Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ2=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Objective:To investigate the efficacy and safety of venetoclax combined with the decitabine, cytarabine, and homoharringtonine (HHT) regimen and donor lymphocyte infusion (DLI) for the preventive and salvage therapy of pediatric acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (HSCT) .Methods:A total of 29 relapsed pediatric/minimal residual disease-positive AML after HSCT were recruited at the Peking University Institute of Hematology from January 1, 2021, to June 1, 2023. They were treated with the above combination regimen and administered with DLI after 24-48 hours at the end of chemotherapy, and the treatment response and adverse reactions were regularly assessed.Results:The overall response rate (ORR) was 75.8%, CR rate was 88.9% (8/9) in the hematologic relapse group, and MRD negativity rate was 61.1% (11/18) in the MRD-positive group. The incidence of agranulocytosis, anemia, and thrombocytopenia with a classification above grade 3 were 100%, 82.7%, and 100%, respectively. The median time of the granulocyte deficiency period was 15 days. Acute graft-versus-host diseases (aGVHD) with a classification of grades Ⅲ-Ⅳ occurred in 11.1% of the patients after DLI, while moderate or severe cGVHD occurred in 7.4% of the patients. The single risk factor for ORR was MNC counts of less than 10×10 8/kg, and the relapse occurred within 100 days. At a median follow-up of 406 days, the 1-year OS was 65%, and the 1-year OS was 57% in the group with no reaction ( P=0.164) compared with 71% in the group who had an overall reaction. Conclusion:The combined regimen based on the DAC, VEN, and modified HA regimen showed a high response rate in the salvage therapy for pediatric AML after the relapse of HSCT. However, bridging to transplantation should be performed immediately after remission to result in a long survival rate.

Objective:To investigate the effects of computerized cognitive remediation therapy (CCRT) combined with social skill training on the improvement of negative symptoms of schizophrenia.Methods:A total of 102 schizophrenic patients who received treatment in Shanxi Province Social Welfare Kangning Psychiatry Hospital from March 2019 to June 2021 were included in this study. They were randomly divided into an intervention group and a control group ( n = 51/group). During the intervention process, because of the reasons such as midway discharge, only 93 patients were included in the final analysis, consisting of 47 patients in the intervention group and 46 patients in the control group. All patients received social skills training. Patients in the intervention group received 8-week CCRT. The Positive and Negative Syndrome Scale and Social Skills Checklist were used to evaluate curative effect in the two groups. Results:After treatment, total score of the Positive and Negative Syndrome Scale and the score of negative symptoms in the intervention group were (46.36 ± 9.33) points and (11.15 ± 3.53) points, respectively, which were significantly lower than (51.06 ± 10.26) points and (16.42 ± 4.75) points in the control group ( t = 2.07, 5.41, both P < 0.05). The total score of Social Skills Checklist, conflict resolution ability score and relationship building ability score in the intervention group were (16.05 ± 6.85) points, (3.36 ± 1.65) points and (3.14 ± 1.83) points, respectively, which were significantly lower than (21.08 ± 8.24) points, (5.92 ± 2.35) points and (6.75 ± 2.51) points, respectively ( t = 2.87, 5.34, 7.00, all P < 0.01). Conclusion:CCRT combined with social skill training can effectively improve the negative symptoms of patients with schizophrenia.

Objective:To construct a risk prediction model for unplanned readmission of patients undergoing cardiac resynchronization therapy (CRT) and verify the performance of the model.Methods:Using convenience sampling, patients who underwent CRT at the Department of Cardiovascular of the First Affiliated Hospital of Zhengzhou University from July 2017 to July 2020 were selected as the modeling group ( n=279) and the internal validation group ( n=120). CRT patients admitted to the Department of Cardiovascular of the First Affiliated Hospital of Zhengzhou University from August 2021 to August 2022 due to the same or related diseases were selected as the external validation group ( n=86). Multivariate Logistic regression was used to explore the influencing factors of unplanned readmission of CRT patients and establish the prediction model. The fitting effect and discrimination of the model were evaluated through the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve. The nomogram was established based on R-4.1.2 and Rstudio software. Results:The multivariate Logistic regression analysis showed that creatinine, left atrial diameter, pulmonary artery systolic pressure, New York Heart Association (NYHA) classification, and body mass index (BMI) were risk factors for unplanned readmission in CRT patients, with statistically significant differences ( P<0.05). The prediction model formula was: P=1/{1+exp[- (0.792×creatinine+1.408×left atrial inner diameter+0.887×pulmonary artery systolic pressure+0.769×NYHA classification-0.970×BMI-2.266) ]}. The area under the ROC curve was 0.874, the maximum value of the Jordan index was 0.636, the optimal threshold was 0.256, the sensitivity was 0.826, and the specificity was 0.810. The accuracy of internal validation and external validation was 90.00% and 90.70%, respectively. Conclusions:The constructed prediction model for unplanned readmission of CRT patients has good predictive performance, and the visualized nomogram improves the practical performance of the model. It helps medical and nursing staff identify high-risk groups of unplanned readmission of CRT patients in the early stage and provides a basis for formulating nursing strategies for different risk groups.

OBJECTIVE: To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. METHODS: Whole exome sequencing was carried out for the proband from the pedigree. Suspected FH gene variants were validated by Sanger sequencing. Clinical manifestation and histopathological examination were used to analyze the pedigree comprehensively. RESULTS: The pedigree met the clinical diagnostic criteria for HLRCC syndrome. The whole exome sequencing showed that the FH gene of the proband had a heterozygous missense variant of c.1490T>C (p.F497S), which was consistent with the Sanger sequencing. The mother, daughter and son of the proband all had the heterozygous missense variant of c.1490T>C (p.F497S). According to the American Society of Medical Genetics and Genomics Classification Standards and Guidelines for Genetic Variations, c.1490T>C (p.F497S) (PM2+PP1-M+PP3+PP4) was a possible pathogenic variant. Based on our literature search, this variant was a new variant that had not been reported. CONCLUSION The FH gene missense variant of c.1490T>C (p.F497S) may be the cause of the HLRCC syndrome pedigree, which provides a basis for the genetic diagnosis and genetic counseling of the HLRCC syndrome.
Carcinoma, Renal Cell/genetics* ; Humans ; Kidney Neoplasms/genetics* ; Leiomyomatosis/pathology* ; Mutation ; Neoplastic Syndromes, Hereditary ; Pedigree ; Phenotype ; Skin Neoplasms ; Uterine Neoplasms

Antigenic purity is important for quality control of the foot-and-mouth (FMD) whole virus inactivated vaccine. The recommended method for evaluation the antigenic purity of FMD vaccine is to check the serum conversion to non-structural protein (NSP) 3AB antibody after 2 to 3 times inoculation of animals with inactivated vaccine. In this study, we developed a quantitative ELISA to detect the amount of residual 3AB in vaccine antigen, to provide a reference to evaluate the antigenic purity of FMD vaccine. Monoclonal antibody (Mab) of NSP 3A and HRP-conjugated Mab of NSP 3B were used to establish a sandwich ELISA to quantify the NSP 3AB in vaccine antigen of FMD. Purified NSP 3AB expressed in Escherichia coli was serially diluted and detected to draw the standard curve. The detectable limit was determined to be the lowest concentration of standard where the ratio of its OD value to OD blank well was not less than 2.0. Results: The OD value was linearly corelated with the concentration of 3AB protein within the range between 4.7 and 600 ng/mL. The correlation coefficient R² is greater than 0.99, and the lowest detectable limit is 4.7 ng/mL. The amount of 3AB protein in non-purified inactivated virus antigen was detected between 9.3 and 200 ng/mL depending on the 12 different virus strains, whereas the amount of 3AB in purified virus antigen was below the lowest detectable limit. The amount of 3AB in 9 batches of commercial FMD vaccine antigens was between 9.0 and 74 ng/mL, whereas it was below the detectable limit in other 24 batches of commercial vaccine antigens. Conclusion: the sandwich ELISA established in this study is specific and sensitive to detect the content of 3AB protein in vaccine antigen of FMD, which will be a useful method for evaluation of the antigenic purity and quality control of FMD inactivated vaccine.
Animals ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus ; Viral Nonstructural Proteins/genetics* ; Viral Vaccines

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

OBJECTIVE: To explore the genetic basis for a child with multiple malformation and growth retardation. METHODS: The child was subjected to low-coverage massively parallel copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technique. RESULTS: G-banding karyotyping analysis has found no abnormality in the boy and his parents. CNV-seq analysis discovered that the child has carried a heterozygous 4.36 Mb deletion (24 020 000-28 380 000) at 7p15.3p15.1. The same deletion was not found in either parent. The deletion has encompassed 28 OMIM genes including HOXA13, CYCS, DFNA5, HOXA11 and HOXA2. Among these, HOXA13 has been associated with distal limb deformity, hypospadias and cryptorchidism. HOXA1, HOXA3 and HOXA4 are involved in the formation of cardiac primordia and primordial tube, and HOXA2 is involved in the development of auditory system. The clinical phenotype of the child was consistent with that of 7p15 deletion syndrome. CONCLUSION Haploinsufficiency of HOXA1, HOXA2, HOXA3, HOXA4 and HOXA13 genes may underlie the clinical phenotype of the child, which is comparable to 7p15 deletion syndrome.

OBJECTIVETo study the risk factor of perioperative complication in gastric cancer patients with radical therapy and its influence on prognosis.

METHODSClinical, pathological and follow-up data of 1 148 gastric cancer patients undergoing radical gastrectomy at Tianjin Medical University Affiliated Tumor Hospital between January 2009 and August 2011 were retrospectively collected. Pearson 2 test and Logistic regression analysis were used to analyze the risk factor of perioperative complication. Cox regression analysis was used to evaluate the influence of perioperative complications on the prognosis in patients after radical gastrectomy. Kaplan-Meier survival curve was applied to calculate the survival.

RESULTSOf 1 148 patients, 851 were male, 297 were female, age ranged from 19 to 89 (average 59.9) years. Perioperative complication occurred in 312 cases (27.2%), including 140 cases of pulmonary infection and 53 cases of abdominal infection. Multivariate Logistic regression analysis showed that ≥65 years old (OR:0.736, 95%CI: 0.558 to 0.971, P=0.030), serum albumin less than 35 g/L(OR:2.626, 95%CI: 1.479 to 4.665, P=0.001), Borrmann type IIII((OR: 0.748, 95%CI: 0.610 to 0.917, P=0.005), tumor site at upper 1/3 of stomach (OR:1.326, 95%CI:1.167 to 1.506, P=0.000), combined organ resection(OR:0.624, 95%CI:0.428 to 0.909, P=0.014) were independent risk factors of perioperative complication. Tumor site at upper 1/3 of stomach (OR:1.649, 95%CI: 1.368 to 1.988, P=0.000), ≥65 years old (OR:0.548, 95%CI:0.379 to 0.792, P=0.001), without intraoperative chemotherapy (OR:1.671, 95%CI:1.146 to 2.437, P=0.008) were independent risk factors of perioperative pulmonary infection; Borrmann type IIII((OR:0.576, 95%CI:0.369 to 0.900, P=0.015), with intraoperative chemotherapy (OR:0.431, 95%CI:0.230 to 0.810, P=0.009), intraoperative blood loss ≥400 ml(OR:0.411, 95%CI:0.176 to 0.959, P=0.040) and combined organ resection (OR:0.412, 95%CI:0.215 to 0.789, P=0.008) were independent risk factors of perioperative intraperitoneal infection. Cox regression analysis revealed that without intraoperative chemotherapy, proximal subtotal or total gastrectomy, TNM stage III(, N3 stage lymph node metastasis, positive soft tissue outside lymph node, combined organ resection and organ failure were independent risk factors affecting the prognosis of gastric cancer patients after radical resection (all P<0.05), however the perioperative complication was not independent risk factor affecting the prognosis (P=0.259). The median survival time was 35 months, and 5-year survival rate was around 38.7%. The median survival time of gastric cancer patients with operative complications and without complications were 28.0 and 36.5 months, and the 5-year survival rates were 37.2% and 39.3%, whose difference was not statistically significant (P=0.259).

CONCLUSIONThere is a higher risk of perioperative complication in those gastric cancer patients with old age, preoperative low serum albumin level, tumor site at upper 1/3 of stomach, Borrmann type IIII(, intraoperative combined organ resection, while the perioperative complication has no significant effects on the long-term survival.