OBJECTIVE: To explore the effects of hydroxychloroquine (HCQ) on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia (AML) and its molecular mechanism. METHODS: Bone marrow or peripheral blood samples of 36 AML patients with severe infection (AML-SI) and 29 AML patients without infection (AML-NI) after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023. In addition, the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group. The mRNA expressions of CXCL12, CXCR4 and CXCR7 were detected by RT-qPCR technology, and the levels of IL-6, IL-8 and TNF-α were detected by ELISA. Leukemia-derived THP-1 cells were selected and constructed as AML disease model. At the same time, bone marrow mesenchymal stem cells (BM-MSCs) from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group. THP-1 cells were treated with different concentration gradients of HCQ. The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry. ELISA was used to detect the changes of IL-6, IL-8 and TNF-α levels in the supernatant of the cell co-culture system, RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis, and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins. RESULTS: CXCL12, CXCR4, CXCR7, as well as IL-6, IL-8, and TNF-α were all abnormally increased in AML patients, and the increases were more significant in AML-SI patients (P <0.01). Furthermore, there were statistically significant differences between AML-NI patients and AML-SI patients (all P <0.05). HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells, but the low concentration of HCQ had no significant effect on the killing of THP-1 cells. When THP-1 cells were co-cultured with BM-MSCs of AML patients, the levels of IL-6, IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group (all P <0.01). After HCQ intervention, the levels of IL-6, IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention (all P <0.01). Similarly, those of Co-culture group were also significantly decreased (all P <0.001). However, the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ. HCQ could up-regulate the expression of pro-apoptotic protein Bax, down-regulate the expression of anti-apoptotic protein Bcl-2, as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κB pathway, then induce the programmed death of THP-1 cells after intervention. CONCLUSION The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients. HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells. The mechanisms may be related to regulating the expression of Bcl-2 family proteins, hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κB signaling pathway.
Humans ; Leukemia, Myeloid, Acute/immunology* ; Hydroxychloroquine/pharmacology* ; Receptors, CXCR4/metabolism* ; Apoptosis/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Chemokine CXCL12/metabolism* ; Interleukin-8/metabolism* ; Interleukin-6/metabolism* ; Receptors, CXCR/metabolism* ; Mesenchymal Stem Cells ; THP-1 Cells

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

OBJECTIVE: To test the reliability and validity of the Chinese version of parenting sense of competence scale (PSOC) in Chinese mothers of preschool children, and to explore the perception of preschool children's mothers on their own parenting skills and their comfort of being a parent in Yanqing District of Beijing. METHODS: A cross-sectional survey was conducted using a convenience sample in 1 384 preschool children's mothers in Yanqing District of Beijing. SPSS 21.0 and Mplus 7.4 software were used for statistical analysis to test the structural validity, criterion related validity, internal consistency and split half reliability of the scale, and to analyze the score of the scale and its influencing factors. RESULTS: The PSOC had good reliability and validity. Exploratory factor analysis showed that each item of the PSOC had more than 0.4 factor loading in efficacy factor or satisfaction factor, and there was no double load phenomenon. Confirmatory factor analysis showed that the factor loadings ranged from 0.212 to 0.843 in efficacy factor and satisfaction factor, respectively. The goodness of fit test showed that all the fitting indexes were within the acceptable range, and the correlation between the effectiveness subscale and the satisfaction subscale was high. The Cronbach's α coefficient of the whole scale, the efficacy subscale and the satisfaction subscale were 0.872, 0.802, and 0.874, respectively. The Spearman-Brown coefficient of PSOC was 0.851. The average score of the whole scale, the efficacy subscale, and the satisfaction subscale were 72.33±11.31, 35.54±5.91, and 36.79±7.11, respectively, and the score of parenting competence in Chinese mothers of preschool children was influenced by the mother's educational level and the annual income of her family. CONCLUSION The PSOC has satisfactory reliability and validity in Chinese mothers of preschool children. It can be used as an evaluation instrument for measuring the parenting competency, self perceived efficacy and satisfaction in the mainland Chinese mothers of preschool children. The competency of preschool children's mothers in Yanqing District of Beijing is very good, which may be related to the higher education level of the mothers and the higher annual income of their families in this study.
Beijing ; Child, Preschool ; China ; Cross-Sectional Studies ; Female ; Humans ; Mothers ; Parenting ; Psychometrics ; Reproducibility of Results ; Surveys and Questionnaires

"Kidney essence" is a profound concept in the theory of traditional Chinese medicine. But its biological basis is unknown until now, resulting in the therapeutic effects of traditional Chinese drugs on reinforcing kidney for supplementing essence hard to be evaluated. This study aimed, to explore the potential biological basis and mechanism of traditional Chinese drugs of reinforcing kidney for supplementing essence on diseases related to deficiency of kidney essence through network pharmacology analysis on the intersection of targets of drugs and diseases. The targets for ingredients in Rehmanniae radix praeparata (RRP), Polygoni multiflori radix praeparata (PMRP) and Polygonati rhizome (PR) were gathered from TCMSP and TCMID database. Osteoporosis, Alzheimer's disease, anemia, infertility and oligospermia targets were collected from OMIM and DisGeNET database. Drug-compound-target-disease (DCTD) network was established with Cytoscape 3.6.1 software, then Clue GO and DAVID database was used to acquire the annotation about GO terms and signaling pathways. Natural aging mice, an acknowledged syndrome model of deficiency of kidney essence, and RRP were used to verify the predictive targets by Western blot analysis. All animal experiments were conducted in accordance with the international guidelines and regulations for the care and use of animals. DCTD network showed that the intersection of drugs and diseases included 175 common targets. After topology analysis, 71 key were screened out targets which were associated with GO annotation exhibited that biological processes (including transcription regulation, RNA metabolism regulation, and DNA-dependent transcription regulation), cell composition (including nuclear lumen, organelle lumen, and membrane closure lumen), molecular function (including transcription regulation, transcription factor activity, and enzyme binding), and signaling pathway (including peroxisome proliferator-activated receptor alpha (PPARα), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and other signaling pathways. In natural aging mice, the expressions of HIF-1α, growth factor receptor-bound protein 2 (GRB2), MAPK3, signal transducer and activator of transcription 5A (STAT5A), transcription factor AP-1 (JUN) and proto-oncogene c-Fos (FOS) in EPO pathway were significantly decreased. RRP significantly reversed the decrease of the above targets. Above all, these results indicated that the therapeutic effects of traditional Chinese drugs of reinforcing kidney for supplementing essence on deficiency of kidney essence may be related to the regulation of nuclear transcriptional activity and EPO signaling pathway.

Objective To evaluate the potential risk of schistosomiasis transmission so as to provide the evidence for formulating the control strategy. Methods Two villages were selected as the investigated sites in Chuxiong City and the risk of schistosomiasis transmission was evaluated by reviewing the data of schistosomiasis epidemic situation and prevention and control work, and carrying out the field survey for Oncomelania hupensis snail status, wild faeces, and schistosome infection of the population from 2015 to 2017. Results There was 1.49 hm² area of snail habitats, with an average density of 0.54 snails/0.1 m². The occurrence rate of frames with snails was 5.41%. No schistosome-infected snails were found. The positive rate of schistosomiasis serological tests of the residents was 3.36%, but the stool examination positive cases were not found. A total of 58 wild faeces samples were collected but no schistosome infested cases were found. The risk levels of schistosomiasis transmission in both villages were Grade III. Conclusions Although Chuxiong City has been in a low risk state of schistosomiasis transmission, the density of snails is still high, and there is a risk of infection source importation. In the future, the infection source control and snail control should be strengthened.

Rosmarinic acid is one of anti-tumor ingredients in the Sarcandra glabra. After treatment with 0, 10, 30, 90, 270 and 810 μmol·L⁻¹ rosmarinic acid for 24, 48, 72 hours respectively, the inhibitory effects on MCF-7 and MDA-MB-231 cells were observed by CCK-8 and cell wound healing test. No significant inhibition effecton proliferation and migration was observed in MCF-7 cell. However, 90, 270 and 810 μmol·L⁻¹ rosmarinic acid could inhibit the proliferation and migration of MDA-MB-231 cells in a dose-dependent and time-dependent manner. Flow cytometry was further used to detect apoptosis ratios of MDA-MB-231 cells after Annexin V-FITC/PI staining, and significant apoptosis was observed after rosmarinic acid treatment. Real-time PCR and Western blot tests were carried out to detect the expressions of apoptosis-related genes. The down-regulation of the Bcl-2 expression and the up-regulation of the Bax expression were observed in MDA-MB-231 cells after rosmarinic acid treatment. The results suggested that rosmarinicacid can inhibit the proliferation and migration, and induce the apoptosis of MDA-MB-231 cells, which may be correlated with the down-regulation of Bcl-2 gene and the up-regulation of Bax gene.

Objective To explore the application value of sedation-agitation scale (SAS) in broncoscopy in children by observing sedative drug dosage, adverse reactions and operator's satisfaction. Methods Children were divided into two groups, control group and SAS group, before broncoscopy. Midazolam was given a dose 0.10 ~ 0.30 mg/kg according to doctor's experience, without any assessment, while the SAS group were given an initial doses of Midazolam 0.10 mg/kg and then continued giving Midazolam until the SAS score reached 3 points to 4 points, but the maxium does less than 10 mg. The maxium dosage of Midazolam in both groups was less than 10 mg. Then compare the dosage and adverse reactions of Midazolam and operator's satisfaction between the two groups. Results 606 children were enrolled in the study, 364 were boys and 242 were girls. The age ranged from 1 month to 17 years, while the mean age was (3.97 ± 3.94) years. The body weights were from 2.4 kg to 56.0 kg, and the mean weight was (16.18 ± 10.65) kg. 301 children were included into control group and 305 children were included into SAS group. The gender composition, age range, department source and composition of the diseases of the two groups were compared, and the differences were not statistically significant. Compared with the control group, there was no severe adverse reaction such as respiratory depression or excessive sedation in the SAS group, and the average amount of Midazolam was lower than the dosage in control group [(0.21 ± 0.06) vs (0.26 ± 0.05) mg/kg];the intraoperative agitation, delirium, other adverse drug reactions and the number of involved in the operation, and operation time were reduced, while the differences were statistically significant. The operator's satisfaction is higher, but the difference was not statistically significant. Conclusions SAS can be used in assessment of conscious sedation level in children's bronchoscopy, and SAS can guide the individual use of Midazolam, reduce its dosage and adverse reactions,also can improve the operator's satisfaction during the operation. SAS is worthy of application in children's conscious sedation in bronchoscopy.

Studies on the enzymology of snails are important in the study of molluscicidal mechanism.The alteration of activi-ties of enzymes after molluscicidal treatment was reported in large numbers of papers.This paper reviews the progress of studies on the enzymology of snails under the treatment of molluscicides.

OBJECTIVETo investigate the association of drug resistance of Mycoplasma pneumoniae (MP) with DNA load and genotypes in children with MP pneumonia.

METHODSA total of 230 children who were hospitalized and diagnosed with MP pneumonia between January 2012 and December 2016 were enrolled. Throat swabs were collected from the 230 children, and a rapid drug sensitivity assay was used to determine the sensitivity of clinical isolates of MP to nine commonly used antibacterial agents. Quantitative real-time PCR was used to measure MP-DNA load in throat swabs. PCR sequencing was used to determine the genotype of 2063 locus of the MP 23S rRNA V domain.

RESULTSOf the 230 children, 86 (37.4%) had genotype A in 2063 locus, 134 (58.3%) had genotype G, 8 (3.5%) had genotype C, and 2 (0.9%) had genotype T. Mutant strains (genotype G+C+T) had a significantly higher MP-DNA load than wild-type strains (genotype A) (P<0.05). The strains resistant to erythromycin, azithromycin, clarithromycin, and clindamycin had a significantly higher MP-DNA load than non-resistant strains (P<0.05). MP had a high drug resistance rate to macrolide antibiotics. More than 60% of the cases with resistance to macrolides were found to have A2063G mutations. MP was rarely resistant to quinolones (less than 2%).

CONCLUSIONSMutations in 2063 locus of the MP 23S rRNA V domain may result in the resistance of MP to macrolides and the change in DNA load and can be used as a basis for selecting drugs for MP.

Child ; Child, Preschool ; DNA, Bacterial ; analysis ; Drug Resistance, Bacterial ; Female ; Genotype ; Humans ; Infant ; Male ; Mycoplasma pneumoniae ; drug effects ; genetics ; Pneumonia, Mycoplasma ; drug therapy ; microbiology