Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Cognition ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Monocytes/pathology* ; Polysaccharides/therapeutic use* ; Proteoglycans

Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aβ)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aβ deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Disease Models, Animal ; Humans ; Mice ; Mice, Transgenic

The key technology of the device for the viviperception of the animal mesenteric microcirculation is to simulate the celiac environment in the device. The technical requirements of the device for microcirculation viviperception are that the observation box should be able to "keep warm, preserve moisture, continually perfuse, and fix the sample"; and the lighting should be "intense", "convergence", and "cool". After actual application, it was found that the newly designed and developed the device by research personnel of Wannan Medical College for the viviperception of the animal mesenteric microcirculation can meet the technical requirements, which is able to "keep warm, preserve moisture, continually perfuse, and fix the sample", and using LED lamp as the microscope light source is "intense", "convergence", and "cool". This device is ingenious and reasonable in design, stable in technology, convenient in operation, and competent in microcirculation viviperception. It solves the technical problem to simulate the celiac environment for mesenteric microcirculation viviperception. The device provides convenience to observe and study the microcirculation, which is worth to be applicated widely.

Objective:To explore the predictive value of Red Blood Cell Distribution Width (RDW) in predicting the prognosis of patients with Extracorporeal Membrane Oxygenation (ECMO).Methods:The clinical data of patients undergoing ECMO admitted to Intensive Care Unit of Sichuan Provincial People’s Hospital from January 2015 to January 2020 were retrospectively analyzed. Patients were divided into the survival group and death group according to the prognosis during ICU hospitalization. The patients' basic data , acute physiology and chronic health score system Ⅱ (APACHE Ⅱ), RDW and activated partial thromboplastin time (APTT) at 72 hours after treatment with ECMO were compared between the two groups. Univariate and Logistic regression multivariate analyses were used to analyze the prognostic factors of patients with ECMO, predictive models and death warning scores were established. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficacy of RDW and death warning scores for the prognosis of patients with ECMO.Results:A total of 71 patients with ECMO who met the inclusion criteria were included, including 38 patients in the death group and 33 patients in the survival group. The age, APACHE-Ⅱscore, 72 h RDW and 72 h APTT in the death group were higher than those in the survival group. Respectively, the hospitalization time of ICU in the death group was significantly lower than that in the survival group ( P< 0.05). Logistic regression analysis showed that APACHE-Ⅱscore ( OR=1.117, P=0.047)、72 h RDW( OR=1.102, P=0.029) and 72 h APTT ( OR=1.049, P=0.029) were independent risk factors for death in patients with ECMO. ROC curve analysis showed that the area under ROC curve (AUC) of the APACHE-Ⅱ, score 、72 h RDW and 72 h APTT were 0.691, 0.691 and 0.632( P<0.05), Respectively, the combined AUC was 0.764, the sensitivity was 0.526, and the specificity was 0.909. The death warning score of patients with ECMO was established according to the Predictive model , which is less than 2 points with low risk of death and more than 2 points with high risk of death. The area under the ROC curve of death warning score is 0.8, the sensitivity is 0.607 and the specificity is 0.923. Conclusions:The RDW at 72 hours after treatment with ECMO has a good value in predicting the prognosis of patients with ECMO. Besides, a greater predictive value for the prognosis of patients with ECMO by combining 72 hours RDW, 72 hours APTT with APACHE-Ⅱscore than that of any separate indicator.

Objective:To explore the effect of upregulating CXC-chemokine receptor 7 (CXCR7) in endothelial progenitor cells (EPCs) on angiogenesis after cerebral ischemia-reperfusion injury. Methods:EPCs were isolated and cultured from human umbilical cord blood and identified. Then, the EPCs were transfected with CXCR7 overexpression lentiviral vector, and the expression of CXCR7 was identified with real-time PCR and Western blotting. The tube-like structure formation and apoptosis of EPCs under oxidized low density lipoprotein (ox-LDL) were detected with tube-like structure formation test and Annexin V/PI staining. Cerebral ischemia-reperfusion injury model in rats was established, and the qualified model rats were randomly divided into three groups after 24 hours reperfusion: PBS group (n = 12) was injected with phosphate buffers through tail vein, control group (n = 12) was injected the EPCs infected with control lentiviral vector, and CXCR7 group (n = 12) was injected with EPCs infected with CXCR7 overexpression lentiviral vector. Neurological function scores were determined seven and 14 days after transplantation. The cerebral infarct volume was measured, the number of GFP-positive cells in the ischemic site and the density of capillary were observed. Results:The expression of CXCR7 in EPCs increased after transfection (P < 0.01). Overexpression of CXCR7 improved tube formation and reduced apoptosis of EPCs under ox-LDL (P < 0.05). Compared with PBS and control groups , neurological function improved in CXCR7 group, with less infarct volume, more GFP-positive cells and density of capillary (P < 0.05). Conclusion:Up-regulating CXCR7 can improve the survival and angiogenesis of EPCs, and improve the repair of cerebral ischemia-reperfusion injury.

Clonal Evolution ; Humans ; Multiple Myeloma

Objective: To establish an ion chromatography (IC) method to determine the content of chloride ion and sulfate ion in ethylparaben, and evaluate the quality status of chloride ion and sulfate ion in ethylparaben at different levels.Methods: Ion chromatograph was used.The column was Dionex IonPac AS 18 (250 mm ×4 mm,5 μm) using potassium hydroxide as the mobile phase with gradient elution, the flow rate was 1.0 ml·min-1 , the injection volume was 25 μl, and the quantitative method was standard curve.Results: The method showed good linear relationship within the range of 0.02-4.00 μg·ml-1 for chloride ion (r=0.999 9) and 0.10-10.00μg·ml-1 for sulfate ion (r=0.999 5).The average recovery was 90.12% (RSD=3.4%) and 85.54% (RSD=6.2%) for chloride ion and sulfate ion, respectively (n =9).The content range of chloride ion and sulfate ion was 0.000 3%-0.015 7% and 0.000 9%-0.024 4% in 63 batches of samples, respectively.Conclusion: The established method is simple, fast and accurate, which can be used to determine the contents of chloride ion and sulfate ion in ethylparaben and is helpful to its quality control.