Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Human-animal parasitic diseases caused by medical helminths are hazardous to human health. Genetic polymorphism studies on medical helminth populations can not only understand the biological characteristics and genetic structure of their populations, but also help reveal how they adapt to their parasitic environment, thus contributing to deepen our understanding of the epidemiological patterns of parasitic diseases and improve our understanding of accurate prevention and control of parasitic diseases. With the development of molecular biology, molecular markers such as DNA barcodes, simple sequence repeats, and single nucleotide polymorphism markers have been widely used to study the genetic relationships among parasite populations and individuals, and to reveal the genetic variation of parasite populations and the evolution of species origins. In this paper, we systematically review the application of three molecular markers commonly used in the study of genetic polymorphism in medical helminths, with a view to laying the foundation for related research.

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.
Female ; Male ; Humans ; Child ; Decitabine ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Drug-Related Side Effects and Adverse Reactions ; Hematopoietic Stem Cell Transplantation

ObjectiveTo predict the potential targets and mechanism of Jingfang mixture in the treatment of H1N1 influenza and provide references for clinical application of Jingfang mixture. MethodThe active components and targets of Jingfang mixture against H1N1 influenza were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），SwissTargetPrediction， and TargetNet. The targets of H1N1 influenza were obtained from GeneCards，Online Mendelian Inheritance in Man （OMIM）， and DisGeNET and standardized by UniProt KB. The intersection targets were obtained by Venny 2.1.0. The "drug-component-target" network was constructed with Cytoscape 3.2.1 and analyzed for the topological attributes. The intersection targets were uploaded to STRING 11.5 to obtain the protein-protein interaction （PPI） network. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis were carried out by Metascape. Finally，the top active components ranked by degree were docked to the core targets by Autodock vina and visually analyzed by PyMOL. Balb/c female rats were used for experimental verification. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in lung tissues. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of tumor necrosis factor-α（TNF-α），interleukin-10（IL-10）， and interleukin-17（IL-17）. Real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels in lung tissues. ResultThere were 144 active components in Jingfang mixture. A total of 421 target genes of Jingfang mixture and 2 956 targets of H1N1 influenza were identified，including 199 common targets. Topological analysis showed that the core components of Jingfang mixture against H1N1 influenza included quercetin，luteolin， and kaempferol，and the core targets included prostaglandin-endoperoxide synthase 2（PTGS2），estrogen receptor alpha（ESR1），inducible nitric oxide synthase 2（iNOS2），peroxisome proliferator-activated receptorγ（PPARγ），and cyclooxygenase-1（PTGS1）. GO enrichment yielded 697 items in biological process （BP） （P<0.01）， 59 items in molecular function （MF）（P<0.01）， and 21 items in cellular component （CC） （P<0.01）. A total of 132 signaling pathways （P<0.01） were obtained by KEGG enrichment analysis， including phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway，most of which were related to the regulation of immune inflammation. Molecular docking showed that the binding energy of the active components of Jingfang mixture to the core targets was less than -5.0 kcal·mol^-1，indicating good binding activity. HE staining showed that the lung tissues were significantly improved after drug intervention，and Real-time PCR and Western blot showed that Jingfang mixture could reduce the mRNA and protein expression of PI3K and Akt in lung tissues. ConclusionJingfang mixture can play an anti-viral effect against the influenza A virus through multiple components，multiple targets， and multiple pathways. The active components quercetin，luteolin， and kaempferol may control the inflammation and regulate immunity on the PI3K/Akt，MAPK， and other signaling pathways by acting on targets such as PTGS2，ESR1，iNOS2，PPARγ， and PTGS1.

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m² of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Immunosuppressive Agents/adverse effects* ; Cyclophosphamide/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Administration, Intravenous ; Alopecia/drug therapy*

For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.

The UHPLC-LTQ-orbitrap-MS metabolomics technique was used to determine the effect of deapio-platycodin D (DPD) on endogenous metabolites in lung tissues of mice with ammonia-induced cough, and to identify the metabolic regulatory pathways of DPD in its antitussive and expectorant activities. This work was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235). Metabolites were identified by UHPLC-LTQ-orbitrap-MS method and the metabolic pathways related to differentially-expressed metabolites were analyzed by the MetaboAnalyst platform. DPD significantly prolonged (P < 0.05) cough latency, reduced the number of coughs, and significantly increased (P < 0.05) phenol red excretion in ammonia-induced cough mice. Twenty-five metabolites related to cough and 38 metabolites related to sputum excretion were identified by UHPLC-LTQ-orbitrap-MS. Changes in the metabolism of linoleic acid, arachidonic acid, glycerophospholipid, alanine, aspartic acid and glutamic acid, pentose and glucuronate interconversions, and lysine degradation were evident with DPD treatment of ammonia-induced cough mice. Changes in the metabolism of linoleic acid, taurine and hypotaurine, glycerophospholipid, purines and pyrimidines, arachidonic acid and the biosynthesis of unsaturated fatty acids after DPD treatment were related to phenol red excretion. Linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism are common regulatory pathways by which DPD appears to exert its antitussive and expectorant activity. These metabolic pathways are closely related to anti-inflammatory pathways, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and apoptosis. This study clarifies the antitussive and expectorant activity and mechanism of DPD.

OBJECTIVE: To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients. METHODS: B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients. RESULTS: There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×10⁹/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×10⁹/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10^-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×10⁹/L, bone marrow MRD >10^-4 at the 12th week were the independent risk factors affecting recurrence of the patients. CONCLUSION Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.
Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Male ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Recurrence ; Retrospective Studies

The present study quickly identified the ginsenosides in fresh Panax ginseng and specified the effects of different drying methods(50 ℃-drying, 80 ℃-drying, and-70 ℃ freeze-drying) on ginsenosides.Three P.ginseng products by different drying methods were prepared, and the UHPLC-Q-Exactive Orbitrap high-resolution liquid mass spectrometry(MS) technique was applied to perform gradient elution using water-acetonitrile as the mobile phase, and the data collected in the negative ion mode were analyzed using X Calibur 2.2.The results showed that 57 saponins were identified from fresh P.ginseng.As revealed by the comparison with the fresh P.ginseng, in terms of the loss of ginsenosides, the dried products were ranked as the dried product at 50 ℃, freeze-dried products at-70 ℃, and the dried product at 80 ℃ in the ascending order.This study elucidated the effects of different drying methods on the types and relative content of ginsenosides, which can provide references for the processing of P.ginseng in the producing areas.
Ginsenosides/analysis* ; Chromatography, High Pressure Liquid/methods* ; Panax ; Mass Spectrometry/methods* ; Saponins

OBJECTIVE: To investigate the effect of course delay of CCLG-ALL-2008 regimen on the relapse of paediatric B-cell acute lymphoblastic leukemia (B-ALL) patients. METHODS: Paediatric B-ALL patients newly diagnosed and treated with CCLG-ALL-2008 regimen in the Children's Hospital of Soochow University from January 2011 to December 2014 were retrospectively analyzed to clarify the relationship between chemotherapy course delay and relapse, and explore the causes of course delay which led to relapse. Patients were followed up until July 2019. RESULTS: The correlation between treatment delay (number of weeks) and relapse rate was statistically significant (P=0.034), and hazard ratio indicated that longer than 4 weeks had a significant effect. The effect of positive minimal residual disease (MRD) (1×10^-4≤MRD≤1×10^-2) at the 12th week on the relapse rate was also statistically significant (P=0.041). Among the causes of treatment delay, the effect of myelosuppression on the relapse rate was statistically significant (P=0.01). CONCLUSION Treatment delay exceeding 4 weeks, positive MRD at the 12th week, and myelosuppression are independent prognostic factors for relapse.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bone Marrow Diseases/drug therapy* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual/drug therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Recurrence ; Retrospective Studies ; Treatment Outcome