OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

Objective To investigate the distribution of mosquito species and their associated viruses, and identify Culex pipiens subspecies in Hami City, Xinjiang Uygur Autonomous Region. Methods Mosquitoes were captured using mosquito trapping lamps method in Yizhou District, Yiwu County, and Balikun County of Hami City in mi-July, 2019 and 2020. The species and subspecies of all captured mosquitoes were characterized. In addition, the flavivirus, alphavirus, bunyavirus, Japanese encephalitis virus, Liaoning virus, Tahyna virus, tick-borne encephalitis virus and West Nile virus were detected using reverse-transcription PCR assay in captured mosquitoes. Results A total of 1 496 mosquitoes were captured from Yizhou District, Yiwu County, and Balikun County of Hami City, belonging to 3 genus and 3 species. Cx. pipiens was the dominant mosquito species (986 mosquitoes, 65.91%), followed by Aedes caspius (457 mosquitoes, 30.55%), while Culiseta alaskaensis had the lowest number (53 mosquitoes, 3.54%). All captured Cx. pipiens mosquitoes were identified as Cx. pipiens pipiens based on the terminalia of male mosquitoes. RT-PCR assay tested negative for flavivirus, alphavirus, bunyavirus, Japanese encephalitis virus, Liaoning virus, Tahyna virus, tick-borne encephalitis or West Nile virus in captured Cx. pipiens mosquitoes. Conclusions There were 3 species of mosquitoes in Hami City from 2019 to 2020, including Cx. pipiens, Ae. Caspius and C. alaskaensis, with Cx. pipiens as the dominant mosquito species, and all captured Cx. pipiens mosquitoes were Cx. pipiens pipiens; however, no arboviruses were detected.

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

OBJECTIVE: To observe the effect of luteolin on the proliferation and expression of OPCML in breast cancer cell line MDA-MB-231. METHODS: Cultured MDA-MB-231 cells were treated with luteolin at the concentrations of 5, 10 and 20 μmol/L for 24 or 48 h. MTT assay was used to detect cell proliferation and flow cytometry was used to detect the cell apoptosis. The expressions of OPCML mRNA and protein were detected using real-time quantitative PCR and Western blotting, respectively. OPCML gene methylation in the promoter region was detected using methylation-specific PCR (MSP), and the activity of methylase in the cells was analyzed. RESULTS: MTT assay showed that treatment with luteolin at 5, 10 and 20 μmol/L for 24 h concentration-dependently decreased the viability of MDA-MB-231 cells ( < 0.05). Flow cytometry also showed that luteolin at different concentrations could induce apoptosis of MDA-MB-231 cells ( < 0.05). Luteolin dose-dependently induced the expression of OPCML mRNA and protein in MDA-MB-231 cells ( < 0.05), down-regulated the methylation status in the promoter region of OPCML gene, up-regulated the level of non-methylated OPCML, and reduced the activity of methylase in the cells ( < 0.05). CONCLUSIONS Luteolin inhibits the proliferation of MDA-MB-231 breast cancer cells probably by upregulating OPCML expression and its demethylation.
Apoptosis ; Breast Neoplasms ; Cell Adhesion Molecules ; Cell Line, Tumor ; Cell Proliferation ; GPI-Linked Proteins ; Humans ; Luteolin

OBJECTIVE: To study the expression levels of glial cell line-derived neurotrophic factor family receptor α-1 (GFRα1) and enhancer of zeste homolog 2 (EZH2) in the intestinal tissue of children with Hirschsprung's disease (HSCR), as well as the role of EZH2 in the regulation of GFRα1 gene expression and the pathogenesis of HSCR. METHODS: The samples of colon tissue with spasm from 24 children with HSCR after radical treatment of HSCR were selected as the experimental group, and the samples of necrotized colon tissue from 18 children with neonatal necrotizing enterocolitis after surgical resection were selected as the control group. Real-time PCR and Western blot were used to measure the expression levels of GFRα1 and EZH2 in colon tissue in both groups. Human neuroblastoma SH-SY5Y cells were divided into an EZH2 over-expression group and a negative control group. The cells in the EZH2 over-expression group were transfected with pCMV6-EZH2 plasmid, and those in the negative control group were transfected with pCMV6 plasmid. The expression levels of EZH2 and GFRα1 were measured after transfection. RESULTS: Compared with the control group, the experimental group had significant reductions in the mRNA and protein expression levels of GFRα1 and EZH2 in colon tissue (P<0.05), and the protein expression of EZH2 was positively correlated with that of GFRα1 (r=0.606, P=0.002). Compared with the negative control group, the EZH2 over-expression group had significant increases in the expression levels of EZH2 and GFRα1 after SH-SY5Y cells were transfected with EZH2 over-expression plasmid (P<0.05). CONCLUSIONS Low expression of EZH2 in the colon tissue of children with HSCR may be one of the causes of inadequate expression of GFRα1 and onset of HSCR.
Child ; Colon ; Enhancer of Zeste Homolog 2 Protein ; genetics ; Glial Cell Line-Derived Neurotrophic Factor Receptors ; genetics ; Hirschsprung Disease ; genetics ; Humans ; Infant, Newborn ; RNA, Messenger

Objective To assess the effectiveness of infectious source control at various stages of transmission control of schistosomiasis in Eryuan County of Yunnan Province, so as to provide insights into the further monitoring and management of infectious sources of schistosomiasis. Methods Wenbi Village, a plateau subtype region and Qiandian Village, a mountain subtype region in Eryuan County were selected as the study areas. The species, schistosome infection and transmission capability of infectious sources were investigated in Wenbi and Qiandian villages in 2011 and 2018 and were compared. Results Schistosome infections were detected in human, bovine, horse, dog and mouse in Qiandian Village in 2011, with positive rates of 1.19%, 0.91%, 1.25%, 3.13% and 0.95%, respectively, and human, bovine and dog were found to have schistosome infections, with positive rates of 0.76%, 1.66% and 9.30%, respectively. However, no infections were identified in human, bovine, horse, pig, dog, sheep or mouse in these two villages in 2018. A total of 731 wild feces were collected in both villages in 2011. In Qiandian Village, horse, bovine and dog feces accounted for 34.40%, 29.80% and 20.20% of all fecal samples, and dog and horse feces were found to have schistosome infections (11.94% and 6.90% positive rates, respectively). In Wenbi Village, dog, bovine and human feces accounted for 44.59%, 39.83% and 14.29% of all fecal samples, and dog, human and bovine feces were found to have schistosome infections (16.95%, 9.52% and 2.33% positive rates, respectively). In 2018, a total of 204 wild feces were collected in both villages, and no schistosome infections were identified. Sheep, dog and bovine feces accounted for 36.27%, 33.33% and 27.45% of all fecal samples in Qiandian Village, and dog, bovine and human feces accounted for 72.55%, 11.76% and 10.78% of all fecal samples in Wenbi Village. Conclusions A remarkable achievement has been obtained in the control of infectious sources of schistosomiasis in Eryuan County, and the role of human and bovine as the major infectious sources of schistosomiasis has been effectively controlled. In the future, the integrated strategy with emphasis on the control of infectious sources should be intensified, and the management of reservoir hosts including dog and mouse should be strengthened.

Objective: To explore the clinical efficacy of modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease (syndrome of phlegm-heat obstructing lung) and investigate its effects on serum tumor necrosis factor-alpha (TNF-α),interleukin-8(IL-8) and matrix metalloproteinase-9(MMP-9).Method: Sixty-four patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (32 cases) and treatment group (32 cases) by random number table.The control group was treated with routine western medicine therapy according to the guidance and disease conditions.Based on treatment in control group,patients in treatment group also received modified Qingqi Huatan Wan.The treatment course was 14 days for both groups.The scores of traditional Chinese medicine (TCM) syndrome,chronic obstructive pulmonary disease (COPD) assessment test (CAT),and modified version of the British Medical Research Council's Respiratory Questionnaire (mMRC),pulmonary function,blood gas analysis indicators,levels of serum TNF-α,IL-8 and MMP-9,clinical efficacy and safety were evaluated and compared once before treatment and 14 d after treatment.Result: The total clinical effective rate was 96.67% in treatment group,higher than 76.67% in control group (χ²=5.192,P<0.05).After treatment,scores of TCM syndrome,CAT and mMRC were reduced in both groups (P<0.05),and the scores in treatment group were all lower than those in control group (P<0.05).Levels of forced expiratory volume in one second (FEV₁),percent of FEV₁ in predicted value (FEV₁%),and ratio of FEV₁ to forced vital capacity (FEV₁/FVC) were increased in both groups after treatment (P<0.05),and the above levels in treatment group were higher than those in control group (P<0.05).After treatment,oxygen saturation (SaO₂) and partial pressure of oxygen (PaO₂) were increased in both groups,while partial pressure of carbon dioxide (PaCO₂) was decreased (P<0.05),and SaO₂ and PaO₂ in treatment group were higher than those in control group,while PaCO₂ was lower than that in control group (P<0.05).After treatment,serum TNF-α,IL-8 and MMP-9 were decreased in both groups (P<0.05),and the levels in treatment group were lower than those in control group (P<0.05).Conclusion: Modified Qingqi Huatan Wan can control the symptoms safely and ameliorate pulmonary function,reduce the levels of serum TNF-α,IL-8,MMP-9 and inflammation in treatment of AECOPD.

Objective:To explore the clinical efficacy of Modified Qingqi Huatan Wan in treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on inflammatory reaction, airway remodeling and thrombokinesis. Method:A total of 80 patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) were randomly divided into control group (40 cases) and therapy group (40 cases) by random number table. The control group was treated with conventional therapy. In addition to the therapy for the control group, the patients in therapy group also received modified Qingqi Huatan Wan. The treatment course was 14 days for both groups. Scores of traditional Chinese medicine(TCM) syndrome, chronic obstructive pulmonary disease and asthma physiology Score (CAPS), and chronic obstructive pulmonary disease patients self-assessment test questionnaire (CAT) were compared. The secondary indicators were pulmonary function, arterial blood gas analysis, and blood rheology indexes. In addition, the levels of serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), transforming growth factor-beta1 (TGF-β₁) and plasma tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-willebrand factor (v-WF), clinical efficacy and safety were evaluated. Result:The total clinical effective rate was 94.74% in therapy group,which was higher than 78.38% in control group (χ²=4.341,P<0.05). After treatment, scores of TCM syndrome, CAPS, CAT and levels of PaCO₂, serum NF-κB, IL-6, IL-8, MMP-2, TIMP-2, TGF-β₁ and plasma PAI-1, v-WF in therapy group were lower than those in control group(P<0.05). However, levels of plasma t-PA, SaO₂, PaO₂, FEV₁, FEV₁%, FEV₁/FVC in therapy group were higher than those in control group(P<0.05), therapy group was alleviated more than control group (P<0.05). Conclusion:Modified Qingqi Huatan Wan can control the symptoms safely, alleviate CAPS and lung function, effectively reduce the inflammatory response and inhibit the formation of airway remodeling and thrombosis, and its mechanism may be protect the lung tissue by reducing the level of inflammatory cytokines, regulating the balance of MMP-2/TIMP-2 and t-PA/PAI-1 and improving extracellular matrix and vascular endothelial function.

The Oncomelania hupensis snails were dually infected with Exorchis mupingensis and Schistosoma japonicum at different intervals for 21 d,37 d,55 d,70 d and 85 d.The results indicated that the development of all S.japonicum larvae were blocked in the snails of co-infection,and the complexity and number of secretions in and around all the wrecked S.japonicum larvae is proportional to the intervals of co-infection.In addition,we also described and compared the detailed change of snails' secretions in different conditions of infection,and determined that the snail's secretions may involve in the destruction and damage of S.japonicum larvae.The attack degrees on larval S.japonicum in O.hupensis snails dually infected by E.mupingensis and S.japonicum with longer intervals were stronger than that of shorter intervals,and snail haemo-lymphocytes numbers were more few in that of shorter intervals.But the secretions remarkably increased in more longer interval model experimental snail tissue.This finding may provide an alternative strategy for reducing and controlling the transmission of S.japonicum,and are very helpful for better understanding the host-parasite relationship.

Background:For Chinese patients with hepatocellular carcinoma (HCC),surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor,and yet the prognosis after surgery is diverse.We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.Methods:A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital.Age,hepatitis B surface antigen,hepatitis B e antigen,partial thromboplastin time,total bilirubin,alkaline phosphatase,γ-glutamyltransferase,α-fetoprotein,tumor size,cirrhosis,vascular invasion,differentiation,encapsulation,and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion.The Harrell's concordance index (C-index) was used to measure model performance.Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient.Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012,808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010,and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts.Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results:Shanghai Score showed good calibration and discrimination in postsurgical HCC patients.The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients),and in the three independent validation cohorts,the CIs for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68.Furthermore,Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α).The identified subset of patients at low risk could be ideal candidates for curative surgery,and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery.Finally,a web server with individualized outcome prediction and treatment recommendation was constructed.Conclusions:Based on the largest cohort up to date,we established Shanghai Score-an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery.The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.