Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G₁ phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION TPA induces NB4 cell cycle arrest in G₁ phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Humans ; Leukemia, Promyelocytic, Acute ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Cell Division ; Apoptosis ; RNA, Messenger ; Cell Proliferation

Extramedullary plasma cell tumor (EMP) is a kind of plasma cell tumor, and its pathogenesis is not completely clear. According to whether it is independent of myeloma disease, it can be divided into primary and secondary EMP, which have different biological and clinical characteristics. Primary EMP has low invasion, fewer cytogenetic and molecular genetic abnormalities and good prognosis, and surgery and / or radiotherapy are the mainly treatments. Secondary EMP, as the extramedullary invasive progression of multiple myeloma (MM), is often accompanied by high-risk cellular and molecular genetic abnormalities and poor prognosis, chemotherapy, immunotherapy and hematopoietic stem cell transplantation are the mainly treatment. This paper reviews the latest research progress of EMP in the pathogenesis, cytogenetics molecular genetics and treatment, so as to provide reference for clinical work.
Humans ; Plasmacytoma/surgery* ; Prognosis ; Multiple Myeloma/genetics* ; Hematopoietic Stem Cell Transplantation

OBJECTIVE: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876). METHODS: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23). RESULTS: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4⁺CD29⁺ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4⁺CD29⁺ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8⁺CD28^- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8⁺CD28^- T / CD8⁺CD28⁺ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P₃=0.01, P₇=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P₃=0.0351; P₇=0.0142; P₁₄=0.0369). CONCLUSION We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Kinetics ; Myeloid-Derived Suppressor Cells ; Nitriles ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Steroids

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4 CONCLUSION The ITI regimen can raise the ratio of CD4
CD8-Positive T-Lymphocytes ; Humans ; Interferon-alpha ; Interleukin-2 ; Leukemia, Myeloid, Acute/drug therapy* ; Perforin ; Thalidomide

OBJECTIVE: To investigate the efficacy, safety and prognosis of auto-HSCT between classical and modified conditioning regimen in patients with B-cell non-Hodgkin lymphoma. METHODS: 36 patients diagnosed as B-cell non-Hodgkin lymphoma treated with autologous hematopoietic stem cell transplantation from January 2015 to June 2018 in Tianjin Cancer Hospital were retrospectively analyzed. The patients were divided into two groups: Idarubicin group and non-Idarubicin group. The overall survival (OS), progression-free survival (PFS), adverse reactions and hematopoietic reconstitution time between the two groups were compared. Survival analysis was performed by using the Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox regression was used for multivariate analysis. RESULTS: The median follow-up time was 29 months. Among these 36 patients with B-cell non-Hodgkin lymphoma before transplantation, 21 patients achieved CR and 15 patients achieved PR. The reconstitution time of neutrophil (P>0.05) and platelet (P>0.05) was not significantly different between Idarubicin and non-Idarubicin group. Also, the adverse reactions were not significantly different between two groups. The addition of idarubicin showed not aggravate the adverse reactions of patients. The OS and PFS of patients with idarubicin was longer than that of patients without idarubicin. The multivariate analysis showed that, the modified conditioning regimen and the remission state before transplantation were closely associated with prognosis. CONCLUSION The above-mentioned results indicated that the combination of modified conditioning regimen with idarubicin can lengthen the OS and PFS of the patients significantly, and show not aggravate of bone marrow inhibition, moreover, the hematopoietic reconsititution time show not lengthen, which means that it can be a safe and effective choice for autologous HSCT in the patients with B cell non-Hodgkin lymphoma.
Antineoplastic Combined Chemotherapy Protocols ; B-Lymphocytes ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Non-Hodgkin/therapy* ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVE: To investigate the effect and involved mechanism of RSL3 on ferroptosis action in acute leukemia cells MOLM13 and its drug-resistant cells. METHODS: After MOLM13 treated with RSL3, CCK-8 assay was performed to detect cell viability, flow cytometry was used to detect the reactive oxygen species (ROS) level of the cells, RT-qPCR and Western blot were used to detect the expression of glutathione peroxidase 4 (GPX4). After MOLM13/IDA and MOLM13/Ara-C, the drug-resistant cell lines were constructed, the ferroptosis induced by RSL3 was observed. Bone marrow samples were collected from patients with acute monocytic leukemia. RT-qPCR and Western blot were performed to detect the expression of related genes and proteins involved in ferroptosis pathway. RESULTS: RSL3 significantly inhibited the cell viability of MOLM13 and increased the intracellular ROS level, which were partially reversed by ferrostatin-1. The mRNA and protein expression of GPX4 decreased in MOLM13 treated with RSL3. RSL3 inhibited the viability of MOLM13/IDA and MOLM13/Ara-C cells more strongly than that of non-drug resistant cells, also increased the intracellular ROS level . The cytotoxic effects were partially reversed by ferrostatin-1. The mRNA and protein expressions of GPX4 in MOLM13/IDA and MOLM13/Ara-C cells were higher than those in non-drug resistant cells. The mRNA and protein levels of GPX4 in bone marrow of relapsed/refractory acute mononuclear leukemia patients were higher than those of ordinary acute mononuclear leukemia patients. CONCLUSION RSL3 can induce non-drug resistant cells MOLM13 ferroptosis by inhibiting GPX4 activity. MOLM13/IDA and MOLM13/Ara-C are more sensitive to RSL3 compared with non-drug resistant cells MOLM13, which may be caused by the differences in GPX4 expression. The expressions of GPX4 mRNA and protein in relapsed/refractory acute mononuclear leukemia are higher than those in ordinary acute mononuclear leukemia.
Carbolines ; Cell Line ; Child ; Ferroptosis ; Humans ; Leukemia, Myeloid, Acute ; Pharmaceutical Preparations

Objective:To investigate the quality of rehabilitation medical service in tertiary general hospitals in Gansu Province. Methods:Stratified sampling was used to sample tertiary general hospitals in Gansu Province for on-site surveys in 2017. A quality evaluation index system was established in the view of medical service providers, including 17 indicators, based on Donabedian model and experts' opinions. Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) and Rank-sum Ratio were applied to make a comprehensive evaluation on the overall service quality of the hospital rehabilitation medical service. Results:A total of 27 tertiary general hospitals were sampled, in 13 cities/prefectures of Gansu Province. For the structure quality, the compliance rate of the business operation area and the number of beds in the rehabilitation medicine department were 77.78% and 51.85% respectively; while the compliance rates of the physicians, therapists and nurses were all less than 50%. For the process and results quality, the compliance rates were all more than 85%. For the overall quality of rehabilitation medical service, five hospitals were classified as Good, located in Lanzhou, Tianshui and Jiayuguan; 18 hospitals were classified as Medium, located in Longnan, Longdong, Lanzhou and surround, Linxia and Hexi regions; four hospitals classified as Poor, located in Lanzhou and Tianshui. Conclusion:The overall quality of rehabilitation services in the tertiary general hospitals of Gansu Province needs to be improved, and the development of rehabilitation services is uneven in various regions. Comprehensive evaluation provides an important reference to promote the rational distribution of rehabilitation medical resources and improve the quality of rehabilitation medical services.

Qingxin Lianzi Yin （QXLZY）， as an ancient classical formula for clearing the heart and nourishing the Yin， was composed of nine herbs （Scutellariae Radix， Ophiopogonis Radix， Lycii Cortex， Plantaginis Semen， Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma）， coming from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It could clear away the heart-fire， promote the interaction of the heart and kidney， replenish Qi and Yin， and stop strangury-turbidity. It was used to treat gonorrhea of urination， seminal emission， restlessness， wasting-thirst and so on. At present， the usage and dosage of QXLZY and its addition and subtraction are different in clinical practice. Most of the studies just focus on its clinical efficacy， and there is few review literature reflecting its historical evolution. Based on this， this paper systematically clarified the historical evolution， composition， preparation， interpretation， function， and modern clinical application of QXLZY. This work has been explained the historical evolution of QXLZY， and found that it was wildly used in modern clinical， especially suitable for the treatment of chronic urinary system diseases. At the same time， QXLZY also had significant therapeutic effects on neurasthenia， stomatitis， diabetic nephropathy and other aspects. Through the comprehensive analysis of ancient and modern literature， this work explores the true connotation of QXLZY from the perspective of traditional Chinese medicine theory， which can point out the direction of the clinical application and positioning of this famous classical formula after it comes into the market， and also can provide reference basis for its subsequent in-depth research and development.

OBJECTIVE: To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS: The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34 RESULTS: In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.
Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Myelodysplastic Syndromes ; Platelet Transfusion ; Retrospective Studies