To achieve non-invasive detection of hemoglobin concentration,a hemoglobin concentration detection method based on support vector regression is designed.A mathematical model for non-invasive hemoglobin detection is established based on the Beer-Lambert law.After removing the noise and baseline drift from the collected photoplethysmography signals,hemoglobin concentration information is extracted,and a recursive feature elimination algorithm is used to select the extracted information and eliminate redundant features.Finally,29 key features are identified as input to construct a hemoglobin prediction model using support vector regression algorithm.Experimental validation is conducted on 249 clinical data samples(199 cases in training dataset and 50 in test dataset),resulting in a root mean square error of 1.83 g/dL between predicted values and references,with a correlation coefficient of 0.75(P<0.01),demonstrating the high consistency of the proposed method and traditional invasive detection methods.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Objective: To analyze blood lead levels of children aged 0-14 in Anqing City during 2015 to 2018, to provide basic data for child poisoning prevention and control. Methods: Using questionnaire surveys, physical examination, and laboratory tests to assess blood lead, age, height, weight, personal habits, environmental factors and other relevant information, to analyze associated factors of elevated blood lead levels. Results: From 2015 to 2018, among the 4 406, 4 177, 3 833 and 3 381 children aged 0-14 in the pediatric outpatient, 662, 326, 225, and 56 cases were found with elevated blood lead levels (EBLLs), with the detection rate of 15.02%, 7.80%, 5.87%, and 1.66%, respectively. Detection rate in boys (16.54%, 7.31%, 6.18% and 1.88%) was similar with that of girls (16.04%, 8.51%, 5.42% and 1.33%) ( χ 2= 2.47 , 2.00, 0.99,1.53, P >0.05). Children in any age groups of 0-14 years might have EBLLs, highest in 14-year-old group in the year of 2015 and 2017. Personal behaviors associated with EBLLs included less meat and dairy products consumption, high frequent exposure to soil dust. In contrast, children who wash their hands before meals and wash toys ≥1 time/week were less likely to suffer from EBLLs ( χ 2=13.58，8.91，7.63，9.22， P <0.05). Environmental factors associated with EBLLs included were less than 50 m between the main road with residency, family members smoke, and parents engaged in construction, welding, automobile maintenance and other industries are more likely to have EBLLs, and the difference is statistically significant ( χ 2=4.92，10.63，22.95， P <0.05). Conclusion The detection rate of EBLLs in Anqing City from 2015 to 2018 depressed by year. Washing hands before meals and cleaning toys frequently could reduce the risk of EBLLs.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Objective: To analyze the clinical characteristics and long-term outcomes with multicenter study for acute lymphoblastic leukemia (ALL) in children over 10 years old and adolescents. Method: Newly diagnosed ALL patients aged from 10 to 18 years old in three hospitals were included in the study from May 1^st 2005 to April 30^th 2015. They were received ALL-2005/2009 protocol following up to December 31^st 2016. The clinical characteristics, outcomes and the prognostic analysis were evaluated between the two protocols. Results: Totally, 237 patients were involved in the study, 76 cases for ALL-2005 and 161 cases for ALL-2009 protocol. Complete remission (CR) after induction therapy was 94.5%. 64 (28.6%) patients relapsed with a median time of 14.5 months and 70 (29.5%) patients passed away during the following time. In long-term follow-up, the 5-year event-free survival (EFS) and 5-year overall survival (OS) of ALL patients were (63.1±3.3)% and (68.4±3.2)%. The 7-year EFS and OS were (61.0±3.5)% and (67.6±3.3)%.The 5-year EFS of intermediate risk group in ALL-2005 and ALL-2009 protocol were (73.6±6.1)% and (71.7±4.3)% with no difference (χ²=0.064, P=0.801). The 5-year EFS of high risk group in two protocols were (27.6±9.6)% and (33.9±9.3)%, showing no significant difference (χ²=0.296, P=0.586). Five years relapsed rate of two protocols were (33.8±5.7)% and (32.6±4.1)% with no difference (χ²=0.055, P=0.815). The mortalities were 36.8% and 29.8% separately (χ²=2.869, P=0.090). Univariate analysis indicated that age, male, risk, BCR/ABL translocation/t(9;22) and resistant to induction were risk prognostic factors in long-term survival (χ²=4.764, 4.796, 46.410, 9.560, 25.450; P=0.029, 0.029, <0.001, 0.049, <0.001). Cox multivariate analysis showed male, risk and resistant to induction were independent risk prognostic factors (RR=1.790, 2.727, 2.719; P=0.021, 0.000, 0.012). Conclusion Protocol ALL-2009 enhanced the chemotherapy intensity in intermediate risk group with no benefit of survival. BCR-ABL fusion or t(9;22) translocation was still the risk factor of prognosis. TKI inhibitor used in these patients could improve survival. EFS rate was increased a little and death rate was decreased in ALL-2009 protocol with no significant lower relapsed rate comparing with ALL-2005 protocol.

Iron deficiency could cause hemoglobin synthesis decrease,and then lead to iron deficiency a-nemia(IDA).The present study has found that incorrect feeding,gastrointestinal disease and deficiency of trace elements are high risks of IDA.Whether febrile seizure is associated with IDA is still controversial.Recent re-search has discovered that infant iron deficiency can lead to poor cognitive inhibitory control,while delayed cord clamping and other measures can effectively prevent IDA in children.Discontinuous complement iron agent can also achieve good effect on treatment.

Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow.The differential diagnosis should always take in account inherited forms of AA,like Fanconi anemia(FA),dyskeratosis-congenita(DC),and Shwachman-Diamond syndrome (SDS).Patient with transfusion-dependent non-severe aplastic anemia(NSAA),with severe AA (SAA) and very severe AA(VSAA),if an human leukocyte antigen (HLA) matched family donor(MFD) is found,then hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) stem cells is the treatment of choice.If a MFD is not available,the immunosuppressive therapy (IST) with the combination of antithymocyte globulin (ATG) plus cyclosporin (CsA) still represents the first line choice.For transfusion-independent NSAA patients,most hematologists suggests no intervention,however,some studies indicate the patients with transfusion-independent NSAA may benefit from IST,and the rate of progression to SAA and transfusion-dependent NSAA is lower than other observation groups.So a multicenter randomized clinical trial is needed.

OBJECTIVETo study the role of Th17/Treg imbalance in the immune pathogenesis and therapeutic significance in childhood aplastic anemia (AA).

METHODWe analyzed data from 43 children (male: female = 14: 29) with AA, all the cases were at the age of 2 to 14 years at diagnosis, and were hospitalized at our department of pediatrics between January 2012 and October 2013 in the Second Hospital of Anhui Medical University. All these patients were divided into 2 groups, severe AA (SAA) group (n = 25, male: female = 8: 17, 2-14 years old) and non-severe AA (NSAA) group (n = 18, male: female = 6: 12, 2-14 years old), depending on the severity at first diagnosis. As to the treatment, we analyzed data at 3 phases of treatment, diagnosis (n = 43, male: female = 14: 29, 2-14 years old), transfusion-indenpendence (n = 8, male: female = 5: 3, 2-11 years old), complete response (n = 6, male: female = 3: 3, 2-11 years old); at the same time, AA children who did not respond to the treatments were considered as failed treatment control (transfusion-indenpendence with failed treatment group, n = 5, male: female = 1: 4, 3-8 years old; complete response failed treatment group, n = 4, male: female = 2: 2, 4-11 years old). The ratio of Treg and Th17 cells in CD4(+) T cells were tested by flow cytometry. The levels of IL-6 and IL-17 in plasma were determined by ELISA. During the same period, 25 age-matched healthy children (male: female = 12: 13, 3-14 years old) were recruited as normal control, 9 cases (male: female = 5: 3, 2-11 years old) of AA children induced by chemotherapy as diagnosis control group. Differences in variables were analyzed using ANOVA and t-tests or the Kruskal-Wallis and Mann-Whitney U-tests, as appropriate. Correlation analysis was evaluated by the Spearman rank correlation test.

RESULT(1) The ratio of Th17 cells in newly diagnosed AA patients were higher than that of normal group or diagnosis control group [1.63% (1.27%, 2.48%) vs. 0.4% (0.35%, 0.51%) or 0.50% (0.45%, 0.75%), both P < 0.01] while the ratio of Treg cells was lower [4.24% (3.10%, 5.29%) vs. 7.03% (6.56%, 7.48%) or 7.50% (6.60%, 8.30%), both P < 0.01] and the proportion of Th17/Treg were significantly higher [0.53(0.34, 0.69) vs. 0.06 (0.05, 0.07) or 0.09 (0.08,0.11), both P < 0.01]. (2) The levels of IL-6 and IL-17 in newly diagnosed AA patients were higher than in normal group [ (223 ± 92) vs. (116 ± 18) ng/L, (26.2 ± 12.0) ng/L vs. (10.6 ± 2.1) ng/L, P both < 0.01]. There was a positive correlation between Th17 cells and some Th17 cells related cytokines such as IL-17 and IL-6 (r = 0.62, 0.64, P both < 0.01). (3) The ratio of Th17, Th17/Treg, and the levels of IL-6 and IL-17 in children with SAA were also higher than in normal group [1.80% (1.25%, 2.61%) vs. 0.40% (0.35%, 0.51%), 0.57% (5.10%,0.82%) vs. 0.06% (0.05%, 0.07%), (225 ± 108) vs. (116 ± 18) ng/L, (25.9 ± 12.6) vs. (10.6 ± 2.1)ng/L, all P < 0.01]. NSAA also higher than normal group. The ratio of Treg in children with SAA and NSAA was less than that in normal group (P all < 0.01). However, the ratio of Th17, Treg, Th17/Treg, and the levels of IL-6 and IL-17 had no significant difference between SAA and NSAA (all P > 0.05). (4) In different stages of treatment, such as diagnosis, transfusion-indenpendence, complete response, there were significant differences in the ratio of Th17 and Th17/Treg (both P < 0.05) but not in Treg (P > 0.05).

CONCLUSIONThe imbalance of Th17/Treg cells and abnormally increased cytokines related to Th17 cells exist in peripheral blood of AA children, but did not significantly affect the severity of AA in preliminary diagnosis. After treatment with immunosuppression, AA was gradually relieved as the imbalance of Th17/Treg was corrected.

Adolescent ; Anemia, Aplastic ; immunology ; therapy ; Blood Transfusion ; Child ; Child, Preschool ; Cytokines ; Female ; Flow Cytometry ; Humans ; Interleukin-17 ; Interleukin-6 ; Male ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

Objective To analyze the outcome of childhood B-cell acute lymphoblastic leukemia treated (ALL) with SCMC-ALL-2005 protocol. Methods Newly diagnosed B-cell ALL from May 1, 2005 to April 30, 2009 in ifve hospitals were treated and followed up according to SCMC-ALL-2005 protocol. Results A total of 601 cases with newly diagnosed B-cell ALL were enrolled. Among them, 539 cases (89.68%) were followed up until September 30, 2011. In 601 patients, there were 284 low-risk cases (LR group), 231 moderate-risk cases (MR group) and 86 high-risk cases (HR group) which were treated with SCMC-ALL-2005 protocol. The total complete remission rate during the period of induction was 98.84%and 7 cases did not achieve complete remission. The median time of the ifrst event occurring was 35 months (2.94 years). Among 539 cases completing follow-up, 403 cases (74.77%) completed treatment including 223 cases (86.43%) in LR group, 150 cases (73.17%) in MR group and 30 cases (39.47%) in HR group. The rate of cases completing treatment was signiifcantly different among three groups (P=0.001). The completion rate was highest in LR group and lowest in HR group. The 3-year overall survival (OS) rate was (83.3±1.8)%, and the 3-year EFS (event-free survival) rate was (79.2±1.9)%using a Kaplan-Meier method. The 5-year OS rate was (79.5±3.3)%, and the 5-year EFS rate was (70.9±3.7)%. There were signiifcant differences in 3-year EFS rate and 5-year EFS rate among three groups (P<0.05). Conclusions Childhood B-ALL treated with SCMC-ALL-2005 protocol achieved a better therapeutic effect and prognosis. The multi-center collaborative research is useful for the standard treatment of ALL.