OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL). METHODS: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment. RESULTS: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10 CONCLUSION Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.
Child ; Child, Preschool ; DEAD-box RNA Helicases ; DNA Helicases ; Down Syndrome ; Female ; Humans ; Leukemia, Megakaryoblastic, Acute/genetics* ; Male ; Prognosis ; Retrospective Studies ; Trisomy

Objective:To compare the characteristics of four commonly adopted animal models of hyperuricemia （HUA） for traditional Chinese medicine （TCM） screening， so as to choose the adequate model for screening Chinese herbs and herbal compounds capable of lowering the uric acid. Method:Fifty-four male SD rats were randomly divided into nine groups， namely the normal group， hypoxanthine （HX） + oxonic acid potassium salt （OAPS） model group， yeast extract （YE） + OAPS model group， low-dose adenine （AD） + ethambutol （EMB） model group， high-dose AD + EMB model group， and four positive drug allopurinol （Allo） groups. The modeling lasted for 14 d. The levels of serum uric acid （SUA）， urinary uric acid （UUA）， serum creatinine （SCr）， urea nitrogen （BUN）， kidney injury molecule 1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL） were detected on the 3rd， 7th， and 14th days. Urine was collected on the 7th and 14th days to investigate changes in urine volume， and the crystals in the residual urine were observed under a polarizing microscope. After the modeling， the kidney was harvested and weighed， followed by pathological examination. Result:The urine volumes in the HX + OAPS model group and high-dose AD + EMB model group were significantly reduced （P<0.05）. The renal indexes of each model group， except for the YE + OAPS model group， were significantly elevated （P<0.05， P<0.01）. The increase in SUA of the HX + OAPS model group and YE + OAPS model group started later （P<0.05）. The KIM-1 and NGAL levels of the HX + OAPS model group rose significantly from the 7th day （P<0.05， P<0.01）， and the BUN increased significantly on the 14th day （P<0.05）. There was no significant difference in the above-mentioned indicators in the YE + OAPS model group. The SUA levels of the low- and high-dose AD + EMB model groups increased significantly on the 3rd day （P<0.05， P<0.01）， with a persistent increase found in the low-dose AD + EMB model group. Besides， the increase in BUN， KIM-1， and NGAL occurred later （P<0.05， P<0.01）. By contrast， the high-dose AD + EMB model group exhibited a transient increase in SUA. Moreover， the SCr， BUN， KIM-1， and NGAL elevation occurred earlier and were more obvious than those in the low-dose AD + EMB model group （P<0.01）. Remarkable histomorphological abnormalities were detected in the kidney of all model groups， except for the YE+OAPS model group， with the most severe injury present in the high-dose AD+EMB model group. Conclusion:The four models commonly used to screen TCM have their own characteristics. In the four models， the SUA elevation in the HX + OAPS model group and YE + OAPS model group started later， with the mild renal injury observed in the HX + OAPS model group instead of the YE + OAPS model group. The SUA of the low-dose AD + EMB model group increased rapidly and lasted for a long time， accompanied by mild renal injury. The SUA of the high-dose AD + EMB model group only showed a transient increase， accompanied by severe renal injury. The investigation on the characteristics and application of different models and the evaluation of these models based on sensitive and objective indicators are helpful for determining the suitable model for the screening of TCM targeting HUA in the future.

OBJECTIVE: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL). METHODS: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated. RESULTS: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281). CONCLUSION The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.
Antifungal Agents/therapeutic use* ; Child ; Humans ; Induction Chemotherapy ; Mycoses/drug therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Primary Prevention ; Triazoles

To study the mechanism of Huangqin decoction (HQT) in the treatment of ulcerative colitis (UC) by using network pharmacology, chemical components and targets related to the four herbs of Chinese meteria medical in HQT were searched through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) to construct the interaction network diagram of the target point of the compounds. The UC-related targets were screened through OMIM, TTD, and GeneCard databases. The compound-target network was constructed using Cytoseape_v3.7.1 software; based on the STRING database, a target interaction network for HQT for UC was constructed, and the core target of HQT for UC was selected based on topological parameters. GO (gene ontology) biological process enrichment analysis and KEGG (KEGG pathway analysis) pathway annotation analysis were performed on the disease and drug intersection targets using the R package clusterprofile version 3.12.0 in Bioconductor. The HQT compound-UC target network contains 128 compounds and corresponding targets 141. The core targets are AKTI, IL6, PTGS2, IL10, IL1β and so on. GO functional enrichment analysis yielded 151 GO terms, and KEGG pathway enrichment screening resulted in 33 associations with UC, mainly involving PI3K-AKT signaling pathway, NF-kappa B signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. The synergetic effect of HQT with multi-components and multi-pathway was confirmed by network pharmacology, and the main possible mechanism of HQT in treating UC was predicted, which lay a foundation for the identification of effective components, the mechanism of action, and clinical application.

Objective:This study was designed to compare inflammatory response, water carriage and gut brain axis in rats with ulcerative colitis (UC) after treatment of three regiments, Huangqintang (HQT), Sishenwan (SSW), and Tongxie Yaofang(TXYF). Method:After approved by Institute of Chinese Materia Medica Ethics Committees in China Academy of Chinese Medical Sciences, UC in rats was induced by using a compound method (trinitrobenzenesulfonic acid plus ethanol). Rats were randomly divided into control, disease, positive control salazosulfapyridine (SASP, 0.5 g·kg^-1), HQT (20 g·kg^-1), SSW(26 g·kg^-1), and TXYF group(22 g·kg^-1). After 5 days of treatment, colonic tissues and the blood were taken for various assays. Damage of colonic tissues was detected by hematoxylin-eosin staining (HE). The distribution of Vasoactine intrestinal (VIP), 5-hydroxytrytamine (5-HT), P-substance (SP) in the blood and serum were detected by enzymelinked immunosorbent assay (ELISA) and immunohistochemistry (IHC), the levels of aquaporin3 (AQP3) and Aquaporin4 (AQP4) in the serum were detected by Western blot, the mRNA expression of Extracellular regulated protein kinases 1 (Erk1) and p38 mitogen-activated protein kinase (p38 MAPK) in the serum were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:The brain-gut peptide results showed that compared with the normal group, the content of 5-HT and VIP in model group were significantly decreased (P<0.01), the content of SP were decreased, but there was no significant statistical difference, compared with the disease group, the content of 5-HT in SASP and TXYF group were clearly increased (P<0.05), the increment of VIP and SP in SASP, HQT, TXYF group were significant (P<0.05). Compared with the normal group, the content of AQP3 in model group were significantly increased(P<0.01), the content of AQP4 were clearly decreased(P<0.01), compared with the disease group, the content of AQP4 in SASP and HQT group were clearly increased (P<0.05), whereas the levels of AQP3 in HQT group were most significant reduced (P<0.01). Compared with the disease group, the expression of Erk1 and p38 were clearly reduced (P<0.01), with the most significant reduce being the expression in HQT group. Conclusion:Three regiments all have therapeutic effects on UC, manifested by improvements of the signs and mental status of UC rats. However, in terms of gut-brain axis disturbance improvement, the therapeutic effect of TXYF was superior than HQT and SSW, whereas in terms of inflammatory response suppression and water carriage accomodation, the therapeutic effect of HQT was superior than SSW and TXYF.