Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Objective:To compare the value of different quantification methods for intraoperative hypotension in predicting postoperative acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The medical records of American Society of Anesthesiologists Physical Status classification Ⅲ-Ⅳ patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective OPCABG, were retrospectively collected at Tianjin Chest Hospital from September 2021 to October 2023. Intraoperative hypotension was quantified using the methods such as the number of occurrence, average decrease in magnitude, duration, and the area under the threshold (mean arterial pressure <65 mmHg, 1 mmHg = 0.133 kPa). Patients were divided into AKI group and non-AKI group based on the occurrence of AKI within 7 days postoperatively. The extended logistic regression model was used to adjust for confounding factors, and the receiver operating characteristic curves were plotted to compare the accuracy of different methods for intraoperative hypotension in predicting postoperative AKI. Results:The results of multivariate logistic regression analysis showed that the frequency of hypotension ( OR=1.03, 95% confidence interval [ CI] 1.01-1.05, P=0.010), duration of hypotension ( OR=1.04, 95% CI 1.01-1.08, P=0.007), and area under the threshold ( OR=1.03, 95% CI 1.01-1.06, P=0.023) were risk factors for postoperative AKI. The areas under the curve for the quantification methods predicting the occurrence of postoperative AKI within 7 days, including the duration of hypotension, area under the threshold, frequency of hypotension, and mean decrease in blood pressure, were 0.751, 0.652, 0.647 and 0.513, respectively. Conclusions:The duration of hypotension, area under the threshold and frequency of hypotension are independent risk factors for postoperative AKI in patients undergoing OPCABG. The duration of hypotension has a higher accuracy in predicting the occurrence of postoperative AKI.

Objective:To compare the value of different quantification methods for intraoperative hypotension in predicting postoperative acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:The medical records of American Society of Anesthesiologists Physical Status classification Ⅲ-Ⅳ patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective OPCABG, were retrospectively collected at Tianjin Chest Hospital from September 2021 to October 2023. Intraoperative hypotension was quantified using the methods such as the number of occurrence, average decrease in magnitude, duration, and the area under the threshold (mean arterial pressure <65 mmHg, 1 mmHg = 0.133 kPa). Patients were divided into AKI group and non-AKI group based on the occurrence of AKI within 7 days postoperatively. The extended logistic regression model was used to adjust for confounding factors, and the receiver operating characteristic curves were plotted to compare the accuracy of different methods for intraoperative hypotension in predicting postoperative AKI. Results:The results of multivariate logistic regression analysis showed that the frequency of hypotension ( OR=1.03, 95% confidence interval [ CI] 1.01-1.05, P=0.010), duration of hypotension ( OR=1.04, 95% CI 1.01-1.08, P=0.007), and area under the threshold ( OR=1.03, 95% CI 1.01-1.06, P=0.023) were risk factors for postoperative AKI. The areas under the curve for the quantification methods predicting the occurrence of postoperative AKI within 7 days, including the duration of hypotension, area under the threshold, frequency of hypotension, and mean decrease in blood pressure, were 0.751, 0.652, 0.647 and 0.513, respectively. Conclusions:The duration of hypotension, area under the threshold and frequency of hypotension are independent risk factors for postoperative AKI in patients undergoing OPCABG. The duration of hypotension has a higher accuracy in predicting the occurrence of postoperative AKI.

Objective:To analyze a novel intronic variant in the SPTB gene and explore its effect on SPTB mRNA splicing.Methods:Clinical data of a child diagnosed with hereditary spherocytosis (HS) and admitted to the First Affiliated Hospital of Xi′an Jiaotong University in February 2022 were analyzed retrospectively. Whole genome sequencing was used to identify disease-causing variantions and the results were validated with Sanger sequencing, mRNA sequencing was used to determine the SPTB gene′s mRNA expression level, and bioinformatics tools were used for splicing site prediction and analysis.Results:The proband is a 2-month-old Han male child, clinically presenting with anemia and jaundice. In the past, jaundice appeared early and was severe during the neonatal period, with significantly elevated indirect bilirubin (203.5 μmol/L), accompanied by moderate anemia. This family consisted of four generations, eight of whom suffered from splenomegaly, jaundice, and anemia. In their peripheral blood, the percentage of microglobular erythrocytes was between 5% and 10%. Under scanning electron microscopy analysis of the proband's father's peripheral red blood cells, about 6% exhibited a mouth-shaped morphology, about 4% were spherical, and about 3% were oval. Following the splenectomy, the father′s anemia and jaundice recovered to normal level. Whole genome sequencing analysis of the proband identified a heterozygous variant in the SPTB gene (NM_ 001355436.2 (SPTB):c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC), which was verified to be co-segregating with the disease in this family line by Sanger sequencing. The results of the SPTB gene mRNA expression level detection showed that the expression levels of the SPTB variant gene were statistically increased in the proband and affected family members (father, grandmother, cousin, second cousin, great-grandmother, great-aunt) (all P<0.05). The SPTB gene′s intron can undergo selective splicing, as demonstrated by analysis using the bioinformatics program ESE Finder. Additionally, predictions from the SpliceAI and SpliceTool software indicated that activation of a new covert splicing donor can result in a code-shift variantion that introduces an early termination codon and nonsense-mediated degradation of the mRNA, which prevents the synthesis of proteins. Conclusion:A new variantion site c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC was found in SPTB gene. This variantion was the pathogenic factor of HS. By affecting the splicing process, this variantion triggers the nonsense mediated mRNA degradation pathway, resulting in inactivation of gene function.

Objective:To understand the influencing factors for cardio-cerebrovascular complications in patients with T2DM and construct a nomogram risk prediction.Methods:The study design was a prospective observational study, and the subjects were selected from hospitalized patients with T2DM admitted to Huangshan City People′s Hospital from May 2022 to April 2023. Data on patients' gender, age, body mass index, alcohol consumption, smoking status, family history of cardio-cerebrovascular diseases, insulin use, duration of diabetes, blood pressure, and routine laboratory test results were collected using the hospital electronic medical record system. At discharge, patients were assessed using the T2DM-Specific Medication Belief Scale (total score range: 10-50), Medication Literacy Assessment Scale (total score range: 0-7), and Morisky Medication Adherence Scale (total score range: 0-8). Patients were followed up by telephone for 6 months after discharge and divided into 2 groups based on the occurrence of cardio-cerebrovascular complications. Logistic regression analysis was performed using SPSS 26.0 software to identify influencing factors for cardio-cerebrovascular complications in T2DM patients. A nomogram prediction model was constructed using R 4.1.0 software, and internal validation of the model was conducted using the Bootstrap method.Results:A total of 294 T2DM patients were included in the analysis. The medication belief score was (32.6±5.6) score, the medication literacy score was (4.2±0.5) score, and the medication adherence score was (6.1±0.8) score. During the 6-month follow-up, a total of 43 patients (14.6%) experienced cardio-cerebrovascular complications, including of coronary heart disease (23 cases), heart failure (12 cases), and stroke (8 cases). Compared to patients without cardio-cerebrovascular complications, patients with complications had higher body mass index, glycosylated hemoglobin A1c (HbA1c), D-dimer, and uric acid levels, as well as lower medication belief scores, medication literacy scores, and medication adherence scores (all P<0.05). Binary logistic regression analysis showed that HbA1c, D-dimer, uric acid, medication belief, medication literacy, and medication adherence were influencing factors for cardio-cerebrovascular complications in T2DM patients. Accordingly, a nomogram prediction model was established. Internal validation results of the model showed that the concordance index was 0.958, the area under the receiver operating characteristic curve was 0.824, and the calibration curve was close to the ideal curve. Conclusions:The current status of medication belief, medication literacy, and medication adherence in T2DM patients was not ideal. High levels of HbA1c, D-dimer, and uric acid, as well as poor medication belief, medication literacy, and medication adherence were risk factors for cardio-cerebrovascular complications in T2DM patients. The nomogram model, which integrated multiple influencing factors, had high value in predicting the risks.

Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Objective:To understand the influencing factors for cardio-cerebrovascular complications in patients with T2DM and construct a nomogram risk prediction.Methods:The study design was a prospective observational study, and the subjects were selected from hospitalized patients with T2DM admitted to Huangshan City People′s Hospital from May 2022 to April 2023. Data on patients' gender, age, body mass index, alcohol consumption, smoking status, family history of cardio-cerebrovascular diseases, insulin use, duration of diabetes, blood pressure, and routine laboratory test results were collected using the hospital electronic medical record system. At discharge, patients were assessed using the T2DM-Specific Medication Belief Scale (total score range: 10-50), Medication Literacy Assessment Scale (total score range: 0-7), and Morisky Medication Adherence Scale (total score range: 0-8). Patients were followed up by telephone for 6 months after discharge and divided into 2 groups based on the occurrence of cardio-cerebrovascular complications. Logistic regression analysis was performed using SPSS 26.0 software to identify influencing factors for cardio-cerebrovascular complications in T2DM patients. A nomogram prediction model was constructed using R 4.1.0 software, and internal validation of the model was conducted using the Bootstrap method.Results:A total of 294 T2DM patients were included in the analysis. The medication belief score was (32.6±5.6) score, the medication literacy score was (4.2±0.5) score, and the medication adherence score was (6.1±0.8) score. During the 6-month follow-up, a total of 43 patients (14.6%) experienced cardio-cerebrovascular complications, including of coronary heart disease (23 cases), heart failure (12 cases), and stroke (8 cases). Compared to patients without cardio-cerebrovascular complications, patients with complications had higher body mass index, glycosylated hemoglobin A1c (HbA1c), D-dimer, and uric acid levels, as well as lower medication belief scores, medication literacy scores, and medication adherence scores (all P<0.05). Binary logistic regression analysis showed that HbA1c, D-dimer, uric acid, medication belief, medication literacy, and medication adherence were influencing factors for cardio-cerebrovascular complications in T2DM patients. Accordingly, a nomogram prediction model was established. Internal validation results of the model showed that the concordance index was 0.958, the area under the receiver operating characteristic curve was 0.824, and the calibration curve was close to the ideal curve. Conclusions:The current status of medication belief, medication literacy, and medication adherence in T2DM patients was not ideal. High levels of HbA1c, D-dimer, and uric acid, as well as poor medication belief, medication literacy, and medication adherence were risk factors for cardio-cerebrovascular complications in T2DM patients. The nomogram model, which integrated multiple influencing factors, had high value in predicting the risks.

Objective:To analyze a novel intronic variant in the SPTB gene and explore its effect on SPTB mRNA splicing.Methods:Clinical data of a child diagnosed with hereditary spherocytosis (HS) and admitted to the First Affiliated Hospital of Xi′an Jiaotong University in February 2022 were analyzed retrospectively. Whole genome sequencing was used to identify disease-causing variantions and the results were validated with Sanger sequencing, mRNA sequencing was used to determine the SPTB gene′s mRNA expression level, and bioinformatics tools were used for splicing site prediction and analysis.Results:The proband is a 2-month-old Han male child, clinically presenting with anemia and jaundice. In the past, jaundice appeared early and was severe during the neonatal period, with significantly elevated indirect bilirubin (203.5 μmol/L), accompanied by moderate anemia. This family consisted of four generations, eight of whom suffered from splenomegaly, jaundice, and anemia. In their peripheral blood, the percentage of microglobular erythrocytes was between 5% and 10%. Under scanning electron microscopy analysis of the proband's father's peripheral red blood cells, about 6% exhibited a mouth-shaped morphology, about 4% were spherical, and about 3% were oval. Following the splenectomy, the father′s anemia and jaundice recovered to normal level. Whole genome sequencing analysis of the proband identified a heterozygous variant in the SPTB gene (NM_ 001355436.2 (SPTB):c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC), which was verified to be co-segregating with the disease in this family line by Sanger sequencing. The results of the SPTB gene mRNA expression level detection showed that the expression levels of the SPTB variant gene were statistically increased in the proband and affected family members (father, grandmother, cousin, second cousin, great-grandmother, great-aunt) (all P<0.05). The SPTB gene′s intron can undergo selective splicing, as demonstrated by analysis using the bioinformatics program ESE Finder. Additionally, predictions from the SpliceAI and SpliceTool software indicated that activation of a new covert splicing donor can result in a code-shift variantion that introduces an early termination codon and nonsense-mediated degradation of the mRNA, which prevents the synthesis of proteins. Conclusion:A new variantion site c.6022+4_6022+18delinsTGGCTCCTCCGTGAAGGGACAGTCCTGC was found in SPTB gene. This variantion was the pathogenic factor of HS. By affecting the splicing process, this variantion triggers the nonsense mediated mRNA degradation pathway, resulting in inactivation of gene function.

Objective:To evaluate the effect of ulinastatin on the postoperative pulmonary complications (PPCs) in the patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:Medical records from patients scheduled for elective OPCABG from September 2021 to August 2023 were retrospectively collected. The patients were divided into ulinastatin and control groups based on the intraoperative use of ulinastatin. Confounding factors were adjusted using propensity score matching and an extended Cox proportional hazards model. The primary outcome was the development of PPCs within 30 days after surgery, and secondary outcomes included length of stay in intensive care unit, length of hospital stay and occurrence of other adverse events.Results:A total of 1 532 patients were included in this cohort study, and 585 cases (38.2%) experienced PPCs. Compared with control group, the incidence of PPCs was significantly decreased (before matching: 42.7% vs. 35.2%, P=0.004; after matching: 42.2% vs. 35.6%, P=0.033), the incidence of acute kidney injury was decreased and no significant differences were found in the length of stay in intensive care unit, length of hospital stay and incidence of other adverse events in ulinastatin group ( P>0.05). In the extended Cox proportional hazard model before and after adjustment for confounding factors, the risk of PPCs was significantly reduced after the use of ulinastatin ( HR value before adjustment was 0.81, 95% confidence interval [ CI] 0.67-0.99, P=0.004; the HR value after adjustment was 0.79, 95% CI 0.65-0.96, P=0.022). The risk of PPCs was significantly decreased in patients aged >65 yr and at high risk of PPCs after using ulinastatin ( HR=0.667, 95% CI 0.542-0.821, P<0.001; hR value was 0.641, 95% CI 0.516-0.812, P<0.001). Conclusions:The intraoperative use of ulinastatin is helpful in decreasing the risk of PPCs in patients undergoing OPCABG.

Objective To explore the effect of UBE2I and FCGR1A gene expressions on the incidence of acquired immune deficiency syndrome(AIDS)combined with active pulmonary tuberculosis(APTB),so as to provide basis for disease monitoring.Methods A total of 98 AIDS patients combined with APTB and 84 AIDS patients combined with latent tuberculosis infection(LTBI)were selected from the validated whole genome transcriptome dataset(GSE37250).The top 30 differentially expressed genes(DEGs)in the two groups of patients were screened.We established the PPI interaction network,transcription factor-differentially expressed gene(TF-DEG),DEG-miRNA,and environmental chemical regulation network of the top 30 DEGs.Receiver operating characteristic(ROC)curves of 11 key DEGs were plotted and Logistic regression analysis was performed.Results There were 6 054 DEGs in the two groups of patients,and UBE2I was an important core node of the PPI interaction network.FCGR1A had the best predictive and indicative ability for AIDS combined with APTB.Univariate Logistic regression showed that high expressions of UBE2I and FCGR1A were risk factors for AIDS combined with APTB(P＜0.05).The regulatory network showed that VEGFB was a key gene in the TF-DEG network,participating in regulation with transcription factors such as SEPT9 and SMAD5.It targeted miRNAs such as hsa-mir-17-5p and hsa-mir-20a-5p,and was affected by environmental chemicals such as valproic acid and copper sulfate.Conclusion VEGFB plays an important role in the pathogenesis of AIDS combined with APTB.The abnormally high expressions of UBE2I and FCGR1A are associated with the disease progression of AIDS combined with APTB.The disease condition can be monitored by detecting the expression level of UBE2I and FCGR1A.