Sepsis-induced coagulopathy(SIC),a critical and potentially lethal condition arising from sepsis,results in endothelial damage and significant coagulation dysregulation,making it a major factor contributing to mortality among sepsis patients.Early diagnosis and treatment of SIC are expected to improve the prognosis of sepsis patients.In 2019,the International Society on Thrombosis and Hemostasis(ISTH)issued the first guidelines for the diagnosis and treatment of SIC,but there are no corresponding protocols in China.Therefore,Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association,and Chinese People's Liberation Army Professional Committee of Critical Care Medicine jointly formulated the"Chinese Expert Consensus on the Diagnosis and Treatment of Sepsis-induced Coagulopathy(2024 edition)."This consensus includes 5 parts:pathogenesis,classification,laboratory approaches,diagnosis and treatment,with a total of 14 evidence-based recommendations to guide clinical practice.

OBJECTIVES: To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis. METHODS: Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed. RESULTS: A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×10⁹/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05). CONCLUSIONS The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.
Child ; Humans ; Male ; Female ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Prognosis ; Genetic Testing ; Mutation ; Hematopoietic Stem Cell Transplantation

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Child ; Female ; Male ; Humans ; High-Throughput Nucleotide Sequencing ; Neoplasm, Residual/genetics* ; Retrospective Studies ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective:To discuss the efficacy of Bushen Huoxue decoction for recovery in patients with intra uterine adhesions （IUA） after trans cervical resection adhesions （TCRA） operation， and to investigate its effect on fibrosis factor. Method:The 110 patients were randomly divided into two groups by random number table （55 cases for control group and 55 cases for observation group）. The patients in both groups got TCRA， and after the operation， they got estradiol valerate tablets+progesterone capsules. The patients in control group additionally got Jinfengwan before meals， 10 g/time， 2 times/day. Patients in observation additionally got syndrome differentiation and treatment by Bushen Huoxuetang， 1 dose/day. The treatment course was 3 months in both groups， and 6 months' follow-up was recorded. Before and after treatment， menstrual volume， period and cycle were recorded. During the follow-up， pregnancy， ectopic pregnancy and abortion were also recorded. Endoscopy and vagina color Doppler ultrasound were conducted to detect endometrial thickness， uterine volume， resistance index （RI）， pulsation index （PI） and blood flow index （FI）. Scores of IUA and syndrome of kidney deficiency and blood stasis were graded. At the 6^th months after treatment， rate of intrauterine re-adhesion was recorded. Levels of transforming growth factor-β₁ （TGF-β₁）， connective tissue growth factor （CTGF）， matrix metalloproteinase inhibitor-1 （TIMP-1）， platelet-derived growth factor （PDGF）， insulin-like growth factor-1 （IGF-1） and matrix metalloproteinase-9 （MMP-9） were detected， and safety was evaluated. Result:Total effective rate of clinical efficacy was 96.36% （53/55） in observation group， higher than 83.64% （46/55） in control group （χ²=4.959， P<0.05）. Recovery rate of menstrual volume， period and cycle were 92.73% （51/55）， 90.91% （50/55）， and 94.55% （52/55） in observation group， higher than 72.73% （40/55）， 76.36% （42/55）， and 76.36% （42/55） in control group（χ²=7.698，χ²=4.245，χ²=7.313，P<0.05， P<0.01）. During the follow-up， rate of intrauterine re-adhesions was 23.64% （13/55） in observation group， lower than 43.64% （24/55） in control group （χ²=4.927，P<0.05）. Pregnancy rate was 45.45% （25/55）， higher than 25.45% （14/55） in control group（χ²=4.807，P<0.05）. Score of syndrome of kidney deficiency and blood stasis and IUA scores in observation group were lower than those in control group （P<0.01）. Endometrial thickness， uterine volume， and FI were higher than those in control group （P<0.01）. Levels of RI， PI， TGF-β₁， CTGF， PDGF， IGF-1 and TIMP-1 were lower than those in control group （P<0.01）， while level of MMP-9 was higher than that in control group （P<0.01）. No adverse reactions related to traditional Chinese medicine were found. Conclusion:Bushen Huoxue decoction can promote the recovery of menstruation， increase the thickness of endometrium， improve the blood circulation of uterus， regulate the expression of fibrogenic factors in vivo， prevent and treat intrauterine adhesions， reduce the rate of intrauterine re-adhesions， and improve the rate of pregnancy， with a good comprehensive effect and high safety for clinical use.

Objective To study the inhibitory effect of T lymphocytes secreting EphrinAl-Caspase-3 in vivo and on the growth of cancer cells in nude mice with breast cancer. Methods Nude mice (n = 35) were inoculated with breast cancer cells to construct a nude mouse model of breast cancer. When the tumor volume reached 0. 1 cm3, 30 nude mice with average size tumor tissue were randomly divided into PBS group, uninfected adenovirus group, T lymphocyte infected with Ad-EphrinAl-Caspase-3 group, and intratumoral transplantation. Tumor size was measured every day 2 to 3. Three groups of tumor-bearing nude mice were selected. After the above-mentioned cell transplantation, the subcutaneous tumor tissue homogenate was obtained every day 2 to 3, and the content of EphrinAl-Caspase-3 was detected by ELISA. At the end of the experiment, the animals in each group were sacrificed by cervical dissection and sliced. The presence of T lymphocytes expressing green fluorescent protein was observed under a fluorescence microscope, and Caspase-3 and Ki-67 were detected by immunofluorescence. Results After one week of inoculation of breast cancer cells into nude mice, the presence of subcutaneous tumors could be touched by hand, which proved that the tumor-bearing animals of breast cancer cells were successfully modeled. On the 8th day after inoculation, the tumor volume of the nude mice in each group became larger, and the difference between the treatment group and the PBS group/T lymphocyte group was extremely significant ( P<0.05). Although the tumor volume of the T lymphocyte transplantation group was slower than that of the PBS control group, there was no statistically significant difference between the two. The expression of EphrinAl-Caspase-3 was detected in the EphrinAl-Caspase-3 treatment group on the 2nd day, reached the peak on the 8th day, and then the secretion decreased gradually. No expression of EphrinAl-Caspase-3 was detected in the PBS control group and the T lymphocyte group. The presence of dispersed green fluorescent protein-labeled EphrinAl-Caspase-3-T lymphocytes was observed in the tumor tissues of the treatment group, while the presence of green fluorescent protein was not detected in the PBS group and the T lymphocyte groups. In the infected cells of the treatment group, the proportion of Caspase-3 positive cells was up- regulated, and the proportion of Ki-67 positive cells was down-regulated. No expression of EphrinAl-Caspase-3 was detected in the PBS group and the T lymphocyte group. Conclusion EphrinAl-Caspase-3 can significantly inhibit the growth of breast cancer cells, thereby exerting an anti-tumor effect.

OBJECTIVE: To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). METHODS: A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. RESULTS: A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P<0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P>0.05). CONCLUSIONS The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.
Child ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Neutropenia ; Polyethylene Glycols ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prospective Studies ; Recombinant Proteins

OBJECTIVE: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1 METHODS: 55 cases of paediatric TCF3-PBX1 RESULTS: Among the 55 children with TCF3-PBX1 CONCLUSION The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.
Adolescent ; Bone Marrow ; Child ; Child, Preschool ; Female ; Humans ; Male ; Neoplasm, Residual ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

Objective: To establish the HPLC fingerprint of wild and cultivated Notholirion bulbuliferum,and recognize them according to the chemical pattern, in the expectation of providing the basis for the quality control and domestication cultivation of N. bulbuliferum of origins. Method: Twenty samples of wild and cultivated N. bulbuliferum collected from different origins were detected by HPLC, and a common mode of fingerprint was established. The Similarity Evaluation System for Chromatographic Fingerprint of TCM (2012A edition) was used to evaluate the similarity of the samples. The differences among the samples were identified by chemical pattern recognition methods, including principal component analysis (PCA),cluster analysis (HCA) and partial least squares discriminate analysis (PLS-DA). Result: The HPLC fingerprint of N. bulbuliferum was obtained,and 26 common peaks were found in the chromatograph. Similarities of all samples were over 0.9,PCA,and HCA and PLS-DA results demonstrated obvious distinctions between wild and cultivated N. bulbuliferum. Eight constituents,such as pcoumaric acid were identified as biomarkers,representing major differences between the two varieties. Conclusion: The HPLC chromatogram of N. bulbuliferum developed in this paper has strong characteristics and repeatability. After being combined with the pattern recognition mode, it can be used as an effective method for evaluating the quality of N. bulbuliferum and distinguishing wild and cultivated N. bulbuliferum,and provide a reference for the quality control and domestication introduction of N. bulbuliferum.

Child ; Correlation of Data ; Flow Cytometry ; Humans ; Immunophenotyping ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis