Towards clinically applicable automated mandibular canal segmentation on CBCT.

OBJECTIVES: To develop a deep learning-based system for precise, robust, and fully automated segmentation of the mandibular canal on cone beam computed tomography (CBCT) images. METHODS: The system was developed on 536 CBCT scans (training set: 376, validation set: 80, testing set: 80) from one center and validated on an external dataset of 89 CBCT scans from 3 centers. Each scan was annotated using a multi-stage annotation method and refined by oral and maxillofacial radiologists. We proposed a three-step strategy for the mandibular canal segmentation: extraction of the region of interest based on 2D U-Net, global segmentation of the mandibular canal, and segmentation refinement based on 3D U-Net. RESULTS: The system consistently achieved accurate mandibular canal segmentation in the internal set (Dice similarity coefficient [DSC], 0.952; intersection over union [IoU], 0.912; average symmetric surface distance [ASSD], 0.046 mm; 95% Hausdorff distance [HD95], 0.325 mm) and the external set (DSC, 0.960; IoU, 0.924; ASSD, 0.040 mm; HD95, 0.288 mm). CONCLUSIONS: These results demonstrated the potential clinical application of this AI system in facilitating clinical workflows related to mandibular canal localization. CLINICAL SIGNIFICANCE: Accurate delineation of the mandibular canal on CBCT images is critical for implant placement, mandibular third molar extraction, and orthognathic surgery. This AI system enables accurate segmentation across different models, which could contribute to more efficient and precise dental automation systems.

[Clinical Analysis of Autologous Peripheral Blood Hematopoietic Stem Cells Mobilization and Collection in Lymphoma Patients].

OBJECTIVE: To analyze the factors influencing collection of autologous peripheral blood hematopoietic stem cells in lymphoma patients. METHODS: Clinical data of 74 patients who received autologous peripheral blood hematopoietic stem cells mobilization and collection in the 940th Hospital of Joint Logistic Support Force of PLA from April 2009 to April 2021 were collected. The effects of gender, age, disease type, stage, course of disease, chemotherapy cycle number, relapse, radiotherapy, disease status and blood routine indexes on the day of collection on peripheral blood hematopoietic stem cell collection were analyzed. RESULTS: The success rate of collection was 95.9%(71/74), and the excellent rate of collection was 71.6%(53/74). There was a significantly statistical differentce in the number of CD34+ cells in grafts collected from patients with chemotherapy cycle ≤6 and >6 ï¼»(9.1±5.2)×106/kg vs (6.4±3.7)×106/kg, P=0.031ï¼½. The number of CD34+ cells in the first collection was positively correlated with WBC count, hemoglobin, platelet count, neutrophil count, lymphocyte count, monocyte count and hematocrit value on the day of collection ( r value was 0.424,0.486,0.306,0.289,0.353,0.428,0.528, respectively). WBC count, hemoglobin, monocyte count and hematocrit value have higher predictive value for the first collection of CD34+ cells. The area under the receiver operating characteristic was 0.7061,0.7845,0.7319,0.7848, respectively. CONCLUSION: Low dose CTX and VP16 chemotherapy combined with G-CSF can effectively mobilize autologous peripheral blood stem cells. The cycle number of chemotherapy relates to the collection of autologous peripheral blood stem cells. After mobilization, the success of the first collection can be better predicted by the blood routine indexes.

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

BACKGROUND: The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). METHODS: In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2 /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2 /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. RESULTS: The median follow-up was 14 months (range 2-36). The primary end point of overall response rate in the intent-to-treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). CONCLUSION: The 5-day 20-mg/m2 /day and 8-day 12-mg/m2 /day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

Diffuse large B­cell lymphoma and monoclonal gammopathy secondary to immune thrombocytopenic purpura: A case report.

The present study reports the case of a patient with diffuse large B-cell lymphoma (DLBCL) and monoclonal gammopathy (MG) secondary to immune thrombocytopenia purpura (ITP). The clinical diagnoses and investigations of this case are reported. To the best of our knowledge, this is the first study to report DLBCL and MG secondary to ITP. The patient presented with a rare constellation of diseases, which made the diagnosis and treatment difficult for the physicians. The patient was followed up for 10 years using the morphological examination of bone marrow cells after chemotherapy, and currently continues with follow-up examinations. Treatments and prognoses for ITP, DLBCL and MG are common. However, treatments and prognoses are unclear for patients with all three conditions. The different clinical manifestations and disease processes of DLBCL and MG secondary to ITP cause difficulties for physicians in terms of treatment and prognosis. The present case report describes the comprehensive evaluation, diagnosis and treatment of a patient with DLBCL and MG secondary to, and concurrent with, ITP.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy.

Lymphoma, which is highly malignant, stems from lymph nodes and lymphoid tissue. Lymphoma cells express programmed death-ligand 1/2 (PD-L1/PD-L2), which binds with programmed cell death 1 protein (PD-1) to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance. Recently, immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors (nivolumab and pembrolizumab) have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients. Accordingly, the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually, which results in an increasing number of patients developing immune-related adverse events (irAEs). The occurrence of irAEs inevitably affects the benefits provided by immunotherapy, particularly when PD-1 inhibitors are applied. However, the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation. This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors. A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Poor pretransplantation minimal residual disease clearance as an independent prognostic risk factor for survival in myelodysplastic syndrome with excess blasts: A multicenter, retrospective cohort study.

BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

Dasatinib for chronic myelomonocytic leukemia with ZMIZ1-ABL1 fusion gene: a case report.

The fusion gene ZMIZ1-ABL1 is rare, with only one known case reported in lymphatic system malignancies, and none reported in a myeloid tumor. Here, we report the case of a patient with chronic myelomonocytic leukemia with the ZMIZ1-ABL1 fusion gene. Elevated leukocytes and splenomegaly were the main manifestations. Remission was achieved with the second-generation tyrosine kinase inhibitor (TKI) dasatinib, and the response has been sustained for 10 months. The treatment results in this case suggest that dasatinib is effective in treating ZMIZ1-ABL1 fusion gene-positive disease.

Healing of the Torn Anterior Horn of Rabbit Medial Meniscus to Bone after Transtibial Pull-Out Repair and Autologous Platelet-Rich Plasma Gel Injection.

OBJECTIVES: The transtibial pull-out repair (TP) is a relatively new method for treating meniscal root tear; however, the clinical evaluation of its healing effect remains controversial. Due to ethical constraints and limitations of imaging techniques in humans, here we dynamically observe the healing effects of TP and TP with platelet-rich plasma gel (PRG) at the histological level using an animal model. METHODS: Platelet-rich plasma (PRP) and PRG of rabbits were prepared. Platelet-derived growth factor (PDGF) and transforming growth factor-ß1 (TGF-ß1) levels in PRP and PRG were determined using an enzyme-linked immunosorbent assay. A rabbit model of anterior horn tear of the medial meniscus and TP surgery were created. PRG was injected between the anterior horn of the medial meniscus and the tibial tunnel. Rabbits were divided into three groups: the anterior horn tear group (Tear group), the anterior horn tear + TP group (TP group), and the anterior horn tear + TP + PRG group (TP + PRG group). The healing effect was observed dynamically using histopathological studies and biomechanical experiments. RESULTS: The platelet content in PRP significantly increased to approximately 4.57 times that of whole blood. PDGF and TGF-ß1 concentrations in PRG increased to 2.46 and 4.15 times those in PRP, respectively. Hematoxylin and eosin (H&E) and Masson staining showed that the number of inflammatory cells in healing tissue decreased and the collagen fibers significantly increased in TP and TP + PRG groups at 4, 8, and 12 weeks postoperatively compared to those in Tear group. Neatly arranged, interlaced, and dense collagen fibers were found between the anterior horn and bone at 12 weeks. H&E and toluidine blue staining showed that the injury to the femoral condyle cartilage was alleviated. The healing performance in TP + PRG group was better and faster than that in TP group. The maximum tensile fracture strength of the meniscus progressively increased at 8 and 12 weeks postoperatively. CONCLUSIONS: Anterior horn injury of the medial meniscus in rabbits can be repaired using the TP technique, and the addition of autologous PRG to the bone tunnel promotes early healing of the meniscus and bone postoperatively. Meanwhile, both treatments can reduce the secondary damage to the cartilage due to osteoarthritis.

[Effects of Thiomersal on Apoptosis and Autophagy of Leukemia Cell Lines].

OBJECTIVE: To investigate the effects of different concentrations of thiomersal on apoptosis and autophagy regulation of human leukemia cell lines U937, CEM-C1 and BALL-1. METHODS: The inhibitory effect of thiomersal on the proliferation of U937, CEM-C1 and BALL-1 cells was detected by CCK-8 assay. Annexin V-FITC/PI double staining flow cytometry was used to detect the apoptosis rate. Western blot was used to detect the effects of thiomersal on autophagy signaling pathway and the expression of PI3K, Akt, mTOR, p-mTOR, caspase-3 and LC3-II proteins. RESULTS: Within 24 and 48 hours, thiomersal inhibited the proliferation of U937, CEM-C1 and BALL-1 cell lines in a time and dose-dependent manner (r24 h=0.295, r24 h=0.452, r24 h=0.103; r48 h=0.821, r48 h=0.665, r48 h=0.821), but no significant time and dose-dependent effect was observed at 72 hours. After 48 hours treatment of thiomersal, the apoptosis rate of U937, CEM-C1 and BALL-1 cells increased in a dose-dependent manner (r=0.819, r=0.763, r=0.835). After 48 hours treatment of thiomersal, the expression levels of PI3K, Akt, mTOR and p-mTOR protein in U937, CEM-C1 and BALL-1 cells decreased in a concentration-dependent manner, the R value of U937 cells was -0.975, -0.899, -0.925 and -0.915, respectively, that of CEM-C1 cells was -0.960, -0.920, -0.861 and -0.927, and that of BALL-1 cells was -0.939, -0.911, -0.896 and -0.926,. which suggested that thiomersal-induced apoptosis of U937, CEM-C1 and BALL-1 cells might be due to the inhibition of PI3K/Akt/mTOR pathway. Thiomersal promoted the apoptosis of U937, CEM-C1 and BALL-1 cells via caspase-3 pathway, and the expressions of caspase-3 and LC3-II were up-regulated in a dose-dependent manner (r=0.976, r=0.914; r=0.976, r=0.986; r=0.961, r=0.974). CONCLUSIONS: Thiomersal can inhibit the proliferation and promote the apoptosis of U937, CEM-C1 and BALL-1 cells. A certain concentration of thiomersal can down-regulate the expression of PI3K/Akt/mTOR pathway related proteins PI3K, Akt, mTOR and p-mTOR in U937, CEM-C1 and BALL-1 cells, and activate autophagy and apoptosis by down-regulation of PI3K/Akt/mTOR pathway.

Long-term follow-up of haploidentical transplantation in relapsed/refractory severe aplastic anemia: a multicenter prospective study.

In recent decades, haploidentical stem cell transplantation (haplo-SCT) to treat severe aplastic anemia (SAA) has achieved remarkable progress. However, long-term results are still lacking. We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy. Long-term outcomes were assessed, mainly focusing on survival and quality of life (QoL). Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children. A total of 287 SAA patients were enrolled, and the median follow-up was 4.56 years (range, 3.01-9.05 years) among surviving patients. During the long-term follow-up, 268 of 275 evaluable patients (97.5%) obtained sustained full donor chimerism, and 93.4% had complete hematopoietic recovery. The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4% ± 2.1% and 84.0% ± 2.2%, respectively. Age (≥18 years) and a poorer performance status (ECOG >1) were identified as risk factors for survival outcomes. For QoL recovery after haplo-SCT, we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance. The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts. At the last follow-up, 74.0% of children and 72.9% of adults returned to normal school or work. These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen (HLA)-matched donors.

Efficacy and safety of pomalidomide and low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma: a multicenter, prospective, single-arm, phase 2 trial.

BACKGROUND: Pomalidomide in combination with dexamethasone has demonstrated positive results in patients with relapsed or refractory multiple myeloma (RRMM), but no data are available in China. We conducted a multicenter, single-arm trial to examine the efficacy and safety of bioequivalent generic pomalidomide plus low-dose dexamethasone in Chinese RRMM patients. METHODS: Adult (≥ 18 years of age) RRMM patients who progressed after at least two previous treatments, including bortezomib and lenalidomide, were eligible. Pomalidomide was given orally at 4 mg/day on days 1 to 21 of a 28-day cycle. Dexamethasone was given at 40 mg/day (either orally or intravenously; 20 mg/day at 75 years or older) on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression or intolerable adverse events (AEs). The primary end point was objective response rate (ORR). RESULTS: Seventy-four patients were enrolled between February 2017 and February 2019. All patients had progressed within 60 days of their last therapy. 74.3% of the patients were resistant to lenalidomide, 31.1% had renal insufficiency and 33.8% had high-risk cytogenetic RRMM. The median follow-up duration was 33.0 months (range 31.1-34.8 months). The ORR was 37.8% in the overall analysis, 32.7% in lenalidomide-refractory patients, 36.0% in patients with high-risk cytogenetics and 34.8% in RRMM patients with renal impairment. The median progression-free survival was 5.7 months (95% CI 3.7-8.8 months). The median overall survival was 24.3 months (95% CI 14.4-41.1 months). The most common grade 3 and 4 treatment-emergent adverse events (TEAEs) were neutropenia (63.5%), leukopenia (37.8%), thrombocytopenia (28.4%), and anemia (31.1%). Pulmonary infection (27.0%) was the most frequent grade 3 and 4 nonhematologic TEAE. No previously unreported AEs were observed. No venous thromboembolism was reported. CONCLUSIONS: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. TRIAL REGISTRATION: The study is registered at Chinese Clinical Trial Registry (ChiCTR) ( ChiCTR-OIC-17013234 , first registered on 03/11/2017).

Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.

Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss-related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, P = 0.731) and HLA loss-related relapse (18.4% vs 20.0%, P = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort [odds ratio (OR): 3.15, P = 0.021] and patients with myeloid malignancies (OR: 3.94, P = 0.021). A higher refined-disease risk index (OR: 6.91, P = 0.033) and donor-recipient ABO incompatibility (OR: 4.58, P = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.

[Research Progress of HO1 on AntiOxidative Stress Injury of MSC --Review].

Mesenchymal stem cell (MSC) is widely used in cell therapy because of its high proliferative and multi directional differentiation potential as well as its low immunogenicity. The transplantation of MSC can help the repair of the injured organs, however, the MSC transplanted to the local organs are affected by oxidative stress and lead to premature aging or apoptosis. Heme oxygenase 1 (HO1) is a key ratelimiting enzyme in the process of heme metabolism, which has the functions of antiinflammation, antioxidation, antiapoptosis, antiaging, reducing cell damage and promoting angiogenesis. Induced high expression of HO1 in MSC could increase the ability of MSC against oxidative stress injury, delay the senescence and apoptosis of MSC, and alleviate cell injury. In this reviews, the research progress of HO1 on antioxidative stress injury of MSC.

Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study.

BACKGROUND: GLS-010 (zimberelimab) is a novel, fully human, anti-programmed death-1 monoclonal antibody that shows promising efficacy and safety in advanced solid tumors. This trial aimed to evaluate the efficacy and safety of GLS-010 (zimberelimab) in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r-cHL). METHODS: This phase II, single-arm, open-label, multicenter clinical trial was conducted at 24 centers in China and enrolled patients with r/r-cHL after two or more lines of therapy. The patients were administered intravenous GLS-010 (zimberelimab) (240 mg, once every 2 weeks) until progression, death, unacceptable toxicity, or consent withdrawal. The primary end-point was the objective response rate assessed by an independent radiology review committee (IRC). This study was registered (NCT03655483). RESULTS: Eighty-five patients were enrolled between August 2018 and August 2019. The median follow-up was 15.8 months. Seventy-seven patients (90.6%; 95% confidence interval [CI] 82.3-95.9) had an IRC-assessed objective response. The complete response rate was 32.9% (n = 28). The 12-month progression-free survival and overall survival rates were 78% (95% CI 67.5-85.6) and 99% (95% CI 91.9-99.8), respectively. Treatment-related adverse events (TRAEs) were observed in 92.9% of participants. Grade III or IV TRAEs occurred in 24 (28.2%) of the 85 participants. The most common grade III or IV TRAEs were abnormal hepatic function (5.9%), hyperuricemia (4.7%), decreased neutrophil count (3.5%), and increased weight (3.5%). Only one grade V AE, gastrointestinal infection, occurred. CONCLUSIONS: GLS-010 (zimberelimab) appears to be effective and safe for the treatment of Chinese patients with r/r-cHL. Long-term follow-up is required to confirm these clinical benefits.

[Application and Research Progress of Lineage Tracing in Differentiation Mechanism of Hematopoietic Stem Cells--Review].

Hematopoietic stem cells (HSCs) reside at the top of the hierarchy and have the ability to differentiate to variety of hematopoietic progenitor cells (HPCs) or mature hematopoietic cells in each system. At present, the procress of HSC and HPC differentiating to the complete hematopoietic system under physiological and stressed conditions is poorly understood. In vivo lineage tracing is a powerful technique that can mark the individual cells and identify the differentiation pathways of their daughter cells, it takes as a strong technical system to research HSC. Traditional lineage tracing studies mainly rely on imaging techniques with fluorescent dyes and nucleic acid analogs. Recently, newly cell tracing technologies have been invented, and the combination of clonal tracing and DNAsequencing technologies have provided a new perspective on cell state, cell fate, and lineage commitment at the single cell level. In this review, these new tracing methods were introduce and discuss, and their advantages over traditional methods in the study of hematopoiesis were summarized briefly.

STAT6 up-regulation amplifies M2 macrophage anti-inflammatory capacity through mesenchymal stem cells.

Extensive infiltration of M2 macrophages plays a crucial role in repairing acute liver failure (ALF), however, the molecular pathways whereby mesenchymal stem cells (MSCs) induce M2 macrophage polarization remains unknown. We investigated the molecular pathways involved in MSC-induced M2 polarization and describe the potential therapeutic effects of M2 macrophages on ALF. The expression of M2 macrophage markers was significantly increased after M0 macrophages were co-cultured with MSCs in vitro. MSCs induced M2 macrophage polarization by activating STAT6, whereas a STAT6 inhibitor significantly inhibited the expression of M2 macrophage polarization markers (IL-4, CD163, TGF-ß, IL-10 and Arg-1). Finally, M2 macrophages significantly reduced the secretion of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from injured hepatocytes. These results demonstrated that MSCs induced M2 macrophage polarization by activating STAT6, and that M2 macrophages increased the expression of anti-inflammatory factors to alleviate ALF.

Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial.

PURPOSE: Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT. PATIENTS AND METHODS: We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m2 of rhG-CSF on days 0-5 and 5 mg/m2 of Dec on days 1-5) or no intervention (non-G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival. RESULTS: The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non-G-Dec group (P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non-G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed. CONCLUSION: Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.

[Fluorescence in Situ Hybridization for Detecting Molecular Cytogenetic Abnormalities of Chronic Lymphocytic Leukemia].

OBJECTIVE: To investigate the value of fluorescence in situ hybridization (FISH) in the diagnosis and prognosis evaluation of patients with chronic lymphocytic leukemia (CLL). METHODS: Ninty-three patients with newly diagnosed CLL were tested by five probes including RB1 (13q14.1), D13S25 (13q14.3), p53(17p13.1), ATM( 11q22.3) and CSP12, while conventional cytogenetics (CC) was used for karyotype analysis. Then the correlation of the molecular cytogenetic abnormalities with the clinical Binet stages, Rai stages and the other related laboratory examinations was analyzed. RESULTS: The detection rate of chromosome abnormality in 93 patients was 79.6%, out of which detection rate of 13q (13q- was the highest and accounted for 45.2%), followed by trisomy 12 (+12) 26.9%, p53 deletion (17p-) 19.4% and ATM deletion (11p-) 17.2%. There were 27 cases (29.0%) with 2 or more abnormalities, including 13 cases with 13q-/17q-, 5 with 13q-/11q-, and 4 with 13q-/+12. Compared with CC test results, the positive rate of FISH detection was significantly higher (χ2=32.127, P＜0.01). There was no significant correlation between FISH results and Rai stages (P＞0.05), meanwhile 17p- highly correlated with later stage of the Binet stages (P=0.012). The molecular cytogenetic abnormalities significantly correlated with age, absolute value of peripheral lymphocyte count and CD38 expression level (P＞0.05). The incidence of 13q- in female (65.4%) was statistically significantly higher than that in male (37.3%) (P=0.015). The unmutated IGHV rate of CLL patients with a 17p- was significantly higher than that in patients without this genetic abnormality (P=0.013). The expression of CD38 was detected among 29.0% of the patients, which significantly correlated with Binet stages (P=0.027) and unmutated IGHV (P=0.006). CONCLUSION: FISH can greatly increase the detection rate of molecular cytogenetic abnormalities in CLL patients, which, as a powerful supplement to the conventional cytogenetics, can be applied for the clinical staging and prognosis evaluation of CLL patients.

Effects of Blast Wave-induced Biomechanical Changes on Lung Injury in Rats.

OBJECTIVE: To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances. METHODS: Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology. RESULTS: Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( P < 0.05 or P < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% vs. 17.8% and 10.0%, P < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups. CONCLUSIONS: The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.