Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Objective:To observe macular vascular density and structural characteristics in children with transfusion-dependent β-thalassemia (TDT).Methods:A retrospective clinical study. From October 2022 to December 2023, 29 TDT children (58 eyes) diagnosed and examined at the Department of Hematology, Affiliated Hospital of Guangdong Medical University were included in the TDT group, along with 29 age- and gender-matched healthy children (58 eyes) as the control group. All participants underwent optical coherence tomography and angiography. Measurements included central macular thickness (CMT), subretinal choroidal thickness (SFCT), choroidal thickness (ChT), choroidal vascularity index, blood flow density in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris layer (CC), and choroidal layer of the macular region, as well as the foveal avascular zone (FAZ) area of the SCP and DCP. A generalized estimating equation was used to compare differences in the above parameters between the two groups. Pearson correlation analysis was employed to examine the relationships between fundus structural parameters, blood flow density, and blood indices.Results:Compared with the control group, the TDT group showed significantly thinner CMT ( χ2=6.044) and ChT at 3.0 mm nasal ( χ2=4.451) and temporal ( χ2=4.767) to the fovea ( P<0.05). The TDT group also demonstrated reduced blood flow density in the inferior DCP ( χ2=5.254), whole CC ( χ2=3.996), and superior CC ( χ2=5.094), as well as enlarged FAZ area in DCP ( χ2=4.286) ( P<0.05). Correlation analysis revealed a negative correlation between SFCT and disease duration ( r=?0.357, P=0.006). Conclusions:In children with TDT, CMT and ChT become thinner and the area of FAZ expands. The blood flow densities of DCP and CC in the macular area decreased.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To observe macular vascular density and structural characteristics in children with transfusion-dependent β-thalassemia (TDT).Methods:A retrospective clinical study. From October 2022 to December 2023, 29 TDT children (58 eyes) diagnosed and examined at the Department of Hematology, Affiliated Hospital of Guangdong Medical University were included in the TDT group, along with 29 age- and gender-matched healthy children (58 eyes) as the control group. All participants underwent optical coherence tomography and angiography. Measurements included central macular thickness (CMT), subretinal choroidal thickness (SFCT), choroidal thickness (ChT), choroidal vascularity index, blood flow density in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris layer (CC), and choroidal layer of the macular region, as well as the foveal avascular zone (FAZ) area of the SCP and DCP. A generalized estimating equation was used to compare differences in the above parameters between the two groups. Pearson correlation analysis was employed to examine the relationships between fundus structural parameters, blood flow density, and blood indices.Results:Compared with the control group, the TDT group showed significantly thinner CMT ( χ2=6.044) and ChT at 3.0 mm nasal ( χ2=4.451) and temporal ( χ2=4.767) to the fovea ( P<0.05). The TDT group also demonstrated reduced blood flow density in the inferior DCP ( χ2=5.254), whole CC ( χ2=3.996), and superior CC ( χ2=5.094), as well as enlarged FAZ area in DCP ( χ2=4.286) ( P<0.05). Correlation analysis revealed a negative correlation between SFCT and disease duration ( r=?0.357, P=0.006). Conclusions:In children with TDT, CMT and ChT become thinner and the area of FAZ expands. The blood flow densities of DCP and CC in the macular area decreased.

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

OBJECTIVE To explore the influence of surgical history on chemotherapy -induced nausea and vomiting （CINV）. METHODS A retrospective case -control study was adopted ，with 824 patients undergoing chemotherapy as the object . A total of 27 items were collected ，including demographic data ，medical history data ，pre-chemotherapy data ，and chemotherapy treatment status. Logistic regression model was used to analyze the relationship between the history of surgery and the risk of CINV . The multiple models were constructed to correct potential confounding factors ，and subgroup analysis was performed on patients with surgical history . RESULTS The incidence of CINV was higher in patients with surgical history . The statistical result before adjustment was [OR＝1.72，95%CI（1.31，2.28），P＜0.001]；after adjusting potential confounding factors ，the statistical result was [OR＝1.78，95% CI（1.28，2.48），P＝0.001]. In the subgroup analysis ，the time between surgery and chemotherapy was different ， and the impact of surgical history on CINV was different ，and the results were statistically significant （P＝0.027）. The risk of CINV showed decreasing trend with the time ，and the results were statistically significant （P for trend ≤0.050）. Compared with patients who had not undergone surgery ，patients who had undergone surgery within one year had a higher risk of CINV [OR＝ 2.33，95%CI（1.52，3.59），P＜0.001]. CONCLUSIONS Patients with surgical history are more prone to CINV ，and the risk of CINV shows a downward trend in the length of time from surgery .

Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.

OBJECTIVE：To explore t he risk factors that may lead to the ineff ectiveness of using palonosetron combined with dexamethasone to prevent chemotherapy-induced nausea and vomiting （CINV），and to provide a reference for the rational choice and use of antiemetic drugs. METHODS ：In a retrospective case-control study ，871 patients who used palonosetron combined with dexamethasone to prevent CINV in a tertiary cancer hospital from 2016 to 2020 were selected as the object. Totally 32 related data such as demographic data ，living habits ，medical history ，examination information and treatment information were counted as variables. Combined with single factor regression ，multi-factor regression， likelihood ratio forward or backward stepwise 163.com regression were used to comprehensively screen the factors for many times. The standard target factors screened by stepwise E-mail：kongtiandong@126.com regression were included in the multivariate Logistic regression analysis，and the regression model was evaluated by the ROC c urve. RESULTS ：The multivariate Logistic regression model fitted well（AUC in ROC was 0.83，but 0.82 after screening ）. The results showed that there were 15 statistically significant independent influential factors ，including 12 independent risk factors ，ie. poor nutritional status （OR＝2.11，95％CI（1.05，4.22），P＝0.036）， history of gastrointestinal disease （OR＝2.76，95％CI（1.87，4.07），P＜0.001），abnormal electrolyte level （OR＝2.54，95％CI （1.74，3.69），P＜0.001），nausea and vomiting 24 h before chemotherapy （OR＝8.47，95％CI（3.28，21.91），P＜0.001），history of chemotherapy-induced vomiting （OR＝3.20，95％ CI （2.18，4.71），P＜0.001），high risk level of vomiting caused by chemotherapy（OR＝3.16，95％CI（2.38，4.20），P＜0.001），application of opioid combined with non-steroidal analgesics （OR＝ 4.18，95％CI（2.06，8.49），P＜0.001），the use of other drugs that stimulate the intestine and stomach （OR＝2.49，95％CI（1.28， 4.83），P＝0.007），history of surgery （OR＝1.88，95％CI（1.34，2.63），P＜0.001），high level of albumin （OR＝1.05，95％CI （1.01，1.08），P＝0.015），multiple days of single chemotherapy （OR＝1.69，95％CI（1.11，2.56），P＝0.014），and opioid analgesia medicine （OR＝1.71，95％CI（1.15，2.53），P＝0.007）；and the following 3 independent protective factors included long time of diagnosis （OR＝0.65，95％CI（0.46，0.93），P＝0.019），non-first chemotherapy （OR＝0.52，95％CI（0.33，0.83），P＝ 0.006），and drugs combined chemotherapy （OR＝0.55，95％CI（0.34，0.90），P＝0.018）. CONCLUSIONS ：Patients with the following conditions are more likely to experience CINV prevention ineffectiveness ，ie. single long-term chemotherapy ，application of chemotherapy plan with a higher risk of emesis ，history of chemotherapy-induced vomiting ，history of gastrointestinal diseases ， nausea and vomiting 24 hours prior to chemotherapy ，history of surgery ，within 1 year of diagnosis ，chemotherapy for the first time，use of opioids ，use of 5-HT3 reuptake inhibitors ，malnutrition and electrolyte disorders.