Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective:To investigate the effect of hematopoietic stem cell transplantationon(HSCT)survival outcomes in older patients with myeloid neoplasms.Methods:We retrospectively analyzed the treatment outcomes of 54 patients aged≥55 years with myeloid neoplasms who underwent HSCT between January 2018 and May 2023 at Zhujiang Hospital of Southern Medical University.Results:Among the 54 pa-tients,45 had acute myeloid leukemia(AML)and 9 had myelodysplastic syndrome.The median age of the patients was 57.5(55-68)years.Fifty-three patients underwent hematopoietic reconstitution,with a median time to neutrophil reconstitution of 13(8-24)days and median time to platelet reconstitution of 15(9-75)days.The cumulative incidence was 23.3%for acute graft-versus-host disease(GVHD)and 24.6%for 3-year chronic GVHD.With a median follow-up of 28.2 months,the 3-year cumulative relapse rate(CIR)was 18%and 3-year non-relapse mortality rate was 28.3%.The 3-year relapse-free survival(RFS)rate was 58.2%and 3-year overall survival(OS)rate was 56.5%.Conclu-sions:HSCT is an effective and safe therapy for achieving long-term survival in older patients with myeloid tumors.

OBJECTIVE: To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. METHODS: A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. RESULTS: 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CONCLUSION CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.
Humans ; Male ; Azoospermia/genetics* ; DNA Copy Number Variations ; Oligospermia/genetics* ; Infertility, Male/genetics* ; Y Chromosome

Objective:To observe and analyze the effect of peripore cavity size on visual function of macular area before and after surgery for idiopathic macular hole (IMH).Methods:A retrospective clinical study. From July 2020 to February 2021, a total of 25 patients with 25 eyes with monocular IMH (operation group) diagnosed by ophthalmology examination in Department of ophthalmology, Fourth Hospital of Hebei Medical University were included in the study. The control group was contralateral healthy eyes. All subjects were examined by best corrected visual acuity (BCVA), microfield of vision, frequency domain optical coherence tomography (SD-OCT), and OCT angiography (OCTA). The diameter of macular hole was measured by SD-OCT. The cystic morphology of deep capillary plexus (DCP) was detected by en face OCT, and the cystic area was measured by Image J software. MP-3 microperimeter was used to measure central macular retinal light sensitivity (MS) and mean macular retinal light sensitivity (MMS). Central macular retinal light sensitivity (CMS), MMS and cystic cavity MS were measured in the operation group. MMS was measured in the control group. The microperimetry images were superimposed on the DCP layer of OCTA to identify and calculate the average MS within the lumen and compare it with the control group. Standard three incisions were performed in all affected eyes by vitrectomy of the flat part of the ciliary body + stripping of the inner boundary membrane + intraocular sterile air filling. Three months after the operation, the same equipment and methods were used to perform relevant examinations. Paired sample t test was used to compare MS between operation group and control group. Pearson correlation analysis was used to analyze the correlation between capsular area, macular hole diameter before and after operation and MS before and after operation. The correlation between BCVA and capsular area before and after surgery was analyzed by Spearman correlation analysis. Results:In the surgical group, the retinal MS was (4.24±3.07) dB. The MMS of control group was (19.08±6.11) dB. The MS in the surgical group was significantly lower than that in the control group, and the difference was statistically significant ( t=10.832, P<0.01). Before operation, the area of cyst was (1.04±0.55) mm 2, and the diameter of macular hole was (564.80±166.59) μm. CMS and MMS were (2.27±2.29) dB and (9.08±3.65) dB, respectively. The diameter of macular hole ( r=0.50, P=0.010) and BCVA before operation ( r=0.57, P<0.001) were positively correlated with peripore cavity area. Before operation, CMS and MMS were negatively correlated with peripore cavity area ( r=-0.53, -0.47; P=0.010, 0.020). At 3 months after surgery, the capsular area was negatively correlated with CMS and MMS ( r=-0.65,-0.76; P=0.020, 0.030). There was no correlation with BCVA ( r=0.23, P=0.470). Conclusions:Retinal MS is decreased in the peri-capsular area of IMH pore. There is a positive correlation between capsule area, BCVA and macular hole diameter before operation. The capsular area is negatively correlated with CMS and MMS before operation.

Objective:To evaluate the correlation between endemic arsenic poisoning and abnormal electrocardiogram (ECG).Methods:PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang data, VIP and other databases were used for literature retrieval, and epidemiological literatures related to abnormal ECG of endemic arsenic poisoning published in domestic and abroad were included in the study. The time limit was from the establishment of the database to December 1, 2020. RevMan 5.3 was used for Meta-analysis of binary variables. Random effect model was selected according to the results of heterogeneity, and odds ratio ( OR) was used as the effect index. Characteristic changes were found by subgroup analysis. Bias was published by funnel plot. Results:Nine articles were included in this Meta-analysis, with 6 articles in Chinese and 3 articles in English, respectively. The abnormal ECG changes included QTc prolongation, ST-T segment change, left axis deviation and arrhythmia. Finally, 1 975 cases were included in the exposure group, including 575 cases of abnormal ECG; 750 cases of control group, including 145 cases of abnormal ECG. Meta-analysis showed that the combined OR value [95% confidence interval ( CI)] of abnormal ECG changes was 4.41 (2.83 - 6.87), with statistical significance between the two groups ( Z = 6.56, P < 0.05); the results of subgroup analysis showed that the combined OR values (95% CI) of QTc prolongation, ST-T segment change, left axis deviation and arrhythmia were 12.30 (5.91 - 25.59), 2.74 (1.39 - 5.41), 2.93 (0.89 - 9.62) and 4.13 (2.38 - 7.17), respectively. Conclusions:Endemic arsenic poisoning may cause abnormal ECG. Prolongation of QTc caused by arsenic exposure may be the characteristic change of abnormal ECG.

Objective:To establish a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method for the direct detection of serum M protein without antibody enrichment, and to assess its detection performance.Methods:Method establishment. A total of 712 waste serum samples were collected from patients who applied for the M protein identification test in Beijing Chaoyang Hospital affiliated to Capital Medical University. The immunoglobulin light chain was obtained by reduction of IgG and IgA by TCEP, and the detection method was preliminarily determined. The waste serum samples from 20 healthy people were collected to determine the range of mass-to-charge ratios of κ and λ light chain ions. 8 parallel tubes and 8 batches were set up for intra-and inter-batch reproducibility evaluation. 10-fold, 100-fold and 200-fold diluted M protein from 23 positive samples were detected by established MALDI-TOF MS method, and its sensitivity was evaluated. 3 methods of IFE, SPE and MALDI-TOF MS were used to detect M protein simultaneously, and the coincidence rate between MALDI-TOF MS and IFE and SPE was calculated.Results:The repeatability within and between batches was 100%, respectively. The original, 10-, 100-and 200-fold dilutions of 23 M protein-positive samples were determined, and the detection limit of MALDI-TOF MS for M protein was 0.06-0.18 g/L. IFE as the gold standard, the overall coincidence rates of SPE and MALDI-TOF MS were 85.9% and 92.3%, respectively, and the positive coincidence rates of SPE and MALDI-TOF MS were 72.8% and 99.7%, respectively, of the 712 samples. Among the different types of M-proteins, MALDI-TOF-MS agreed 100% with IFE M-protein results for IgA, IgD, IgM, free light chain type and biclonal group, while the agreements of SPE for IgM, IgA and free light chain samples were only 66.7%, 58% and 19.5%, respectively. One positive sample in the IgG group was not detected by MALDI-TOF MS. 23 M-proteins positive samples were diluted by original, 10, 100 and 200 times to access the sensitivity of MALDI-TOF MS method. The coincidence rate of MALDI-TOF MS was 100% and IFE was 96% at 10-fold dilution. The coincidence rate of IFE was 28% and 23% of MALDI-TOF MS at 100-fold and 200-fold dilution, respectively.Conclusions:A MALDI-TOF MS method for the detection of serum M-proteins was successfully established. This method has the advantages of high detection throughput, fast speed, good sensitivity, specificity and coincidence rate.

Objective:To explore how to carry out endoscopic skill training in undergraduate medical education and evaluate the teaching effect of modular skill training using endoscopic simulator.Methods:After completing the basic teaching content of the surgical practice course, we added the learning course of the basic theory and basic operation of endoscopy to the students of Clinical Medicine Department from Nantong University. In the experimental group, 292 students were trained by the modular training using the endoscopic simulator. The control group consisted of 114 students, who were treated with ordinary video teaching and instrument operation exercises. After the same class hours of training, the two groups of students were evaluated with intermittent suture and knotting under endoscope as the skill assessment criteria. The chi-square test was performed using SPSS 19.0.Results:The excellent rate and qualified rate of the medical students after the modular training of the endoscopic simulator were 7.5% and 42.8% respectively, which were significantly higher than 0% and 11.4% of the control group, while the unqualified rate of the experimental group was 49.7%, which was also lower than 88.6% of the control group, with significant differences ( P<0.01). Conclusion:Modular training using endoscopic simulator helps the medical undergraduates to quickly increase the ability of endoscopic operation. And in the stage of undergraduate, medical education implementation of the training can shorten the learning curve of endoscopic skills for medical students after they enter clinical practice.

Objective:To investigate the isolation characteristics and the antibiotic resistance of Streptococcus pneumoniae in hospitalized children from the Bao′an District of Shenzhen for many consecutive years, and to provide evidence for the assessment as well as clinical prevention and treatment of Streptococcus pneumoniae infection. Methods:The isolation rate and sample source of Streptococcus pneumoniae isolates as well as age composition of hospitalized children in Bao′an Maternal and Child Health Hospital of Shenzhen city from January 2012 to December 2018 were retrospectively analyzed.The susceptibility of the isolates to antibiotics was tested by disk diffusion method and E-test method. Results:(1) From 2012 to 2018, a total of 90 807 specimens were retrospectively summarized, 9 193 strains of Streptococcus pneumoniae were isolated, with an isolation rate of 10.1%, which was the first pathogen; 98.68% (9 072/9 193 cases) from respiratory tract samples and 97.20% from sputum samples.Among 107 strains isolated from aseptic body fluid specimens, 97 strains were blood specimens. Streptococcus pneumoniae was the most common bacteria with positive culture in aseptic body fluids.(2) The isolation rate of Streptococcus pneumoniae was 10.7% in children under 2 years old, 10.2% in children between 2 and 5 years old and 4.1% in children over 5 years old.About 97% of Streptococcus pneumoniae isolates came from children under 5 years old.(3) According to breakpoints of non-meningitis strains, the sensitivity rate of parenteral Penicillin was 93.18%, the mediation rate was 6.79%, the resistance rate was only 0.03%, the lowest drug concentration to inhibit the growth of 50% bacteria(MIC 50) value was 0.50 and the lowest drug concentration to inhibit the growth of 90% bacteria(MIC 90) value was 2.00; the sensitivity rate of Ceftria-xone was 76.55%, the mediation rate was 20.18%, the resistance rate was 3.26%, the MIC 50 value was 1.00 and the MIC 90 value was 2.00; when interpreted by the breakpoint of meningitis strains, the resistance rate of extra-gastrointestinal Penicillin reached 77.22%, and the mediation rate of Ceftriaxone increased to 30.48% and the drug resistance rate reached 18.45%.The drug resistance rates of Erythromycin, Clindamycin, Tetracycline and Compound neomycin were all over 85.00%.The resistance rates against Levofloxacin and Chloramphenicol were 0.16% and 7.85% respectively.No Vancomycin-resistant Streptococcus pneumoniae was found. Conclusions:Streptococcus pneumoniae is the first bacterial pathogen causing respiratory tract and invasive infection in hospitalized children under 5 years old in this area.Penicillin is still the preferred drug for non-meningitis pneumococcal infection, but the drug resistance rate is high in meningitis patients.

Objective:To investigate the therapeutic effects of noninvasive ventilation on heart failure(HF)after acute myocardial infarction(AMI)in rats.Methods:A rat model of HF after AMI was established by ligation of the left ventricular branch.Thirty male Wistar rats were randomly divided into three groups according to the random number table method: sham operation group, non-treatment group and noninvasive ventilation treatment group(n=30, each group). Echocardiography was performed on the third day after surgery, and parameters including left atrial diameter(LAD), left ventricular end diastolic diameter(LVEDD), interventricular septum thickness(IVS)and left ventricular ejection fraction(LVEF)were recorded.Serum levels of brain natriuretic peptide 45(BNP45), tumor necrosis factor α(TNF-α), matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), and heat-shock protein 70(HSP70)were measured at day 3 after operation by enzyme-linked immunosorbent assays(ELISA). Morphological changes of myocardial tissue were analyzed with hematoxylin-eosin(HE)staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL).Results:Compared with the non-treatment group, LVEDD decreased[(153.9±8.1)mm/m 2vs.(164.7±10.4)mm/m 2, P<0.05]and LVEF increased[(63.9±7.6) % vs. (54.4±9.4) %, P<0.05]in the noninvasive ventilation group .Compared with the non-treatment group, serum levels of BNP45[(0.65±0.07) % vs. (0.73±0.07) μg/L, P<0.05], TNF-α(361.5±13.1) μg/L vs. (399.1±12.6) μg/L( P<0.05), MMP-2(6 892.8±530.2) μg/L vs. (7 406.0±667.5) μg/L( P<0.05)and MMP-9(143.8±5.9) μg/L vs. (151.1±8.3) μg/L( P<0.05)decreased and levels of HSP70[(1.7±0.1)μg/L vs.(1.4±0.1)μg/L, P<0.05]increased in the noninvasive ventilation group.HE staining showed focal accumulation of neutrophils in the epicardium, loss of muscle striation, disorganized cell polarity and enlarged nuclei in the non-treatment group.Meanwhile, alleviated inflammation, scattered neutrophils between cardiomyocytes and misaligned muscle striation were observed in the noninvasive ventilation group.TUNEL results showed that the myocardial apoptotic index was lower in the noninvasive ventilation group than in the non-treatment group( P<0.05). Conclusions:Noninvasive ventilation can effectively improve heart function, reduce inflammatory response and cardiomyocyte apoptosis in rats with AMI-induced HF and may be an effective treatment for HF after AMI.