Publications by authors named "Runming Jin"

61 Publications

Epidemiological investigation of hemophagocytic lymphohistiocytosis in China.

Orphanet J Rare Dis 2021 Aug 3;16(1):342. Epub 2021 Aug 3.

Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Currently, most research on hemophagocytic lymphohistiocytosis (HLH) have focused on etiology and therapy, leaving few epidemiological reports. The published studies of China are mainly regional investigations. We aimed to present the overall epidemiological status of HLH in China, and provide Chinese data for the international HLH epidemiological investigation.

Methods: The data of HLH cases in China in 2019 were collected and statistically analyzed.

Findings: Epstein-Barr virus accounted for 44.01% of the 1445 cases in 31 regions and was the most common cause. Lymphoma-associated HLH patients were more often male (P < 0.05) while rheumatic and immune-associated HLH were more often female (P < 0.001). Primary HLH and Epstein-Barr Virus-associated HLH were predominant in children (P < 0.001) while tumor-associated HLH was predominant in adults. Lymphoma-associated HLH was positively correlated with the age of onset (P < 0.01). The diagnosis rate of 29 areas had a significant correlation with per capita Gross domestic product (P < 0.05).

Conclusion: The different distribution of HLH etiology by age and gender contributes to the diagnosis of HLH by clinicians; The suboptimal diagnosis rate in regions with a high incidence of HLH in China is a result of the effect of the local economic level indicating the importance of improving the regional medical level.
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http://dx.doi.org/10.1186/s13023-021-01976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336372PMC
August 2021

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

Lancet Oncol 2021 09 27;22(9):1322-1332. Epub 2021 Jul 27.

Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China.

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia.

Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m) plus oral dexamethasone (6 mg/m per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706.

Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060).

Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia.

Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00328-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416799PMC
September 2021

Comparison of Clinical Characteristics Among COVID-19 and Non-COVID-19 Pediatric Pneumonias: A Multicenter Cross-Sectional Study.

Front Cell Infect Microbiol 2021 1;11:663884. Epub 2021 Jul 1.

Department of Pediatrics, Yichang Central People's Hospital, Yichang, China.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias.

Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test.

Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups.

Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.
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http://dx.doi.org/10.3389/fcimb.2021.663884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281119PMC
July 2021

Secondary Hemophagocytic Lymphohistiocytosis With Epstein-Barr Virus-Associated Transformed Follicular Lymphoma: A Case Report and Literature Review.

Front Oncol 2021 25;11:681432. Epub 2021 Jun 25.

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A 58-year-old male was admitted to our hospital due to lasting fever, progressive lymphadenopathy and bicytopenia, with a previously histological diagnosis of follicular lymphoma grade 3a with Epstein-Barr virus-encoded RNA positive one month ago. A second biopsy of axillary lymph node revealed concurrent diffuse large B-cell lymphoma with Epstein-Barr virus-encoded RNA positive. Another diagnosis of hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus positive diffuse large B-cell lymphoma was further concluded by clinical manifestation, laboratory test and atypical lymphocytes in peripheral-blood smear. After a pulse of steroid pre-phase treatment, the patient's clinical condition deteriorated and died in two weeks. The presence of Epstein-Barr virus infection in patients with follicular lymphoma is associated with more aggressive clinical course and increased risk of high-grade transformation. Hemophagocytic lymphohistiocytosis in response to Epstein-Barr virus infection or lymphoma remains fatal. Early diagnosis and initiation of treatment may improve the outcome.
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http://dx.doi.org/10.3389/fonc.2021.681432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267377PMC
June 2021

Role of Prealbumin in Predicting the Prognosis of Severely and Critically Ill COVID-19 Patients.

Am J Trop Med Hyg 2021 Jul 9. Epub 2021 Jul 9.

Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P.R. China.

Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150-400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital's electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.
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http://dx.doi.org/10.4269/ajtmh.21-0234DOI Listing
July 2021

Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.

J Clin Oncol 2021 Jun 2:JCO2003096. Epub 2021 Jun 2.

Anhui Provincial Children's Hospital, Hefei, China.

Purpose: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes.

Methods: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years.

Results: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment.

Conclusion: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.
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http://dx.doi.org/10.1200/JCO.20.03096DOI Listing
June 2021

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Sci Rep 2021 May 6;11(1):9656. Epub 2021 May 6.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
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http://dx.doi.org/10.1038/s41598-021-88912-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102476PMC
May 2021

Author Correction: Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

Cell Discov 2021 May 3;7(1):29. Epub 2021 May 3.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.

A Correction to this paper has been published: https://doi.org/10.1038/s41421-021-00267-0.
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http://dx.doi.org/10.1038/s41421-021-00267-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093281PMC
May 2021

Anthracycline Induced Cardiac Disorders in Childhood Acute Lymphoblastic Leukemia: A Single-Centre, Retrospective, Observational Study.

Front Pharmacol 2021 29;12:598708. Epub 2021 Mar 29.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Anthracycline-associated cardiotoxicity is frequently seen in cancer survivors years after treatment, but it is rare in patients on chemotherapy. This study aimed to investigate the clinical characteristics of cardiac disorders in children with acute lymphoblastic leukemia (ALL) during chemotherapy. A retrospective case study was conducted in children with ALL, for whom electrocardiogram (ECG) and echocardiography (Echo) were regularly assessed before each course of chemotherapy. The cardiac disorders were diagnosed according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Binary logistic regression analysis was used to identify risk factors associated with cardiac disorders. There were 171 children eligible for the study, and 78 patients (45.61%) were confirmed as having cardiac disorders. The incidence of cardiac disorders was dependent upon the cumulative dose of daunorubicin (DNR) ( = 0.030, OR = 1.553, 95% CI: 1.005-3.108). Four patients (2.34%) presented with palpitation, chest pain, and persistent tachycardia, and they were cured or improved after medical intervention. A total of 74 patients (43.27%) had subclinical cardiac disorders confirmed by ECG or Echo. ECG abnormalities were commonly seen in the induction and continuation treatments, including arrhythmias (26, 15.20%), ST changes (24, 14.04%) and conduction disorders (4, 2.34%). Pericardial effusion (14, 8.19%), left ventricular hypertrophy (11, 6.43%), a widened pulmonary artery (5, 2.92%) and valvular insufficiency (5, 2.92%) suggested by Echo occurred after induction chemotherapy. Therefore, cardiac disorders with clinical manifestations are rare and need early intervention. Subclinical cardiac disorders are common but very hidden in children during ALL chemotherapy. Regular ECG and Echo could help paediatricians to identify and monitor patients with asymptomatic cardiac disorders earlier.
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http://dx.doi.org/10.3389/fphar.2021.598708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039458PMC
March 2021

Probiotics in Cancer.

Front Oncol 2021 12;11:638148. Epub 2021 Mar 12.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

In recent years, the consumption of over-the-counter probiotics to promote health has grown rapidly worldwide and become an independent industry. In medicine, various studies have demonstrated that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotic clinical trials are contradictory. Particularly in cancer patients, the feasibility of probiotic management providing benefits by targeting cancer and lessening anticancer side effects requires further investigation. This review summarizes the interactions between probiotics and the host as well as current knowledge on the pros and cons of utilizing probiotics in cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.638148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006328PMC
March 2021

Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

Blood 2021 Jul;138(4):331-343

Departments of Oncology, Global Pediatric Medicine, Biostatistics and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).
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http://dx.doi.org/10.1182/blood.2020010438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323972PMC
July 2021

The Status of Pediatric Patients With Hematological Malignancy During COVID-19 Pandemic in Wuhan City, China.

J Pediatr Hematol Oncol 2021 Mar 31. Epub 2021 Mar 31.

Departments of Pediatrics Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Data regarding the epidemiologic characteristics and clinical features of pediatric hematological patients are limited in this corona virus disease 2019 (COVID-19) crisis. We investigated the status of 113 pediatric hematological patients in Wuhan union hospital during the COVID-19 pandemic from January 23 to March 10, 2020. All the patients had routine blood and biochemical examination, as well as chest computed tomography scans, and the nucleic acid, immunoglobulin G-immunoglobulin M combined antibodies tests for SARS-CoV-2. After admission, all patients were single-room isolated for 5 to 7 days. The results showed that only 1 (0.88%) child with leukemia was confirmed to have SARS-CoV-2 infection and 15 (13.2%) children were considered as suspected cases. Comparing to the nonsuspected patients, the suspected cases had lower white blood cell count, hemoglobin level, neutrophil count, serum calcium ion level and serum albumin concentration, as well as higher levels of C-reactive protein. All the suspected cases were ruled out of SARS-CoV-2 infection by twice negative tests for the virus. Therefore, the incidence of SARS-CoV-2 infection in hematological malignancy children was low during the COVID-19 pandemic in China. COVID-19 got early detected and the virus spread out in the ward was effectively blocked by increasing test frequency and using single-room isolation for 5 to 7 days after admission.
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http://dx.doi.org/10.1097/MPH.0000000000002133DOI Listing
March 2021

The impact of pegylated recombinant human growth hormone replacement therapy on glucose and lipid metabolism in children with growth hormone deficiency.

Ann Palliat Med 2021 Feb 5;10(2):1809-1814. Epub 2021 Jan 5.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: This study aimed to investigate the impact of pegylated recombinant human growth hormone (PEG-rhGH) replacement therapy on glucose and lipid metabolism in children with growth hormone deficiency (GHD).

Methods: A total of 17 children with a growth hormone deficiency were treated with PEG-rhGH (trade name Juyi' Erchun) via subcutaneous injection once a week before sleep for 3 months. The doses given were 0.2 and 0.15 mg/(kg·week). The injection sites included the upper arm, the front of the thigh, and the periumbilical area of the abdominal wall. Follow-ups were conducted every 3 months after the treatment to detect the metabolic indexes of the children's blood glucose and blood lipids. Growth and development indexes, thyroid function, and other indexes were also detected regularly. The glucose and lipid metabolism indexes of each child, including fasting blood glucose, glycosylated hemoglobin, fasting insulin, total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), were measured before the treatment and every three months after the treatment. The total detection time was 3-30 months.

Results: No significant differences in fasting blood glucose, glycosylated hemoglobin, fasting insulin, total cholesterol, triglycerides, HDL, and LDL were detected after the treatment when compared with measurements taken before the treatment (P>0.05).

Conclusions: PEG-rhGH replacement therapy may have no significant impact on glucose and lipid metabolism in children with GHD. However, this conclusion needs to be verified through studies with larger samples and long-term follow-up periods.
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http://dx.doi.org/10.21037/apm-20-871DOI Listing
February 2021

Risk factors related to the severity of COVID-19 in Wuhan.

Int J Med Sci 2021 1;18(1):120-127. Epub 2021 Jan 1.

Department of Pediatric, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, P.R. China.

To evaluate the characteristics at admission of patients with moderate COVID-19 in Wuhan and to explore risk factors associated with the severe prognosis of the disease for prognostic prediction. In this retrospective study, moderate and severe disease was defined according to the report of the WHO-China Joint Mission on COVID-19. Clinical characteristics and laboratory findings of 172 patients with laboratory-confirmed moderate COVID-19 were collected when they were admitted to the Cancer Center of Wuhan Union Hospital between February 13, 2020 and February 25, 2020. This cohort was followed to March 14, 2020. The outcomes, being discharged as mild cases or developing into severe cases, were categorized into two groups. The data were compared and analyzed with univariate logistic regression to identify the features that differed significantly between the two groups. Based on machine learning algorithms, a further feature selection procedure was performed to identify the features that can contribute the most to the prediction of disease severity. Of the 172 patients, 112 were discharged as mild cases, and 60 developed into severe cases. Four clinical characteristics and 18 laboratory findings showed significant differences between the two groups in the statistical test (<0.01) and univariate logistic regression analysis (<0.01). In the further feature selection procedure, six features were chosen to obtain the best performance in discriminating the two groups with a linear kernel support vector machine. The mean accuracy was 91.38%, with a sensitivity of 0.90 and a specificity of 0.94. The six features included interleukin-6, high-sensitivity cardiac troponin I, procalcitonin, high-sensitivity C-reactive protein, chest distress and calcium level. With the data collected at admission, the combination of one clinical characteristic and five laboratory findings contributed the most to the discrimination between the two groups with a linear kernel support vector machine classifier. These factors may be risk factors that can be used to perform a prognostic prediction regarding the severity of the disease for patients with moderate COVID-19 in the early stage of the disease.
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http://dx.doi.org/10.7150/ijms.47193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738952PMC
January 2021

Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

Cell Discov 2020 Dec 22;6(1):96. Epub 2020 Dec 22.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.
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http://dx.doi.org/10.1038/s41421-020-00235-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752915PMC
December 2020

Recommendations for the Diagnosis, Prevention, and Control of Coronavirus Disease-19 in Children-The Chinese Perspectives.

Front Pediatr 2020 5;8:553394. Epub 2020 Nov 5.

Department of Pediatrics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Ever since SARS-CoV-2 began infecting people by the end of 2019, of whom some developed severe pneumonia (about 5%), which could be fatal (case fatality ~3.5%), the extent and speed of the COVID-19 outbreak has been phenomenal. Within 2.5 months (by March 18, 2020) over 191,127 COVID-19 patients have been identified in 161 countries. By then, over 700 pediatric patients were confirmed to have COVID-19 in China, with only about 58 diagnosed elsewhere. By now, there are thousands of children and adolescents infected. Chinese pediatricians would like to share their experience on how these patients were managed in China and the key recommendations that had guided them in meeting the evolving challenges. A group of experts were summoned by the Chinese Pediatric Society and Editorial Board of Chinese Journal of Pediatrics to extract informative data from a survey on confirmed COVID-19 pediatric patients in China. Consensus on diagnosis, management, and prevention of pediatric COVID-19 were drawn up based on the analysis of such data plus insights gained from the past SARS and MERS coronavirus outbreaks. Relevant cumulating experiences from physicians managing adult patients, expedited reports on clinical and scientific COVID-19 and SARS-CoV-2 data, and the National Health Committee guidelines on COVID-19 management were integrated into this proposal.
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http://dx.doi.org/10.3389/fped.2020.553394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674551PMC
November 2020

CSF-1R inhibition disrupts the dialog between leukaemia cells and macrophages and delays leukaemia progression.

J Cell Mol Med 2020 11 10;24(22):13115-13128. Epub 2020 Oct 10.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Research in the last few years has revealed that leukaemic cells can remodel the bone marrow niche into a permissive environment favouring leukaemic stem cell expansion. Tumour-associated macrophages (TAMs) are prominent components of the tumour microenvironment and play an important role in the onset and progression of solid tumours. However, little is known about their role in the development of acute lymphoblastic leukaemia (ALL). Using a unique mouse model of T-ALL induced by injection of EL4 T-cell lymphoma cells to syngeneic C57BL/6 mice, we report herein that ALL leads to the invasion of leukaemia-associated monocyte-derived cells (LAMs) into the bone marrow and spleen of T-ALL mice. Furthermore, we found that leukaemia cells could polarize bone marrow-derived macrophages (BMDMs) into LAMs. In turn, LAMs were able to protect leukaemia cells from drug-induced apoptosis in vitro. Therapies targeted against the TAMs by inhibiting colony stimulating factor-1 receptor (CSF-1R) have emerged as a promising approach for cancer treatment. In this study, we demonstrate that CSF-1R inhibition inhibits the viability of BMDMs, blocks LAMs polarization and reduces the abundance of LAMs in T-ALL mice. In vivo, combination treatment of CSF-1R inhibitor and vincristine (VCR) dramatically increased the survival of T-ALL mice and delayed leukaemia progression compared with VCR monotherapy. Finally, these data reinforce the role of microenvironments in leukaemia and suggest that macrophages are a potential target for the development of novel therapeutic strategies in T-ALL.
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http://dx.doi.org/10.1111/jcmm.15916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701573PMC
November 2020

A flowchart strategy for children with leukemia during COVID-19: A nondesignated hospital's experience.

Pediatr Blood Cancer 2021 01 25;68(1):e28563. Epub 2020 Jul 25.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1002/pbc.28563DOI Listing
January 2021

High-Dose Methotrexate-Induced Idiopathic Intracranial Hypertension in Infant Acute Lymphoblastic Leukemia.

Front Pharmacol 2020 17;11:839. Epub 2020 Jun 17.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A 7-month-old baby girl with acute lymphoblastic leukemia (ALL) presented with bulging anterior fontanelle after completing the first and second courses of high-dose methotrexate (HD-MTX) chemotherapy. Between courses, the infant recovered and was discharged. Prior to the third and fourth HD-MTX courses, the baby girl was administered infusions of dexamethasone, which prevented recurrence of neurological side effects observed after the first and second courses of HD-MTX. To our knowledge, this is the first reported case of HD-MTX-induced idiopathic intracranial hypertension in infants, and that prophylactic use of dexamethasone can be applied to prevent acute intracranial hypertension following HD-MTX infusion.
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http://dx.doi.org/10.3389/fphar.2020.00839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311754PMC
June 2020

Evaluation of Nutrition Risk and Its Association With Mortality Risk in Severely and Critically Ill COVID-19 Patients.

JPEN J Parenter Enteral Nutr 2021 01 20;45(1):32-42. Epub 2020 Jul 20.

Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.

Background: The nutrition status of coronavirus disease 2019 patients is unknown. This study evaluates clinical and nutrition characteristics of severely and critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigates the relationship between nutrition risk and clinical outcomes.

Methods: A retrospective, observational study was conducted at West Campus of Union Hospital in Wuhan. Patients confirmed with SARS-CoV-2 infection by a nucleic acid-positive test and identified as severely or critically ill were enrolled in this study. Clinical data and outcomes information were collected and nutrition risk was assessed using Nutritional Risk Screening 2002 (NRS).

Results: In total, 413 patients were enrolled in this study, including 346 severely and 67 critically ill patients. Most patients, especially critically ill patients, had significant changes in nutrition-related parameters and inflammatory markers. As for nutrition risk, the critically ill patients had significantly higher proportion of high NRS scores (P < .001), which were correlated with inflammatory and nutrition-related markers. Among 342 patients with NRS score ≥3, only 84 (of 342, 25%) received nutrition support. Critically ill patients and those with higher NRS score had a higher risk of mortality and longer stay in hospital. In logistic regression models, 1-unit increase in NRS score was associated with the risk of mortality increasing by 1.23 times (adjusted odds ratio, 2.23; 95% CI, 1.10-4.51; P = .026).

Conclusions: Most severely and critically ill patients infected with SARS-CoV-2 are at nutrition risk. The patients with higher nutrition risk have worse outcome and require nutrition therapy.
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http://dx.doi.org/10.1002/jpen.1953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361906PMC
January 2021

A De Novo Mutation in MYH9 in a Child With Severe and Prolonged Macrothrombocytopenia.

J Pediatr Hematol Oncol 2021 01;43(1):e7-e10

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

Congenital macrothrombocytopenia is a diverse group of hereditary disorders caused by mutations in the MYH9 gene, which encodes the nonmuscle myosin heavy chain-A, an important motor protein in hemopoietic cells. Thus, the term MYH9-related disease has been proposed, but the clinicopathologic basis of MYH9 mutations has been poorly investigated. Here, we report a sporadic case of Epstein syndrome, an MYH9 disorder, in a 4-year-old Chinese boy who presented with macrothrombocytopenia. He had no family history of thrombocytopenia, hearing loss, or renal failure. A de novo heterozygous MYH9 mutation, c.287C>T; p. (Ser96Leu), was found in this patient. Genotype-phenotype analysis of all reported mutations suggested a domain-specific relationship between the location of the MYH9 mutation and the penetrance of the nonhematologic characteristics of MYH9-related disorders. Our study highlights the importance of suspecting MYH9-related disease even in cases of chronic macrothrombocytopenia without a family history or extrahematologic symptoms.
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http://dx.doi.org/10.1097/MPH.0000000000001846DOI Listing
January 2021

Huai Qi Huang Potentiates Dexamethasone-Mediated Lethality in Acute Lymphoblastic Leukemia Cells by Upregulating Glucocorticoid Receptor α.

Med Sci Monit 2020 Feb 17;26:e921649. Epub 2020 Feb 17.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

BACKGROUND Glucocorticoids are important components of a number of chemotherapeutic regimens used to treat pediatric acute lymphoblastic leukemia (ALL). A primary cause of treatment failure of ALL is acquired resistance to glucocorticoids. Recently, traditional Chinese medicines were effectively used to treat solid tumors. Thus, the aim of this study was to investigate whether Huai Qi Huang (HQH), a traditional Chinese medicine, increased the efficacy of glucocorticoids in the treatment of ALL, and if so, to determine the underlying mechanism. MATERIAL AND METHODS Various concentrations of HQH were used to treat Jurkat and Nalm-6 cells for 24 to 72 hours. Subsequently, cells were co-treated with HQH and the glucocorticoid receptor agonist, dexamethasone (DEX), or a MEK inhibitor (PD98059) to verify the synergistic effects on apoptosis in Jurkat and Nalm-6 cells for 24 hours. Cell Counting Kit-8 assay and flow cytometry were used to measure cell viability and apoptosis, respectively. Protein and mRNA expression levels were assessed using western blotting and quantitative polymerase chain reaction. RESULTS The results revealed that cell survival was reduced and apoptosis was increased as the HQH concentration was increased, and this was accompanied with increases in the levels of BAX, cleaved-caspase-3 and glucocorticoid receptor alpha (GRalpha) and decreases in the levels of Bcl-2 and phospho-ERK (pERK). Glucocorticoid receptor ß (GRß) and total ERK (t-ERK) had no significant changes. Combined treatment with HQH and DEX or PD98059 increased apoptosis in Jurkat and Nalm-6 cells, and concurrently increased BAX, cleaved-caspase-3, GILZ, NFKBIA, and GRalpha and decreased Bcl-2 and pERK. CONCLUSIONS HQH enhanced the sensitivity of ALL cells to glucocorticoids by increasing the expression of GRalpha and inhibiting the MEK/ERK pathway, thus providing a rational foundation for the treatment of ALL with HQH.
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http://dx.doi.org/10.12659/MSM.921649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043341PMC
February 2020

Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement.

World J Pediatr 2020 06 7;16(3):223-231. Epub 2020 Feb 7.

Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts' committee to formulate this experts' consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children.
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http://dx.doi.org/10.1007/s12519-020-00343-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090771PMC
June 2020

Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: A multicenter study CCCG-ALL-2015.

Cancer Med 2020 03 28;9(6):2113-2121. Epub 2020 Jan 28.

Department of Paediatrics, Hong Kong Children's Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied.

Methods: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected.

Results: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%.

Conclusion: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.
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http://dx.doi.org/10.1002/cam4.2889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064088PMC
March 2020

Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

JAMA Oncol 2020 03;6(3):358-366

State Key Laboratory of Experimental Hematology and Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin, China.

Importance: A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

Objective: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation.

Design, Setting, And Participants: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019.

Interventions: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy.

Main Outcomes And Measures: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival.

Results: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups.

Conclusions And Relevance: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.
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http://dx.doi.org/10.1001/jamaoncol.2019.5868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720PMC
March 2020

Multitarget and promising role of dihydromyricetin in the treatment of metabolic diseases.

Eur J Pharmacol 2020 Mar 20;870:172888. Epub 2019 Dec 20.

Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jie Fang Avenue, Wuhan, Hubei Province, 430022, China. Electronic address:

Dihydromyricetin (DMY or DHM), also known as ampelopsin, is the main natural flavonol compound extracted from the plant Ampelopsis grossedentata (Hand. -Mazz) W.T. Wang. In recent years, accumulating studies have been conducted to explore the extensive biological functions of DMY, including antitumor, anti-inflammation, organ-protective, and metabolic regulation effects. DMY acts as a potential preventive or therapeutic agent in treating multiple diseases, such as diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease and osteoporosis. This review article summarizes the preventive and therapeutic potential of DMY in multiple metabolic diseases and the main signaling pathways in which DMY participates to offer a comprehensive understanding and guidance for future studies.
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http://dx.doi.org/10.1016/j.ejphar.2019.172888DOI Listing
March 2020

Integrin β4-Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis.

Cancer Res 2020 02 16;80(4):771-783. Epub 2019 Dec 16.

Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.

Integrin β4 (ITGB4) has been shown to play an important role in the regulation of cancer stem cells (CSC). Immune targeting of ITGB4 represents a novel approach to target this cell population, with potential clinical benefit. We developed two immunologic strategies to target ITGB4: ITGB4 protein-pulsed dendritic cells (ITGB4-DC) for vaccination and adoptive transfer of anti-CD3/anti-ITGB4 bispecific antibody (ITGB4 BiAb)-armed tumor-draining lymph node T cells. Two immunocompetent mouse models were utilized to assess the efficacy of these immunotherapies in targeting both CSCs and bulk tumor populations: 4T1 mammary tumors and SCC7 head and neck squamous carcinoma cell line. Immunologic targeting of ITGB4 utilizing either ITGB4-DC or ITGB4 BiAb-T cells significantly inhibited local tumor growth and metastases in both the 4T1 and SCC7 tumor models. Furthermore, the efficacy of both of these ITGB4-targeted immunotherapies was significantly enhanced by the addition of anti-PD-L1. Both ITGB4-targeted immunotherapies induced endogenous T-cell cytotoxicity directed at CSCs as well as non-CSCs, which expressed ITGB4, and immune plasma-mediated killing of CSCs. As a result, ITGB4-targeted immunotherapy reduced not only the number of ITGB4 CSCs in residual 4T1 and SCC7 tumors but also their tumor-initiating capacity in secondary mouse implants. In addition, treated mice demonstrated no apparent toxicity. The specificity of these treatments was demonstrated by the lack of effects observed using ITGB4 knockout 4T1 or ITGB4-negative CT26 colon carcinoma cells. Because ITGB4 is expressed by CSCs across a variety of tumor types, these results support immunologic targeting of ITGB4 as a promising therapeutic strategy. This study identifies a novel mechanism of resistance to anti-PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-1145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024642PMC
February 2020

New attempts for central nervous infiltration of pediatric acute lymphoblastic leukemia.

Cancer Metastasis Rev 2019 12;38(4):657-671

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The cure rate of acute lymphoblastic leukemia (ALL), the commonest childhood cancer, has been sharply improved and reached almost 90% ever since the central nervous system (CNS)-directed therapy proposed in the 1960s. However, relapse, particularly in the central nervous system (CNS), is still a common cause of treatment failure. Up to now, the classic CNS-directed treatment for CNS leukemia (CNSL) has been aslant from cranial radiation to high-dose system chemotherapy plus intrathecal (IT) chemotherapy for the serious side effects of cranial radiation. The neurotoxic effects of chemotherapy and IT chemotherapy have been reported in recent years as well. For better prevention and treatment of CNSL, plenty of studies have tried to improve the detection sensitivity for CNSL and prevent CNSL from happening by targeting cytokines and chemokines which could be key factors for the traveling of ALL cells into the CNS. Other studies also have aimed to completely kill ALL cells (including dormant cells) in the CNS by promoting the entering of chemotherapy drugs into the CNS or targeting the components of the CNS niche which could be in favor of the survival of ALL cells in CNS. The aim of this review is to discuss the imperfection of current diagnostic methods and treatments for CNSL, as well as new attempts which could be significant for better elimination of CNSL.
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http://dx.doi.org/10.1007/s10555-019-09827-zDOI Listing
December 2019

Metatropic Dysplasia of Nonlethal Variant in a Chinese Child - A Case Report.

Orthop Surg 2020 Feb 6;12(1):333-336. Epub 2019 Dec 6.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Metatropic dysplasia (MD), is a rare skeletal dysplasia occurring predominantly in infants characterized by a distinctive long torso and short limbs; it is as a result of mutations in the TRPV4 gene. However, a clear distinction between various forms of skeletal dysplasias caused by the transient receptor potential vanilloid 4 (TRPV4) gene is difficult but could be achieved by a combination of gene sequencing, medical and radiological criteria. We hereby report a case of a 14-month old girl who presented with an abnormal stature. The diagnosis of nonlethal MD was confirmed by X-ray with dumbbell-shaped long bones, platyspondyly, and delayed carpal ossification, as well as broadened pelvis with marginally widened ilia, epiphyseal plates, and slightly flattened acetabula. Furthermore, gene sequencing confirmed gene mutation on exon 15 of the TRPV4 gene with a heterozygous missense mutation (c.2396C > T), but no mutation was present in her parents. Our findings recorded metatropic dysplasia with the c.2396C > T mutation in the TRPV4 gene in China. This mutation caused changes in amino acid of TRPV4, which can induce growth retardation in children.
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http://dx.doi.org/10.1111/os.12546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031589PMC
February 2020

Congenital dyserythropoietic anemia type I mimicking myelodysplasia syndrome with a novel CDAN1 mutation.

Ann Hematol 2020 Jan 23;99(1):197-199. Epub 2019 Nov 23.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1007/s00277-019-03848-yDOI Listing
January 2020
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