BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.

Objective To evaluate the application value of golden angle radial sparse parallel(Grasp)sequence in contrast-enhanced MRI of liver.Methods The imaging data of 30 patients who underwent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid contrast-enhanced MRI of liver were collected.With the same equipment,images were collected by Grasp sequence and breath-hold sequence separately,with an interval of less than 3 months.The subjective and objective scores of the late arterial phase and portal venous phase images were evaluated.Results There were no significant differences in all subjective scores of the late arterial phase and portal venous phase images between the two sequences(P＞0.05).The signal-to-noise ratio(SNR)of the late arterial phase images in the Grasp sequence was lower than that in the breath-hold sequence(148.4±52.8 vs 195.6±68.4),and the difference was statistically significant(P＜0.01).Although the SNR of the portal venous phase in the Grasp sequence was lower than that in the breath-hold sequence,the difference was not statistically significant(P＞0.05).There was no statistical difference in the other objective scores between the two sequences(P＞0.05).Conclusion The image quality of Grasp sequence in contrast-enhanced MRI of liver can meet the diagnositic requirements,and it is suitable for patients with poor breath-hold capacity,which has important application value.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective:To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods:A total of 22 813 newborns (12 065 males and 10 748 females) born at the Women's Hospital of Nanjing Medical University from March 18, 2022, to October 31, 2023, were selected. The Dystrophin gene ( DMD) was detected using chip capture next-generation sequencing technology, followed by bioinformatics analysis. Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Serum creatine kinase levels were also tested in suspected male patients. Descriptive analysis was applied for this study. Results:Among the 10 748 girls, 14 carriers of DMD gene were detected (0.013%), of which, nine cases were validated in the family; one case was a de novo mutation, five were inherited from the mother, and three were inherited from the father. The screening identified nine suspected patients among the boys (0.075%), and eight of them were confirmed by family validation, in which three were de novo mutations, and five were inherited from the mother. Among all identified DMD mutations, deletions were the most common one, accounting for 52.2% (12/23), incluling four cases of deletion at 49-51 exon. Conclusions:Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy. According to the preliminary statistics, the incidence rate of DMD/BMD in this area is 1/1 341 male infants and the hotspot mutation is exon 49 to 51 deletion.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular genetic disorder characterized by progressive muscle atrophy, with most patients succumbing to heart or respiratory failure around the age of 20. This article systematically reviews the discovery, pathological research, diagnosis, and development of newborn screening for DMD. Since the 19th century, pioneers such as Bell, Conte, Meryon, Duchenne, and Gowers have laid the foundation for understanding this disease through their discoveries and descriptions of DMD. In the 1980s, molecular biology research further elucidated the pathological mechanisms of DMD and established diagnostic methods. Since the 1970s, newborn screening for DMD has flourished, evolving through various stages including creatine kinase testing, muscle-type creatine kinase isoenzyme testing, and genetic screening. With ongoing research, early screening and diagnostic protocols for DMD have been continuously refined and gradually implemented in clinical practice.

Objective:To observe the efficacy and safety of letermovir in preventing cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Method:From September 2022 to September 2023, retrospective analysis was conducted for the relevant clinical data of 50 recipients of allo-HSCT at First Affiliated Hospital of Zhengzhou University Hospital. Letermovir prophylaxis was offered for preventing cytomegalovirus (CMV) reactivation post-transplantation. They were historically compared with previous patients at the same center without letermovir prophylaxis. The incidence of CMV reactivation, overall survival rate, engraftment status and other adverse events within 100 days post-transplant were compared between two groups. Propensity score matching (PSM) was utilized for controlling confounding factors. Univariate analyses were performed with t and chi-square tests while survival analysis conducted with Kaplan-Meier method.Result:In letermovir group, CMV reactivation was detected in 3 cases (6%) versus 23 cases (46%) in control group. Letermovir significantly reduced the incidence of post-transplant CMV reactivation ( P<0.01). Within Day 100 post-transplant, there was one death in letermovir group with an overall survival rate of 98%. In control group, three deaths occurred with an overall survival rate of 94%. The median survival time of deceased cases was 64 (58-81) day. No statistically significant inter-group difference existed in overall survival rate ( P=0.617). In letermovir group, secondary implantation failure was observed in 3 cases (6%) and it was lower than 12 cases (24%) in control group. Statistically significant inter-group difference existed in secondary implantation failure rate ( P=0.023). However, regarding timing of neutrophil engraftment ( P=0.054) and platelet engraftment ( P=0.649), there were no significant inter-group statistical differences. Hemorrhagic cystitis (HC) occurred in letermovir group (17 cses, 34%) and control group (27cases, 54%). The incidence of HC was significantly lower in letermovir group than that in control group ( P=0.044). However, no statistically significant inter-group difference existed in the incidence of post-transplant EBV infection or acute graft-versus-host disease. Conclusion:Letermovir may significantly lower the incidence of cytomegalovirus (CMV) reactivation after allo-HSCT. It is both effective and safe for preventing CMV disease and improving early outcomes.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.