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

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

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

OBJECTIVEFace-to-face interview (FTFI) and polling booth survey (PBS) were applied to compare the high risk behavior among HIV-positive clients of female sex workers (CFSWs).

METHODSThis study was conducted in antiretroviral therapy (ART) out-patients centers in Hengyang city, where clients who had been informed on their HIV-positive status for 6 months or longer were recruited. FTFI was first used to tackle on 8 sensitive questions related to sexual behavior, followed by PBS to poke on the same questions. Results from FTFI and PBS were then compared.

RESULTSCompared with FIFI, results in the PBS showed higher proportion of participants who reported "having had history of sexually transmitted diseases before knowing that they were infected with HIV" (40.6% vs. 24.2%) but lower proportions on "frequency of having sex with regular sexual partner less than 4 times per month" and "using condoms consistently with regular sexual partners in past 6 months (44.4% vs. 63.0%)". There were no significant differences in the remaining 5 questions shown in the results from the two methods.

CONCLUSIONHIV-positive CFSWs continued to practice unsafe sexual behaviors after knowing their HIV related status. Compared with FTFI, PBS seemed to have revealed higher proportion of unsafe sex behaviors, so as to generated more reliable data. While comparing with PBS, the traditional FTFI might have underestimated the risk behaviors among those HIV-positive CFSWs.

Condoms ; utilization ; Data Collection ; methods ; Female ; HIV Seropositivity ; Humans ; Male ; Reproducibility of Results ; Risk-Taking ; Sex Work ; Sex Workers ; Sexual Behavior ; psychology ; statistics & numerical data ; Sexual Partners ; Sexually Transmitted Diseases ; epidemiology ; Unsafe Sex ; psychology