[Epidemic characteristics of mycoplasma pneumoniae infection and drug-resistant gene mutations in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023].

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children's Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher's exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ2=0.021, P=0.885). The positive rates of Mp increased with age (χ2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age (χ2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring (χ2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Characterization of the complete mitochondrial genome sequence of Tracheophilus cymbius (Digenea), the first representative from the family Cyclocoelidae.

Tracheophilus cymbius (Trematoda: Cyclocoelidae) is a common tracheal fluke of waterfowl, causing serious loss in the poultry industry. However, taxonomic identification of T. cymbius remains controversial and confused. Mitochondrial (mt) genomes can provide genetic markers for the identification of closely related species. We determined the mt genome of T. cymbius and reconstructed phylogenies with other trematodes. The T. cymbius mt genome is 13,760 bp in size, and contains 12 protein-coding genes (cox 1-3, nad 1-6, nad 4L, cyt b and atp 6), 22 transfer RNA (tRNA) genes, two ribosomal RNA genes and one non-coding region. All are transcribed in the same direction. The A + T content is 62.82%. ATG and TAG are the most common initiation and termination codons, respectively. Phylogenetic analyses of concatenated nucleotide sequences show T. cymbius grouping in suborder Echinostomata, and clustering together, with high statistical support, as a sister taxon with Echinochasmus japonicus (Echinochasmidae), the two forming a distinct branch rooted to the ancestor of all Echinostomatidae and Fasciolidae species. This is the first report of the T. cymbius mt genome, and the first reported mt genome within the family Cyclocoelidae. These data will provide a significant resource of molecular markers for studying the taxonomy, population genetics and systematics of trematodes.

Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

The complement system activation is involved in the development of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The study aimed to investigate the expression of complement regulatory proteins (CRPs) CD46, CD55 and CD59 in kidneys of 51 AVV patients. The expression of CD46, CD55 and CD59 in kidneys was detected by immunohistochemistry and double immunofluorescence staining. The immunohistochemical examination revealed that expression of the three CRPs could be detected in the glomeruli and tubules of both AAV patients and normal controls. The expression levels of the three CRPs in glomeruli of patients with AAV were significantly lower than those of normal controls. The scores of CD46 and CD55 expression in the tubules of AAV patients were significantly lower than those of normal controls, while there was no significant difference between the scores of CD59 expression in tubules of AAV patients and those of normal controls. Among AAV patients, the expression level of CD46 in glomeruli correlated inversely with the proportion of normal glomeruli, while it correlated with tubular atrophy in renal interstitium (r = -0·305, P = 0·026; r = 0·330, P = 0·023, respectively). The expression levels of CD55 and CD59 in glomeruli correlated with the proportion of total crescents (r = 0·384, P = 0·006; r = 0·351, P = 0·011, respectively). Double immunofluorescence staining indicated that all three CRPs were expressed on endothelial cells, podocytes and mesangial cells in glomeruli. The expression levels of the three CRPs were dysregulated in kidneys of patients with AAV. The expression levels of CD46, CD55 and CD59 were associated with the severity of renal injury of AAV patients.

[Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation treated with sorafenib].

OBJECTIVE: To analyze the efficacy of sorafenib on the treatment of patients diagnosed as acute myeloid leukemia(AML) with FLT3-ITD mutation. METHODS: From January 2012 to February 2015, 42 cases of AML with FLT3-ITD mutation according to MICM (morphology, immunology, cytogenetics and molecular) diagnosis system in our hospital were retrospectively analyzed. Thirty-two cases were refractory to chemotherapy or relapsed, who were treated with sorafenib or combined with chemotherapy. Ten patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were retreated with sorafenib or combined with donor lymphocyte infusion (DLI) or chemotherapy. In the first group, 13 of 32 patients accepted allo-HSCT. RESULTS: The overall response rate of all 42 patients was 73.8%, including 4 (9.5%) complete molecular remission (CMR), 9 (21.4%) complete remission (CR), 8 (19%) complete remission with incomplete hematologic recovery (CRi), 10 (23.8%) partial remission (PR), and 11 (26.2%) none remission (NR). The response rate of sorafenib alone for 17 patients was 70.6%, and that of sorafenib plus chemotherapy was 66.7% (P=0.555). Thirteen patients who received allo-HSCT included 6 CMR/CR/CRi, 4 PR, and 3 NR before transplant. The 2-year overall survival (OS) rate and progress free survival (PFS) rate in all patients were 36.9% and 28.7%, and the corresponding median time were 18 months and 9 months respectively. The 2-year OS rate in 23 patients who received sorafenib combined with allo-HSCT was superior to that in 19 patients not receiving allo-HSCT (45.5% vs 23.9%, P=0.041), so was PFS rate (44.0% vs 9.7%, P=0.014). Twelve cases died of disease progression, four of infection, and one of chronic graft versus host disease after transplant. CONCLUSIONS: Sorafenib combined with chemotherapy improves response rate of AML patients with FLT3-ITD mutation. Those who are treated with sorafenib plus allo-HSCT obtain better long-term survival.

[Effects of subchronic aluminum lactate exposure on learning and memory and transportation of Aß in blood-cerebrospinal fluid in rats].

OBJECTIVE: To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides(Aß) in cerebrospinal fluid in rats. METHODS: A total of 80 male Sprague-Dawley rats were randomly divided into solvent control(distilled water) group and low-, medium-, and high-dose aluminum poisoning groups(10, 30, and 90 mg/kg aluminum lactate), with 20 rats in each group, and the poisoning procedure was performed by gavage for 2 months. The Morris water maze test was used to test the rats' learning and memory, Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1(LRP-1) in rats' choroid plexus, and enzyme-linked immunosorbent assay(ELISA) was used to measure the content of Aß in the cerebrospinal fluid and plasma. RESULTS: The Morris water maze test showed that in the place navigation test, with the increasing training time, the escape latency was significantly shortened in each group and showed significant differences between any two groups(P<0.05). In the spatial probe test, the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43±5.27 s, respectively, which was significantly shorter than that in the control group and the low-dose group(15.81±3.01 s and 13.91±2.17 s)(P<0.05). The numbers of platform crossings in the medium-and high-dose groups were 2.64±1.39 and 1.50±0.76, respectively, which were significantly lower than those in the control group and the low-dose group(4.29±0.914 and 3.56±1.38)(P<0.05). The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aß1-42 in cerebrospinal fluid(320.35±84.82 pg/ml and 327.68±67.51 pg/ml), which was significantly higher than that in the control group(203.46±74.36 pg/ml) (P<0.05). The content of Aß1-42 in plasma showed no significant difference between any two groups(P>0.05), and that of Aß1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups(P>0.05). The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24, P<0.05). CONCLUSION: Subchronic aluminum exposure may reduce learning and memory in rats, and the accumulation of Aß in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus, suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1, influencing the transportation of Aß, and leading to the accumulation of Aß.

[Association between H3K4me3/BDNF and the cognitive function of workers occupationally exposed to aluminum].

Objective: To investigate the influence of occupational aluminum exposure on cognitive function and its relationship with tri-methyl histone H3 lysine residues 4 points (H3K4me3) and brain-derived neurotrophic factor (BDNF) levels. Methods: By cluster random sampling method, a total of 235 cases of male workers selected from a Shanxi aluminum factory were recruited in the study in September 2015. Used the occupational epidemiological investigation questionnaire, which included Mini-Mental State Examination (MMSE) , Clock Drawing Test (CDT) , Digit Span Test (DST, including forward test DSFT and backward test DSBT) , Fuild Object Memory Evaluation (FOME) and Verbal Fluency Test (VFT) , to collect workers' basic information and assess their cognitive function score. Detected the concentration of aluminum in plasma by graphite furnace atomic absorption spectrometry. Workers were divided into three groups by the 25 percentile and 75 percentile of the aluminum content, such as low, middle and high aluminum concentration groups. The concentrations of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay. Results: The levels of aluminum in plasma was 134.36 (100.14, 178.96) µg/L. The scores of MMSE, DSFT, DSBT, DST of high aluminum concentration group were lower than low aluminum group (27.98±1.25 vs 28.83±1.54, 9.19±2.00 vs 10.64±2.87, 6.08±1.63 vs 7.19±3.07, 15.27±3.11 vs 17.81±4.72, all P<0.05) , the scores of CDT, FOME, VFT among three groups had no statistical significance (all P>0.05) . The expression levels of H3K4me3 and BDNF of high aluminum concentration group were lower than the low group [ (18.45±9.81) ng/µg Pro vs (23.76±9.89) ng/µg Pro, (26.07±10.18) ng/ml vs (31.66±9.24) ng/ml, all P<0.05]. Multiple correlation analysis showed that aluminum concentration were negatively correlated toH3K4me3, BDNF, MMSE, DSFT, DST, respectively (r(s)=-0.307、-0.214、-0.252、-0.197, -0.181, all P<0.01) . Conclusion: Exposure to occupational aluminum for a long time may change cognitive function, which go along with the decreasing of H3K4me3 level in lymphocyte and BDNF protein expression in plasma.

[Aluminuminduced impairment in primary cultured rat choroid plexus epithelial cells].

OBJECTIVE: To investigate the impairment in primary cultured rat choroid plexus epithelial cells (CPECs)induced by aluminum. METHODS: The choroid plexus isolated from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin in the sterile area. The obtained single cells were cultured in DMEM with 1% epidermal growth factor and 20% fetal calf serum. Five days later, immunohistochemistry with anti-transthyretin antibody was used to identify the purity of cultured cells. The well-grown cells were treated with aluminum lactate at different concentrations (0, 100, 400, and 1 600 µmol/L for control, lowdose, mediumdose, and highdose groups). Fortyeight hours later, the cell viability, apoptotic rate, level of reactive oxygen species (ROS), and activity of superoxide dismutase (SOD)were measured in each group to evaluate the impairment in primary cultured rat CPECs by aluminum. RESULTS: More than 95% of the cultured cells were identified as CPECs. The medium-and high-dose groups had significantly lower cell viability than the control group(86.74%±4.03% vs 100%, P<0.01; 81.90%±9.17% vs 100%, P<0.01). The high-dose group had significantly lower cell viability than the lowdose group (81.90%±9.17% vs 92.92%±8.81%, P<0.01). The medium-and high-dose groups had significantly higher apoptotic rates than the control group (7.26%±0.99% vs 1.29%±0.03%, P<0.01; 22.25%±1.55% vs 1.29%±0.03%, P<0.01)and the low-dose group (7.26%±0.99% vs 1.68%±0.27%, P<0.01; 22.25%±1.55% vs 1.68%±0.27%, P<0.01). The high-dose group had a significantly higher apoptotic rate than the medium-dose group (22.25%±1.55% vs 7.26%±0.99%, P<0.01). The mediumand high-dose groups had significantly higher fluorescence intensity of ROS than the control group (22.23%±0.41% vs 17.24%±0.09%, P<0.05; 25.10%±1.13% vs 17.24%±0.09%, P<0.05)and the lowdose group (22.23%±0.41% vs 18.31%±0.21%, P<0.05; 25.10%±1.13% vs 18.31%±0.21%, P<0.05). The highdose group had significantly higher fluorescence intensity of ROS than the mediumdose group (25.10%±1.13% vs 22.23%±0.41%, P< 0.05). The low-, medium-and high-dose groups had significantly lower SOD activity than the control group[(28.65±0.74)U/g Hb vs (37.35±1.05)U/g Hb, P<0.05; (22.75±1.94)U/g Hb vs (37.35±1.05)U/g Hb, P<0.05; (13.29±0.64)U/g Hb vs(37.35±1.05)U/g Hb, P<0.05]. The medium-and high-dose groups had significantly lower SOD activity than the low-dose group[(22.75±1.94)U/g Hb vs(28.65±0.74)U/g Hb, P<0.05; (13.29±0.64)U/g Hb vs (28.65±0.74)U/g Hb, P<0.05], while the high-dose group had had significantly lower SOD activity than the medium-dose group[(13.29±0.64)U/g Hb vs (22.75±1.94)U/g Hb, P<0.05]. There were no significant differences in cell viability, apoptotic rate, level of ROS, or activity of SOD between any other two groups (P>0.05). CONCLUSION: Aluminum lactate may induce impairment in primary cultured rat CPECs. It reduces the cell viability, elevates the apoptotic rate, and causes oxidative stress.

[Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia].

Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

[Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation].

Objective: This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD(+) R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods: The clinical data of 26 patients with FLT3-ITD(+) R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results: A total of 26 patients with FLT3-ITD(+) R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95%CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment (P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion: The Gilt-based combination therapy is highly effective in treating FLT3-ITD(+) R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

[Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection].

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Clinical effects of autologous follicular unit extraction transplantation in the treatment of small area secondary cicatricial alopecia after burns].

Objective: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of small area secondary cicatricial alopecia (hereinafter referred to as cicatricial alopecia) after burns. Methods: A retrospective observational study was carried out. According to the adopted treatment methods, 18 patients (12 males and 6 females, aged (29±6) years) who received autologous FUE transplantation for small area cicatricial alopecia after burns from March 2017 to November 2019 in the First Affiliated Hospital of Air Force Medical University were included in FUE transplantation group, and 18 patients (13 males and 5 females, aged (33±5) years) who were treated with expanded flap transplantation for small area cicatricial alopecia after burns by the same surgery team during the same period in the same hospital were included in expanded flap transplantation group. All the patients were followed up for more than 1 year. At the last follow-up, the follicular unit density in the transplanted area was measured by Folliscope hair detection system and the hair survival rate was calculated; the visual analogue scale (VAS) method was adopted to evaluate the treatment effect; patients were asked their satisfaction with the treatment effect and the occurrence of complications during follow-up; the hair growth and the scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area were recorded. Data were statistically analyzed with Fisher's exact probability test and independent sample t test. Results: At the last follow-up, the follicular unit density in the transplanted area of patients in FUE transplantation group was (46.8±2.0)/cm2, which was significantly higher than (42.5±4.3)/cm2 in expanded flap transplantation group (t=3.84, P<0.01); the hair survival rates of patients were similar between the two groups (P>0.05). At the last follow-up, VAS scores evaluating the treatment effect of patients were similar between the two groups (P>0.05); the satisfaction score of patients toward the treatment effect in FUE transplantation group was 8.6±1.1, which was significantly higher than 7.6±0.8 in expanded flap transplantation group (t=2.89, P<0.01). During the follow-up, no inflammation or infection occurred in patients of the two groups, but only 2 patients in expanded flap transplantation group had postoperative pain. At the last follow-up, the transplanted area of patients in the two groups was covered with new hair, and the hair growth direction was basically consistent with the surrounding normal hair; scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area of patients were similar between the two groups (P>0.05). Conclusions: Autologous FUE transplantation has better long-term follicular unit density and patients' satisfaction than expanded flap transplantation in the treatment of small area cicatricial alopecia after burns, showing better postoperative effect and a good prospect of clinical application.

[Clinical analysis of amphotericin B cholesteryl sulfate complex for injection in the treatment of invasive fungal disease for patients with hematological malignancies in 30 cases].

Objective: To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness. Methods: This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives. Results: 30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day. Conclusions: Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.

[Evaluation of the effectiveness of community health education for the prevention and control of retransmission of imported malaria in Zhangjiagang City].

OBJECTIVE: To increase the awareness of malaria prevention and control among people going abroad and returners, so as to prevent the local retransmission of oversea imported malaria. METHODS: Health education interventions for malaria control were given to people going abroad and returners in communities, and the changes of malaria prevention and control knowledge and medical-seeking behaviors were observed among the target populations. RESULTS: There were 367 people going abroad and oversea returners from malaria-endemic areas in Zhangjiagang City from July 2018 to December 2019, and 18 imported malaria cases were found. Following the implementation of community health education, the awareness of malaria prevention and control knowledge increased significantly from 35.09% to 93.08% among the target populations (χ2 = 78.130, P < 0.01), and the proportions of carrying anti-malarial drugs and administration of anti-malarial drugs for emergency treatment increased from 12.14% and 11.46% to 26.79% and 26.79% (χ2 = 8.793 and 9.834, P < 0.05), respectively. In addition, the mean duration from malaria onset to the definitive diagnosis reduced from (5.86 ± 4.45) days to (3.11 ± 1.28) days (U = 64.000, P < 0.05). CONCLUSIONS: Community health education based on the precision community administration is an effective approach for malaria control in current era.

[Analysis of early death factors and prognosis of acute promyelocytic leukemia].

Objective: To summarize the clinical characteristics of an early death in patients with de novo acute promyelocytic leukemia (APL) , analyze the risk factors and direct causes of early death, and perform survival analysis. Methods: The clinical data of 368 patients with de novo APL in three centers (First Affiliated Hospital of Soochow University, Soochow Guangci Hospital, and Soochow Hopes Hospital of Hematology) during January 2011-December 2017 were retrospectively analyzed. The clinical characteristics of patients who suffered hemorrhagic early death and non-hemorrhagic early death were compared. The risk factors for early death, survival, and prognosis of patients with APL were analyzed. Results: Among the 368 de novo APL patients, 31 died early with an early mortality rate of 8.4%. The median time from diagnosis to death was 7 (0-29) d. On comparison of the clinical characteristics of patients with early death and non-early death and subsequent multivariate analysis using a logistic regression model, it was observed that age ≥50 years and WBC ≥10×10(9)/L were independent risk factors for early death (P<0.01) . A total of 27 (87.1%) of the 31 early deaths was directly attributed to hemorrhage as the immediate cause of early death. Hemorrhage was the only cause of death in patients <50 years old and the major cause of death in patients ≥50 years old. A comparison of the clinical characteristics of patients with hemorrhagic early death and patients with non-hemorrhagic early death suggested that the median age and indirect bilirubin concentration of patients with hemorrhagic early death were lower than those with non-hemorrhagic early death (P<0.05) . The median follow-up time for all patients was 41.0 (0.3-101.4) months. The 2-year overall survival (OS) rate was (93.5±1.3) %, and the 5-year OS rate was (91.0±1.5) %. The 2-year disease-free survival (DFS) rate was (98.8±0.6) %, and the 5-year DFS rate was (97.1±0.9) %. The 2-year OS rate of patients ≥50 years old and patients <50 years old was 79.3% vs 94.2%, P=0.000; the 2-year DFS rate was 92.3% vs 98.1%, P=0.023. The respective 2-year OS rates of high-risk and non-high-risk patients were 77.3% and 96.7% (P=0.000) and the respective 2-year DFS rates were 94.0% and 98.4% (P=0.139) . Conclusion: Age and WBC are independent prognostic factors for early death. We observed a difference in early mortality between high-risk and low-risk APL, but no difference in DFS rate.

[CAR T-cell bridging to allo-HSCT for relapsed/refractory B-cell acute lymphoblastic leukemia: the follow-up outcomes].

Objective: This study aims to investigate the efficacy and safety of chimeric antigen receptor (CAR) T-cell bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of recurrent and refractory acute B-lymphocytic leukemia (R/R B-ALL) . Methods: A total of 50 R/R B-ALL patients who underwent CAR T-scell therapy to bridge allo-HSCT in the First Affiliated Hospital of Soochow University from January 2017 to May 2019 were retrospectively analyzed. The overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR) , and transplant-related mortality (TRM) of patients with different bone marrow minimal residual disease (MRD) levels were analyzed before and after CAR T-cell infusion and before allo-HSCT. Results: The response rate of CAR T-cell therapy and the incidence rate of severe cytokine release syndrome were 92% and 28% , respectively. During 55 infusions, no treatment-related deaths occurred in any of the patients. The median time of CAR T-cell infusion to allo-HSCT was 54 (26-232) days, the median follow-up time after CAR T-cell infusion was 637 (117-1097) days, and the 1-year OS and EFS rates were (80.0±5.7) % and (60.0±6.9) % . The 1-year CIR and TRM after allo-HSCT were (28.0±0.4) % and (8.0±0.2) % . After CAR T-cell infusion and before allo-HSCT, patients with bone marrow MRD<0.01% had a significantly longer EFS [ (70.0±7.2) % vs (20.0±12.6) % , P<0.001; (66.7±7.5) % vs (36.4±14.5) % , P=0.008]and lower CIR [ (25.0±0.5) % vs (70.0±2.6) % , P<0.001; (23.08±0.47) % vs (45.45±2.60) % , P=0.038]. Conclusion: CAR T-cell therapy bridging allo-HSCT is safe and effective for recurrent and refractory B-ALL.