OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To analyze the RHD genotyping and sequencing results of RhD serology negative samples in the clinic, and to further explore the laboratory methods for RhD detection, in order to provide a basis for clinical precision blood transfusion. METHODS: A total of 27 200 whole blood samples were screened for RhD blood group antigen using microcolumn gel card method.Serologic RhD-negative confirmation tests were performed on blood samples that were negative for RhD on initial screening using three different clonal strains of IgG anti-D reagents. The 10 exons of the RHD gene on chromosome 1 were also analyzed by PCR-SSP to determine RHD genotyping.When the PCR-SSP method did not yield definitive results, the RHD gene of the sample was analyzed by the third-generation sequencing. RESULTS: The results of the initial screening test by the microcolumn gel card method showed that 136 of the 27 200 samples were RhD-negative, of which 86 underwent RhD-negative confirmation testing and RHD genotyping, 88.37% (76/86 cases) of the RhD-negative confirmation test results were negative for the three anti-D reagents, and the results of RHD genotyping showed that 67.44% (58/86 cases) of the cases had a complete deletion of 10 exons, and the remaining 28 cases were RHD*711delC (1 case), RHD*D-CE(1-9)-D (1 case), RHD*D-CE(2-9-)D (2 cases), RHD*D-CE(3-9)-D (4 cases), RHD*DEL1 (c.1227G >A) mutation (16 cases), RHD*weak partial 15(845G >A) mutation (3 cases), and a mutation of c.165C >T base was found in 1 sample by three-generation sequencing. CONCLUSION RHD genotype testing of samples that are serologically negative for RhD antigen shows that some of the samples have RHD gene variants, not all of which are total deletions of RHD, suggesting that there are some limitations of the serologic method for RhD detection. Due to the polymorphism of the RHD gene structure, different RhD variants present different serologic features, which need to be further detected in combination with molecular biology testing, especially for the identification of Asian-type DELs, which is important for clinical precision blood transfusion.
Humans ; Rh-Hr Blood-Group System/genetics* ; Genotype ; Polymerase Chain Reaction ; Exons ; Blood Grouping and Crossmatching

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.

Objective:To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia(APL)and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.Methods:Based on the morphological characteristics of APL blast cells,a classification system of 14 categories was established to characterize the inter-and intra-individual cellular morphological heterogeneity of patients.The classification system was used for the morphological analysis of 40 APL patients,and the classification results were statistically analyzed with the patients'conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants.Results:In the FLT3-ITD mutation-positive group,there were significantly fewer cells with regular nuclear shape,hyper granularity,and missing Auer rods(category 1)than in the FLT3 mutation-negative group(P＜0.05).The activated partial thromboplastin(APTT)was significantly longer in the group with regular nucleus compared to the group with irregular nucleus(P＜0.05).In the hypo-granular group,the APTT was also significantly longer compared to the hyper-granular group(P＜0.01),and the proportion of myeloid blast cells was relatively lower(P＜0.05).The peripheral blood white blood cell counts,D-dimer,lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods(-)group than Auer rods increasing group(all P＜0.05).Conclusion:The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells,which helps to better assess the intra-and inter-individual heterogeneity of APL blast cells,and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

Objective:To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model.Methods:A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect.Results:① Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×10 9/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio ( OR) = 3.063, 95% confidence interval (95% CI) was 1.200-7.819], blood purification catheter function ( OR = 4.429, 95% CI was 1.270-15.451), blood flow rate ( OR = 0.928, 95% CI was 0.900-0.957), and frequency of blood pump stops ( OR = 1.339, 95% CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95% CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. ② External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95% CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. Conclusion:The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.