OBJECTIVE: To investigate the clinical efficacy and safety of venetoclax (VEN) in combination with hypomethylating agent (HMA) in the treatment of patients with high-risk myelodysplastic syndromes (MDS). METHODS: A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included. The overall response rate (ORR), modified overall response rate (mORR), overall survival (OS), progression-free survival (PFS), and adverse events of all included patients were evaluated. RESULTS: Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen, 24 cases achieved complete response (CR)/ marrow complete response (mCR), 2 cases achieved partial response (PR), the ORR was 24/30, the median OS was 28.1 months, and the median PFS was 28.1 months. In addition, patients who achieved complete remission / marrow complete remission after treatment had a significantly longer OS than those who did not. Moreover, 12 patients were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). There were grade 3 or higher hematologic adverse events including thrombocytopenia (14 cases), neutropenia (14 cases), febrile neutropenia (10 cases) and anemia (7 cases) as well as gastrointestinal adverse events of any grade, such as vomiting (7 cases), diarrhea (5 cases), and constipation (4 cases). CONCLUSION VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS. This regimen combined with allo-HSCT can improve the prognosis of these patients. Continuous attention to the monitoring and management of adverse events is essential for the patients' safety in this combination therapy.
Humans ; Myelodysplastic Syndromes/drug therapy* ; Sulfonamides/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Female ; Male ; Treatment Outcome ; Middle Aged ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adult

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective To investigate the expression of CD123 in children with acute lymphoblastic leukemia(ALL)and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia(B-ALL).Methods A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology,Children's Hospital of Kunming Medical University,from December 2019 to June 2022.According to the expression of CD123 at initial diagnosis,the children were divided into CD123+group and CD123-group,and the two groups were compared in terms of clinical characteristics and treatment outcome.The factors influencing the prognosis were analyzed.Results Among the 251 children with ALL,there were 146 children(58.2%)in the CD123+group.The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group(P<0.05).Compared with the CD123-group,the CD123+group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years,with a relatively low proportion of children with E2A-PBX1 fusion gene(P<0.05).The multivariate Cox proportional-hazards regression model analysis showed that compared with the>10 years group,the 1-10 years group had a significantly higher overall survival rate(P<0.05),and compared with the high risk group,the moderate risk group had a significantly higher event-free survival rate in children with B-ALL(P<0.05).Conclusions CD123 is widely expressed in children with B-ALL,and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL,which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

Objective:To provide reference for hospital drug selection and clinical rational drug selection,through evaluating the nutritional value of six commonly used balanced compound amino acid injection (BCAA) in clinical practice,including 18AA (250 mL:12.5 g),18AA-I (250 mL:17.5 g),18AA-Ⅱ(250 mL:21.25 g),18AA-IV (250 mL:8.7 g),18AA-V (250 mL:8.06 g),and 18AA-V-SF (250 mL:8.06 g). Methods:Based on the whole egg protein model,the nutritional value of six varieties of BCAA from two aspects were evaluated,including the first limiting amino acid chemical score (CS),value of essential amino acid (EAA) and the comprehensive quality of total EAA (both essential amino acid index and closeness to standard protein). Results:The first limiting amino acid CS value from high to low was 18AA-Ⅱ>18AA>18AA-V=18AA-V-SF>18AA-I=18AA-Ⅳ. Total EAA comprehensive quality:the essential amino acid index from high to low was 18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. The closeness to whole egg protein from high to low was 18AA-Ⅱ=18AA=18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Ultimately,the nutritional value of the 6 varieties of BCAA decreased from high to low:18AA-Ⅱ>18AA>18AA-I>18AA-Ⅳ>18AA-V=18AA-V-SF. Conclusions:Among the six varieties of BCAA,18AA-Ⅱ has the highest nutritional value and the highest amino acid content in the same liquid volume,making it the preferred drug for patients with normal liver and kidney function.

Objective To explore the incidence of long CO VID symptoms in patients infected with Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods According to the inclusion and exclu-sion criteria of literatures,relevant studies without language restrictions published up to 2024 were retrieved from both Chinese and English databases.The Chinese databases were China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP databases,and the foreign databases were PubMed,Embase,and Web of Science.Three-step screening was used to select literatures,and Stata 17.0 software was used for analysis.Results The incidence of at least one sequelae in patients infected with Omicron variant was 29.62％.The most common symptoms included fatigue(19.10％),joint or muscle pain(11.06％),memory loss(9.71％),brain fog(8.80％),cough(8.42％),headache(7.26％),and sore throat(6.68％).Subgroup analysis results showed that with the extension of follow-up(3 months vs 6 months),the incidence of smell or taste changes was significantly re-duced(7.22％vs 0.78％).The higher the proportion of women(＜50％vs 50％-65％vs＞65％),the higher the incidence of joint or muscle pain(1.09％vs 4.62％vs 19.53％);the greater the median age(≥45 years vs＜45 years),the higher the incidence of chest pain or chest distress(0.90％vs 3.86％),all with statistically significant differences(all P＜0.05).Conclusion Incidence of long COVID in Omicron-infected patients is high and can cause various symptoms.Follow-up time,median age and gender proportion have significant impacts on the incidence of some symptoms.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.

Objective: Healthcare workers (HCWs) suffered from a heavy mental health burden during the coronavirus disease-2019 (COVID-19) pandemic. We aimed to explore the differences in sleep disturbance in three waves of the COVID-19 pandemic in Taiwan among HCWs. Moreover, factors associated with sleep disturbances in the third wave were investigated. Methods: This study, with three waves of cross-sectional surveys, recruited first-line and second-line HCWs. The level of sleep disturbance and related demographic variables were collected through self-report questionnaires. Differences in sleep disturbance across the three waves were compared with analysis of variance. Factors associated with the level of sleep disturbance were identified using univariate linear regression and further used for multivariate stepwise and bootstrap linear regression to identify the independent predictors. Results: In total, 711, 560, and 747 HCWs were included in the first, second, and third waves, respectively. For first-line HCWs, sleep disturbance was significantly higher in the third wave than in the first wave. The level of sleep disturbance gradually increased across the three waves for all HCWs. In addition, sleep disturbance was associated with depression, posttraumatic stress disorder (PTSD) symptoms, anxiety about COVID-19, vaccine mistrust, and poorer physical and mental health among first-line HCWs. Among second-line HCWs, sleep disturbance was associated with younger age, depression, PTSD symptoms, lower preference for natural immunity, and poorer physical health. Conclusion The current study identified an increase in sleep disturbance and several predictors among HCWs. Further investigation is warranted to extend the application and generalizability of the current study.