal of the Changhsing Formation were subaerially exposed to meteoric water diagenesis environments, resulting in the highly dispersed particles in rocks that formed a honeycomb karst system, which greatly improved the physical properties of the reservoirs. After reflux dolomitization, the honeycomb karst system was well preserved due to strong resistance to pressure and dissolution of dolomite. Therefore, dolomitization in the Changhsing formation contributed to reservoir porosity. Later, tectonic fracturing has adjusted and modified the reef-shoal reservoir. In summary, penecontemporaneous karstification was the key to the formation of the reef-shoal reservoir.
The MAL gene encodes Myelin and Lymphocyte Protein, mainly expressed in T cells with immunomodulatory effects, showing the potential as a target for immunotherapy. However, the mechanism of MAL in ...the regulation of immune infiltration and its association with the prognosis in pan-cancer patients remain elusive. We used the TCGA, TIMER2.0, GTEx, UCSC, and TISCH databases and the R programming tool to explore the role of MAL in cancers. MAL was differently expressed in the majority of malignancies relative to the matched healthy controls. Patients with low MAL levels had adverse survival outcomes in the BRCA and LUAD cohorts. In all cancer types, MAL showed a significant correlation to specific immune-subpopulation abundance in particular T cells as well as B cells. MAL was also implicated in immunological pathways in BRCA and LUAD, suggesting the important role of MAL in cancer immune regulation. In conclusion, the pan-cancer study indicates that MAL with excellent prognostic value is a potential immunotherapy target in multiple cancers.
In a recent study to purify adult T-cell leukemia-lymphoma (ATL) cells from acute-type patients by flow cytometry, three subpopulations were observed in a CD3 versus CD7 plot (H: CD3(high)CD7(high); ...D: CD3(dim)CD7(dim); L: CD3(dim)CD7(low)). The majority of leukemia cells were enriched in the L subpopulation and the same clone was included in the D and L subpopulations, suggesting clonal evolution. In this study, we analyzed patients with indolent-type ATL and human T-cell leukemia virus type I (HTLV-I) asymptomatic carriers (ACs) to see whether the CD3 versus CD7 profile reflected progression in the properties of HTLV-I-infected cells.
Using peripheral blood mononuclear cells from patient samples, we performed multi-color flow cytometry. Cells that underwent fluorescence-activated cell sorting were subjected to molecular analyses, including inverse long PCR.
In the D(%) versus L(%) plot, patient data could largely be categorized into three groups (Group 1: AC; Group 2: smoldering- and chronic-type ATL; and Group 3: acute-type ATL). Some exceptions, however, were noted (e.g., ACs in Group 2). In the follow-up of some patients, clinical disease progression correlated well with the CD3 versus CD7 profile. In clonality analysis, we clearly detected a major clone in the D and L subpopulations in ATL cases and, intriguingly, in some ACs in Group 2.
We propose that the CD3 versus CD7 plot reflects progression of disease stage in patients infected with HTLV-I. The CD3 versus CD7 profile will be a new indicator, along with high proviral load, for HTLV-I ACs in forecasting disease progression.
The morphological discrimination of leukemic from non-leukemic T cells is often difficult in adult T-cell leukemia (ATL) as ATL cells show morphological diversity, with the exception of typical ..."flower cells." Because defects in the expression of CD3 as well as CD7 are common in ATL cells, we applied multi-color flow cytometry to detect a putative leukemia-specific cell population in the peripheral blood from ATL patients. CD4(+) CD14(-) cells subjected to two-color analysis based on a CD3 vs CD7 plot clearly demonstrated the presence of a CD3(dim) CD7(low) subpopulation in each of nine patients with acute-type ATL. The majority of sorted cells from this fraction showed a flower cell-like morphology and carried a high proviral load for the human T-cell leukemia virus type 1 (HTLV-I). Genomic integration site analysis (inverse long-range PCR) and analysis of the T cell receptor Vβ repertoire by flow cytometry indicated that the majority of leukemia cells were included in the CD3(dim) CD7(low) subpopulation. These results suggest that leukemic T cells are specifically enriched in a unique CD3(dim) CD7(low) subpopulation of CD4(+) T cells in acute-type ATL.
The morphological discrimination of leukemic from non‐leukemic T cells is often difficult in adult T‐cell leukemia (ATL) as ATL cells show morphological diversity, with the exception of typical ...“flower cells.” Because defects in the expression of CD3 as well as CD7 are common in ATL cells, we applied multi‐color flow cytometry to detect a putative leukemia‐specific cell population in the peripheral blood from ATL patients. CD4+CD14− cells subjected to two‐color analysis based on a CD3 vs CD7 plot clearly demonstrated the presence of a CD3dimCD7low subpopulation in each of nine patients with acute‐type ATL. The majority of sorted cells from this fraction showed a flower cell‐like morphology and carried a high proviral load for the human T‐cell leukemia virus type 1 (HTLV‐I). Genomic integration site analysis (inverse long‐range PCR) and analysis of the T cell receptor Vβ repertoire by flow cytometry indicated that the majority of leukemia cells were included in the CD3dimCD7low subpopulation. These results suggest that leukemic T cells are specifically enriched in a unique CD3dimCD7low subpopulation of CD4+ T cells in acute‐type ATL. (Cancer Sci 2011; 102: 569–577)
Objectives The aim was to assess the long-term hypertension management in Chinese hypertensive patients who were already treated with valsartan/amlodipine FDC in a real-world observational setting. ...Conclusions Valsartan/amlodipine FDC provided high BP control rate consistently in a one-year real-world registry with high persistence rates and was well tolerated in Chinese hypertensive patients.
Background
Waldenstrom's Macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with immunoglobulin M (IgM) monoclonal ...gammopathy. Bruton's tyrosine kinase (BTK) plays a key role in signaling pathways for the survival of WM clone, particular in patients harboring MYD88 L265P mutations. However, due to target selectivity issue, Clinical uses of early BTK inhibitors are still compromised with off-target activities to many other kinases besides BTK. Orelabrutinib is a novel, highly potent small molecule inhibitor of BTK with superior selectivity for B-cell malignancies and autoimmune diseases. Preliminary efficacy and safety data of ICP-CL-00105 in relapsed/refractory WM patients are presented here.
Methods
ICP-CL-00105 is a single arm, multiple centers, open label, phase 2 study in clinical and histopathological confirmed patients with R/R WM requiring treatment per IWWM-7. MYD88 and CXCR4 mutations were assessed in bone marrow samples at baseline. Orelabrutinib at a daily dose of 150mg was administered orally until disease progression or unacceptable toxicity. Blood samples for IgM were assessed at baseline and every cycle for 6 cycles and every 3 cycles thereafter by central lab. Responses were assessed in accordance with IWWM-6 and NCCN guidelines. The primary endpoint was major response rate (MRR) as assessed by IRC. Key secondary endpoints were MRR as assessed by investigator, overall response rate (ORR), duration of major response (DOMR), progression-free survival (PFS), OS, changes in IgM levels from baseline, improvement on hemoglobin levels and safety. Treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) were assessed according to NCI CTCAE v4.03.
Results
As of June 1, 2021, for the 47 patients the median follow-up duration was 10.5 months. The median age was 63 years (range, 56-68 years), 40 patients (85.1%) were male. 87.2% of patients were at intermediate or high risk according to the Prognostic Scores (IPSS). The proportion of patients with MYD88 L265PCXCR4 wildtype was 83% at baseline. With a median duration of treatment of 9.2 months, MRR was 74.5% as assessed by investigator. ORR was 87.2% with 97.9% patients achieved disease control. The estimated 12-month DOMR were 89.5%. The estimated 12-month PFS and OS were 88.0% and 92.3%, respectively. The median PFS and median OS have not been reached. The MRR was higher in patients with MYD88 L265PCXCR4 wildtype (79.5%). The median IgM level was 30.3g/L at baseline. The decline in the serum IgM levels from baseline were observed with a median reduction by 79.0% (IQR: -89.4, -57.2). The median hemoglobin level at baseline was 102g/L. Durable improvement in hemoglobin levels was found in 83% of patients with a median maximal improvement of 40g/L (IQR: 24.0, 62.0).
Safety data were summarized by the cutoff date of June 1, 2021. The most commonly reported AEs were thrombocytopenia (27.7%)，neutropenia (14.9%), leukopenia (10.6%), upper respiratory infection (14.9%)，weight increased (14.9%), influenza-like disease (12.8%) and rash (10.6%). Most reported AEs (89.5%) were grade 1-2. 16 patients (34.0%) reported grade ≥ 3 TEAE while 9 patients (19.1%) reported grade ≥ 3 TRAE. There was no reported grade ≥3 atrial fibrillation and/or atrial flutter, or grade ≥3 diarrhea. Only One TRAE (2.1%) resulted in drug discontinuation.
Conclusion
Orelabrutinib has demonstrated substantial efficacy in treating r/r WM patients under short-term follow-up. It has shown favorable safety and tolerability profile with limited off-target adverse effects. It has the potential to be a promising treatment option for r/r WM patients.
Hu: Astellas Pharma, Inc.: Research Funding. Tian: Innocare pharma: Current Employment. Zhu: Innocare pharma: Current Employment. Zhang: Innocare pharma: Current Employment. Zhao: Innocare pharma: Current Employment. Zhang: Innocare pharma: Current Employment.
Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease ...(GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (
n
= 23) or ATG-F (
n
= 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (
P
= 0.721) and chronic GVHD (
P
= 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively,
P
= 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (
P
< 0.01) during ATG infusion. There was no difference in the rate of infection between the two treatment groups. There were less adverse effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA-mismatched UR-PBSCT.
Background
For the diagnosis and treatment of adult T‐cell leukemia/lymphoma (ATLL) caused by human T‐lymphotropic virus type 1 (HTLV‐1) are required therapeutic modalities urgently. Non‐human ...primate models for ATLL would provide a valuable information for clinical studies. We did a pilot study to establish an ATLL non‐human primate model using common marmosets (Callithrix jacchus).
Methods
We inoculated HTLV‐1–producing MT‐2 cells into 9‐month‐old marmosets, either intraperitoneally or intravenously. We next administrated MT‐2 cells into 13‐month‐old marmosets under cyclosporine A (CsA) treatment to promote infection. HTLV‐1 infection was determined by measuring HTLV‐1 antibody titer in the common marmosets.
Results
The HTLV‐1 antibody titer increased in the intraperitoneally inoculated marmoset with or without CsA treatment, and it kept over five 5 years though proviral copy number (proviral load, PVL) remained low throughout the study.
Conclusion
We obtained HTLV‐1 asymptomatic carriers of common marmosets by inoculating MT‐2 cells.
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