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Paroxysmal kinesigenic dyskinesia (PKD) is a kind of nervous system disease characterized by paroxysmal involuntary movements induced by sudden movements. Neuroimaging studies have found that there are structural changes or abnormal functional connectivity in the basal ganglia, thalamus, cortex and other brain regions in PKD patients. The weakened inhibitory and regulatory function of the basal ganglia to the thalamus or the dysfunction of the thalamus itself may cause over⁃activation of the cortical region, resulting in involuntary movements. Recent studies have found that abnormal cerebellar function plays an important role in the pathogenesis of PKD, and abnormal cerebellar cortex can affect its normal inhibitory effect on deep cerebellar nuclei, also leading to excessive activation of thalamic⁃cortical pathway. This paper reviewed the mechanism and research progress of PKD in recent years, mainly focusing on the basal ganglia⁃thalamic⁃cortical circuit and the cerebellar⁃thalamic⁃cortical circuit, so as to improve clinicians' understanding of the pathogenesis of movement disorders.

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.

Background: HJIG is a potential treatment for erectile dysfunction (ED) that has been used in China for over 20 years. We conducted a multi-center, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of the Chinese Herbal Medicine, Hongjing I granule (HJIG), in patients with mild to moderate erectile dysfunction (ED). Methods: This study is structured as a randomized, double-blind, placebo-controlled trial, executed across multiple centers. The recruitment strategy is primarily oriented towards patients demonstrating a pronounced preference for solely leveraging traditional Chinese medicine (TCM) interventions, a preference that is widely observed within TCM healthcare settings. A total of 100 patients, presenting with mild to moderate ED, specifically linked to the traditional diagnostic criteria of qi deficiency and blood stasis, will be enrolled. These participants will be randomly distributed between the HJIG (N = 50) and placebo (N = 50) arms. The designated treatment period is set at 8 weeks. Primary outcome measures encompass the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, the Sexual Encounter Profile (SEP), and scores derived from the traditional Chinese medicine symptom evaluation. Results: Of the 122 men enrolled, the baseline IIEF-EF score averaged 16.00 [IQR: 13.00, 18.00]. Eight weeks post-randomization, the HJIG group demonstrated a mean change in IIEF-EF scores of 7.80 (±3.25), compared to 3.33 (±3.90) in the placebo group, signifying a marked difference (P < 0.001). The median alterations in SEP3 scores were 0.50 [IQR: 0.36, 0.75] for the HJIG group and 0.50 [0.20, 0.67] for the placebo group, revealing a statistically relevant distinction (P = 0.05). In both primary outcomes, HJIG proved superior to the placebo. Additionally, improvements in TCM symptom scores were notably greater in the HJIG group relative to the placebo, with no adverse events reported across both groups. Conclusion: The Hongjing I granule significantly improved symptoms in patients with mild to moderate ED. However, to validate these findings, further extended randomized trials are warranted. Clinical Trial Registration: The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) and the registration number was ChiCTR2000041127. [ABSTRACT FROM AUTHOR]

Background: Compared to other immune checkpoint molecules, T cell immunoglobulin domain and mucin domain-3 (TIM-3) is highly expressed on natural killer (NK) cells, but its functional role and prognostic significance in acute myeloid leukemia (AML) remains unclear. This study aims to evaluate the role of TIM-3 expression on the cytotoxic and killing capacity of NK cells and its prognostic significance in AML. Methods: AML public single-cell RNA sequencing (scRNAseq) data were used to analyze the correlation of transcript levels between HAVCR2 (encoding TIM-3) and cytotoxic molecules in NK cells. NK cells from the bone marrows of seven newly diagnosed AML patients and five healthy donors (HDs) were stimulated in vitro and cell-killing activity was evaluated. A total of one hundred and five newly diagnosed adult AML patients and seven HDs were tested the expression of TIM-3 and cytotoxic molecules on the bone marrow NK cells by multi-parameter flow cytometry (MFC). Results: Both scRNAseq and MFC analysis demonstrated that TIM-3 expression on NK cells was positively related to the levels of perforin (PFP) and granzyme B (GZMB) (all p < 0.05) in AML. It was PFP and GZMB but not the TIM-3 level that was related to NK-cell-killing activity against K562 cells (p = 0.027, 0.042 and 0.55). A high frequency of TIM-3+ NK cells predicted poorer relapse-free survival (RFS) and event-free survival (EFS) (p = 0.013 and 0.0074), but was not an independent prognostic factor, whereas low GZMB levels in TIM-3+ NK cells independently predicted poorer RFS (p = 0.0032). Conclusions: TIM-3 expression on NK cells is positively related to PFP and GZMB levels but has no relation to cell-killing activity in AML, and low GZMB levels in TIM-3+ NK cells in the diagnostic bone marrows predicts poor outcomes. This study lays a theoretical foundation for the clinical application of immune checkpoint inhibitor treatment. [ABSTRACT FROM AUTHOR]

Background: Relapse was the major cause of treatment failure in patients with myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring. The most used first-line regimens for MRD are immunotherapies. However, for patients who were ineligible for or failed in first-line immunotherapies, options were limited. Methods: A total of 20 patients with myeloid malignancies with recurrent MRD after allo-HSCT were included in this study. The safety and efficacy of venetoclax-based regimens were analyzed. Results: There were 13 patients (65%) treated with venetoclax combined with hypomethylating agents concomitantly and seven patients (35%) treated with venetoclax monotherapy. After venetoclax-based regimens, MRD was eliminated in 11 patients (55%) with 6 subsequently developing recurrent MRD and 5 remaining in molecular remission. MRD declined in two patients (10%), and no responses in seven patients (35%). Among the two patients with declined MRD, one patient finally eliminated MRD after two cycles of the venetoclax-based regimen, and the other patient's MRD further declined after the second regimen. The objective response rate (ORR) was 65%. The median duration of response was 103 (12–313) days. The incidences of grades 3–4 neutropenia, anemia, and thrombocytopenia independently of pretreatment status were 30%, 20% and 20%, respectively. Conclusion: Venetoclax-based regimens are efficient and safe for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT. Plain language summary: What is the context?: Relapse was the major cause of treatment failure in patients with myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring. The most used first-line regimens for MRD are immunotherapies. For patients who were ineligible for or failed in first-line immunotherapies, options were limited. What is new?: A total of 20 patients with myeloid malignancies with recurrent MRD after allo-HSCT were included in this study. The safety and efficacy of venetoclax-based regimens were analyzed. ⮚ Venetoclax-based regimens are efficient for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT. ⮚ After venetoclax-based regimens, MRD was eliminated in 11 patients (55%), and five patients were still MRD eliminated at the time of this writing or until death. ⮚ MRD declined in two patients (10%), and no responses in seven patients (35%). Among the two patients with declined MRD, one patient finally eliminated MRD after two cycles of the venetoclax-based regimen, and the other patient's MRD further declined after the second regimen. ⮚ The objective response rate (ORR) was 65%. ⮚ The median duration of response was 103 (12-313) days. Venetoclax-based regimens are safe for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT. ⮚ The incidences of grades 3–4 neutropenia, anemia, and thrombocytopenia independently of pretreatment status were 30%, 20% and 20%, respectively. What is the impact? This study provides evidence that in the context of preemptive treatment for post-transplant MRD, venetoclax-based regimens may be a choice in patients who were ineligible for or failed in the first-line immunotherapies. [ABSTRACT FROM AUTHOR]

Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch. Here we summarize the evidence for the role of DSA in the development of primary graft failure in haploidentical transplantation and provide consensus recommendations from the European Society for Blood and Marrow Transplant Group on testing, monitoring, and treatment of patients with DSA receiving haploidentical hematopoietic progenitor cell transplantation.