Gene CaMDR1 is a member of the major facilitator superfamily (MFS),mediating multidrug resistance of Candida albicans,and can confer resistance to benomyl,fluconazole and so forth.In this review,the progress in structure and function of the protein code by gene CaMDR1 and the transcriptional regulation mechanisms of CaMDR1 are summarized.

The objective of this study is to compare the normalized prediction distribution errors (NPDE) and the visual predictive check (VPC) on model evaluation under different study designs. In this study, simulation method was utilized to investigate the capability of NPDE and VPC to evaluate the models. Data from the false models were generated by biased parameter typical value or inaccurate parameter inter-individual variability after single or multiple doses with the same sampling time or multiple doses with varied sampling time, respectively. The results showed that there was no clear statistic test for VPC and it was difficult to make sense of VPC under the multiple doses with varied sampling time. However, there were corresponding statistic tests for NPDE and the factor of study design did not affect NPDE significantly. It suggested that the clinical data and model which VPC was not fit for could be evaluated by NPDE.
Animals ; Computer Simulation ; Humans ; Models, Biological ; Models, Statistical ; Nonlinear Dynamics ; Pharmaceutical Preparations ; administration & dosage ; metabolism ; Pharmacokinetics ; Predictive Value of Tests ; Software

Objective To analyze the clinical outcomes of a standard protocol of open reduction and internal fixation using a variable angle foot plate for a consecutive series of patients with acute Lisfranc joint injury.Methods This study retrospectively evaluated the clinical outcomes of 11 Chinese patients(13 feet) with acute Lisfranc joint injury who had been treated by open reduction and internal fixation with a variable angle foot plate from December 2016 to June 2017 at Department of Orthopaedics,West China Hospital.They were 8 men(10 feet) and 3 women(3 feet),aged from 19 to 57 years(average,36.4 years).Of them,10 were complicated with fracture of metatarsus,6 with cuneiform fracture and/or dislocation,4 with cuboid fracture,and one with cuboid fracture.According to the Myerson classification for Lisfranc fracture-dislocations,one case(one foot) belonged to type A,2(2 feet) to type Bl,5(6 feet) to type B2,2(3 feet) to type Cl and one(one foot) to type C2.The outcomes were evaluated using the visual analogue scale(VAS) and the midfoot scores of American Orthopedic Foot and Ankle Society(AOFAS).Results This cohort was followed up for 18 to 24 months(average,22 months).Their VAS scores were decreased significantly from preoperative 7.3±1.2(from 6 to 9) to postoperative 1.2±0.2(from 0 to 2)(P<0.05);their AOFAS midfoot scores were increased significantly from preoperative 0 to postoperative 84.6±4.6(P<0.05) Anatomic reduction was obtained in all the patients and all the fractures united successfully without any delayed union or nonunion.Superficial necrosis of the wound edge occurred in 2 cases without deep infection;skin anesthesia occurred in 2 and skin hypesthesia in 4,indicating a lesion of the superficial peroneal nerve.Conclusion Fixation of acute Lisfranc joint injury with a variable angle foot plate can lead to rigid stability,precise reduction and satisfactory short-term clinical outcomes.

OBJECTIVETo investigate the cell cycle changes of hepatoma cells and the effect of antisense oligonucleotide targeting bFGF on apoptosis in the hepatoma cells.

METHODSThe oligodeoxynucleotides were transfected with Lipofectin into hepatoma HepG2 cells. Inhibition of bFGF protein expression was assessed by confocal laser scanning microscopy and Western blot under the best condition of transfection of antisense oligonucleotide targeting bFGF, and the apoptosis in those cells was determined by flow cytometry. HepG2 cells were cultured in 24-well culture dish. The cultured cells were divided into 3 groups: group 1, the normal control group without any treatment; group 2, transfected with antisense oligonucleotide targeting bFGF; group 3, transfected with scrambled sequence targeting bFGF.

RESULTSThe results from confocal microscopy and Western blot showed an inhibition of expression of bFGF at different levels under the best condition of transfection with antisense oligonucleotide targeting bFGF. The treatment with antisense oligonucleotide of bFGF not only reduced the expression of bFGF revealed by confocal microscopy and Western blotting, but also increased the apoptosis in HepG 2 cells (P < 0. 01).

CONCLUSIONTreatment with antisense oligonucleotide of bFGF inhibits expression of bFGF protein and increase apoptosis. bFGF may take part in apoptosis regulation of hepatoma cells and may be used as a target in the treatment of hepatocellular carcinoma.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Oligonucleotides, Antisense ; pharmacology ; Transfection

OBJECTIVE: To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. METHODS: The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. RESULTS: The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. CONCLUSION Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.

A 67-year-old female patient with postoperative recurrence of stage Ⅳright renal cell carcinoma and multiple intracranial metastases was treated with sorafenib and sintilimab.Within 2 weeks,the patient had a fever and red spotted rash in facial,back,buttocks and limb.After 2 days,the fever completely relieved,but subcutaneous exudation appeared on the skin of both elbow joints,buttocks,and outer thighs,followed by gradual epidermal lysis and detachment with skin ulceration.After 4 days,the patient's epidermolysis area was greater than 30％of the body surface area.The patient was diagnosed with toxic epidermal necrolysis(TEN).The adverse reaction correlation was assessed by ALDEN SCORE sheet.The adverse reaction of TEN was"likely"caused by sorafenib and sintilimab.After withdrawal and treatment,the TEN was cured.This paper explores the correlation between the TEN and the combination use of sorafenib and sintilimab and the management.This paper will provide reference for the early diagnosis and correct treatment of TEN.

Activation and inflammation of microglial correlate with progressive neuronal apoptosis in neurodegenerative disorders such as Parkinson’ s disease (PD). γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, has recently been shown to play an inhibitory role in the immune system, but the mechanism is unclear. In this study, the results showed that LPS promoted the release of inflammatory factors in a dose-dependent manner compared with the control group (P<0. 01). Meanwhile, cell viability and cytotoxicity assays showed that the released inflammatory factors could induce the decline of SH-SY5Y cell viability. BV2 microglia cells were pretreated with GABA and Muscimol, a GABA

The study was aimed to investigate the incidences and risk factors of acute and chronic graft-versus-host diseases (GVHD) and to clarify their effects on relapse and survival of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 100 cases of allo-HSCT were retrospectively analyzed. The incidences and risk factors of aGVHD and cGVHD, relapse and survival were studied. The results showed that 31 cases developed aGVHD of II - IV grade (34.4%) and 14 cases developed aGVHD of III - IV grade (17.7%). HLA matched or mismatched did not show significant difference in the development of aGVHD of II - IV grade (p > 0.05). Previous occurrence of aGVHD was the risk factor for cGVHD (HR = 2.303, p = 0.088). The female was a favorable factor for cGVHD (HR = 0.401, p = 0.055). The relapse rate was lower in patients who developed cGVHD. The development of aGVHD of II - IV grade was the risk factor for overall survival (p < 0.05). The mortality of patients with aGVHD of III - IV grade and mortality of patients with aGVHD of 0 - I grade were 81.0% and 35.7% respectively, there was very significant difference between them (p = 0.000). In conclusion, till now GVHD and graft-versus-leukemia (GVL) effect can not be separated. The positive effect of GVL could be counteracted by GVHD-related mortality. It is necessary to prevent and control the development of severe aGVHD. The development of local cGVHD may be beneficial to the long-term disease-free survival of patients after allo-HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Graft vs Host Disease ; etiology ; mortality ; Hematopoietic Stem Cell Transplantation ; adverse effects ; mortality ; Humans ; Incidence ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVETo investigate the potential of siRNAs targeting sphingomyelin phosphodiesterase 1 (SMPD1) in protecting the oocytes from apoptosis, and explore new approaches to female fertility preservation.

METHODSChemically synthesized siRNA targeting SMPD1 were introduced into mouse oocytes retrieved by hyperstimulation, and the cell apoptosis was analyzed by comic assay 48 and 72 h later.

RESULTSIn the oocytes without any siRNA injection, oocyte DNA damage occurred after 24 h, and large amount of DNA fragments migrated from the cells 48 h later. In oocytes injected with siRNA003, DNA migration decreased significantly as compared with the control and the other two groups injected with siRNA001 and siRNA002 (P<0.01).

CONCLUSIONsiRNA targeting SMPD1 may protect the oocytes from apoptosis, and has the potential for use in future female fertility preservation.

Animals ; Apoptosis ; drug effects ; genetics ; Comet Assay ; Female ; Mice ; Oocytes ; cytology ; RNA Interference ; RNA, Small Interfering ; genetics ; Sphingomyelin Phosphodiesterase ; genetics ; physiology ; Transfection

OBJECTIVETo study the methylation level in the promoter of caspase 8 associated protein 2 (CASP8AP2) gene between samples at diagnosis and in complete remission, and to investigate its relationship with clinical features and prognosis in children with acute lymphoblastic leukemia (ALL).

METHODSDiagnostic DNA samples from 109 newly diagnosed children with ALL admitted from August 2007 to March 2010, and 94 ALL children in CR (complete remission) among them were collected. Bisulfite modification and MethyLight method established by our research team were used to determine the methylation level of the two key CpG sites (at -1189 and -1176) of the promoter of CASP8AP2 gene.

RESULTSThe average methylation level of the two CpG sites in newly diagnosted samples was higher than that in CR samples (71.1% ± 1.7% vs 64.2% ± 21.2%) (P = 0.008). Analysis with receiver operating characteristic (ROC) curve showed that the area under curve was 0.687 (P = 0.024), indicating that the methylation level of the two CpG sites was able to predict relapse efficiently to some extent, 76.9% was chosed as a cutoff value to divide the patients into high methylation group (49 patients) and low methylation group (60 patients). The incidence of relapse in high methylation group was higher than that in low methylation group (20.4% vs 6.7%) (P = 0.044), five year relapse free survival in high methylation group was also lower than that in low methylation group (Log rank, P = 0.033). Furthermore, high methylation at new diagnosis were correlated with high level of minimal residual disease (MRD) before consolidation therapy (P = 0.011). In the 34 children with MRD ≥ 10(-4) at the end of induction remission, the relapse rate of high methylation patients was significantly higher than that of low methylation patients (8/16 vs 3/18)(P = 0.038).

CONCLUSIONThe abnormal hypermethylation of the two CpG sites (at -1189 and -1176) of the promoter of the CASP8AP2 gene is possibly associated with leukemogenesis in childhood ALL. The treatment outcome is more poor in patients with hypermethylation than that in patients with low methylation. The combination of the methylation level of the two CpG sites and MRD level at the end induction remission is able to predict relapse more effectively.

Apoptosis Regulatory Proteins ; Calcium-Binding Proteins ; Child ; DNA Methylation ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Promoter Regions, Genetic ; Recurrence ; Remission Induction