5D-QSAR studies of 1H-pyrazole derivatives as EGFR inhibitors.

Epidermal growth factor receptor (EGFR) is highlighted as a target for anticancer treatment. Several EGFR inhibitors were approved in cancer treatment. Comparatively, 5D-QSAR is a new methodology which considers an ensemble of different induced-fit models. Based on 1H-pyrazole derivatives as EGFR inhibitors, a 5D-QSAR was studied in which the method of quasi-atomistic receptor surface modeling was used. The presented QSAR model showed contributions of the hydrogen bond acceptor, and hydrophobic and salt bridge fields to the activity. The QSAR model was statistically validated and also externally validated applying 19 compounds (test set) which were not included in the model generation process. The scramble tests were performed to further verify the robustness. Apart from exploration of the binding of 1H-pyrazole derivatives to the EGFR, the 5D-QSAR model can be helpful to design of new EGFR inhibitors. The five-dimensional quantitative structure-activity relationship (5D-QSAR) of 1H-pyrazole derivatives as EGFR inhibitors with quasi-atomistic receptor surface modeling approach is described.

Analysis of enterovirus genotypes in the cerebrospinal fluid of children associated with aseptic meningitis in Liaocheng, China, from 2018 to 2019.

BACKGROUND: Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. METHODS: We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. RESULTS: A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. CONCLUSIONS: This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.

Low-Dose Prednisone Treatment for IVIG-Resistant Kawasaki Disease with Severe Arthritis and Joint Effusion in Two 3-Year-Old Children.

Kawasaki disease (KD) is a global disease in children. The etiology and pathogenesis are unknown. Complications vary among patients. Fever can persist in some after immune globulin (IVIG) administration, termed IVIG-resistant KD. Here, we report two cases of IVIG-resistant KD with severe arthritis. The diagnosis of arthritis was confirmed by magnetic resonance imaging (MRI) showing joint effusion. Remarkably, fever and joint pain had not receded after the second dose of IVIG. To further manage the symptoms, we prescribed low-dose oral prednisone with success. Both fever and joint pain were diminished. We ponder that the low-dose prednisone might be an option to treat IVIG-resistant KD with severe arthritis.

Determinants of deranged thyroid function parameters in children admitted for management of diabetic ketoacidosis/diabetic ketosis.

BACKGROUND: Euthyroid sick syndrome (ESS) frequently arises in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children suffering from DKA/DK. METHODS: 98 DKA and 96 DK pediatric patients were selected from hospital records. Those on thyroxine replacement, with overt hypothyroidism, or with positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done on all patients. Children were divided into euthyroid (n = 88) and ESS groups (n = 106). RESULTS: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (ß-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P < 0.05). Free T3 (FT3) levels were significantly correlated to ß-HB, HCO3-, AG, PA, and HbA1c (r = - 0.642, 0.681, - 0.377, 0.581, - 0.309, respectively; P < 0.01). Free T4 (FT4) levels were significantly correlated to ß-HB, HCO3-, and ALB levels (r = - 0.489, 0.338, 0.529, respectively; P < 0.01). TSH levels were significantly affected by HCO3- only (r = - 0.28; P < 0.01). HCO3- level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR = 0.844, P = 0.004, 95%CI = 0.751-0.948). CONCLUSIONS: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.

Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line.

OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. RESULTS: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. CONCLUSION: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia.

Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line.

OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. RESULTS: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. CONCLUSION: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia[PARANDCO1].

The impact of Tegillarca granosa extract haishengsu on HL-60 cell.

Haishengsu (Hss) is a purified protein from Tegillarca granosa that has been used as a traditional Chinese medicine to treat cancer for more than a century. In this study, we observed the impact of Haishengsu (Hss) on the proliferation and differentiation of HL-60 cells in the leukemic cell line by taking tretinoin and AS2O3 as a positive control and making a comparative analysis between the effect of Hss and tretinoin and AS2O3. We found that Hss could significantly inhibit the proliferation of HL-60 cells and caused most of the cells to stay in the G0/G1 phase. Its effect was much stronger than that of tretinoin and AS2O3, and the ability of Hss to induce differentiation was close to tretinoin. Hss functions probably by inhibiting the expression of the Bcl-2 and MPO genes and further promoting the expression of the Bax gene. Hss has a significant effect on both inhibiting the proliferation and inducing the differentiation of HL-60 cells. It is possible that Hss may be a new kind of clinical differentiation inducer.