AIM: To explore the protective effect of fluorofenidone (AKF-PD) on diethylnitrosamine-induced liver injury in rats and its inhibition of the TGF-β1/Smads pathway in hepatocytes. METHODS: Fifty-five male Sprague Dawley (SD) rats were randomly divided into three groups: model group (DEN group, n=20) were gavaged with DEN (10 mg/kg), 5 times for 14 weeks; control group (n=20) were gavaged with saline with the same volume of the model group; treatment group (DEN+AKF-PD Group, n=15), after 4 weeks of modeling, they were gavaged with AKF-PD (500 mg/kg) daily, and stopped at 14 weeks. At the end of experiment, the rats were killed by anesthesia and spinal dislocation. Masson staining was used to observe collagen deposition; primary hepatocytes were extracted and identified, and the levels of α-smooth muscle actin (α-SMA), TGF-β1, Smad3, and Smad7 mRNA, and the expression of Smad3 and Smad7 proteins in hepatocytes were detected. RESULTS: Compared with the control group, Masson staining showed that collagen deposition increased in the DEN group; AKF-PD treatment could significantly improve liver pathological damage and reduce collagen deposition. In addition, compared with the DEN group, the α-SMA, TGF-β1, and Smad3 mRNA levels of the AKF-PD group were significantly reduced, and the Smad7 mRNA level was increased. Moreover, AKF-PD treatment could dependably reduce the expression of Smad3 and increase Smad7. CONCLUSION: AKF-PD can significantly improve liver injury and fibrosis in rats caused by DEN. This effect may be related to the down-regulation of α-SMA, TGF-β1, and Smad3 mRNA levels in hepatocytes and the increase of Smad7 mRNA levels.

OBJECTIVE: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women. RESULTS: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M. CONCLUSION Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.
China ; Dystrophin/genetics* ; Exons ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation. METHODS: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEase RESULTS: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele. CONCLUSION FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.
Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pregnancy ; Prenatal Diagnosis

Hypoxia-inducible factor-α ( HIF-1α) is a regulatory protein in human body, which is closely related to the occurrence and development of cervical cancer. HIF-1α is an important factor affecting the radiosensitivity of cervical cancer. Many genes and proteins are involved in the regulation of radiosensitivity by HIF-1α. These genes and proteins are directly or indirectly affecting the efficacy of radiotherapy for cervical cancer. A lot of research is under way. This review summarizes the recent advances in genes and proteins associated with HIF-1α affecting radiosensitivity in cervical cancer.

Epigenetics is a researching hot topic of worldwide now.Increasing evidence shows that the pathogenesis of human diseases is not only influenced by the abnormalities of genetic factors but also by epigenetic mechanisms.Recent technological advances in epigenomic profiling has led to further understanding of the role epigenetic factors played in development,inflammation,aging,immunity,angiogenesis,tumorigenesis,and stem cell biology.The researchers in ophthalmology should pay close attention to the current research of major epigenetic mechanisms and their involvement in human diseases,especially ocular diseases.Moreover,the potential application of epigenetic drugs in the treatment of common human diseases also should be understood.Finally,the challenges and future perspectives underlying epigenetic research are discussed in this editorial paper.

Epigenetics has become a hot topic in biomedical research in last a few years.Epigenetics refers to as epigenome,and it is interpreted as epigenetic changes (DNA methylation,histone modifications and non-coding RNAs such as microRNAs) in the regulation of genes expression on chromatin-based pathways rather than a single gene.Epigenetic factors such as DNA methylation,histone modification and miRNA serve as an interface for environmental stimuli and interacts each other to regulate gene expression and control phenotypes of cell.All of those epigenetic factors are essential in the keeping homeostasis of human body and contribute to many biologic conditions.In addition,the application of epigenetic drugs has been come into clinical trials especially in the treatment of cancers,therefore the understanding the mechanism of epigenetics in the development of human diseases and the therapeutic potential of epigenetic regulators in the treatment of human disease will bring us into the epigenetics era in biomedical research.

Objective To study the clinical efficacy and operative skill of multi-endoscopic technique in treatment of post-traumatic urethrostenosis in male patients.Methods A retrospective analysis was done on clinical data of 47 male patients with post-traumatic urethrostenosis treated with direct visional incision urethrotomy combined with transurethral resection of scar tissue and ureteroscopic incision.There were 29 patients with anterior urethral strictures and 18 with posterior urethral strictures.Results Of all,43 patients underwent successful endoscopic surgeries at the first time but one underwent secondary surgery because of unsuccessful endoscopic incision.These patients achieved satisfactory results without urinary incontinence,fistula or reoperation.The left three patients underwent open surgeries because of unsuccessful endoscopic incision,in which one patient could micturate at maximal flow rate of 9-12 ml/s,without therapeutic urethral dilation,one could micturate under regular therapeutic dilation and the other one could not micturate.Conclusions With the advantages of safety,high success rate and good long-term efficiency,multi-endoscopic technique can be used as an initial treatment for male patients with post-traumatic urethrostenosis and is worthy to be popularized.

Objective To assess the clinical value of intravesical prostatic protrusion (IPP) measured by transabdominal uhrasonography in judgement of benign prostatic obstruction (BPO). Methods According to pressure-flow study, 109 patients with benign prostatic hyperplasia were di-vided into 3 groups (non-obstruction, equivocal obstruction and obstruction). IPP was measured by transabdominal ultrasonography in all patients. The difference of IPP between different groups was studied and the correlation between IPP and the parameters reflecting BPO was analyzed. Results IPP value of the non-obstruction group, equivocal obstruction group and obstruction group was 2.7 ±1.2 mm, 2.9±1.4 mm and 15.4±6.5 mm. There was significant difference in IPP between the non-obstruction group, equivocal obstruction group and obstruction group (P<0.01). IPP was correlated with the parameters including Pdet. Qbeg, Pdet. Qmax, Pdet. Qend, Qmax and A-G number, Spearman's ratio was 0. 628, 0. 714, 0. 591, -0. 450 and 0. 729(P<0.01), respectively. The sensi-tivity and specificity of judging BPO were 89.9% and 97.5% if the cut-off was IPP≥10 mm. Con-clasion IPP measured by transabdominal ultrasonography could be a convenient and accurate method in diagnosis of BPO.

Objective To investigate the differentiation of CD4+T helper cell in expressed prostatic secretions(EPS)in type Ⅲ prostatitis. Methods Seventy-six patients were studied,aged from 18 to 47(average 31.8).All patients presented with typical clinical symptoms for over 3 months.Cases were classified as type Ⅲ A(47 cases),type Ⅲ B(29 cases)and control group(16 cases)according to NIH classification system.Type Ⅲ A was also divided into group Ⅲ A1 with 26 cases(mild inflammation)and group Ⅲ A2 with 21 cases(severe inflammation).Th1 cytokine IFN-γ,Th2 cytokines IL-4 in EPS were detected by double antibody sandwich ELISA,and IFN-γ/IL-4 was determined.Results Compared with group control,IFN-γ in group Ⅲ A and Ⅲ B were significantly up regulated (134.78±43.67 pg/ml,109.82±30.09 pg/ml,P＜0.05),while IFN-γ level in group Ⅲ A was higher than in group Ⅲ B(P＜0.05).IL-4 in groupⅢ A was not changed(51.99±20.59 pg/ml,P＞0.05).IL-4 in group ⅢB was higher(76.40±17.99 pg/ml,P＜0.05).IFN-γ/IL-4 in group ⅢA was elevated significantly(2.94±1.12,P＜0.05),while IFN-γ/IL-4 in group ⅢB was not changed(1.49±0.48,P＞0.05).IFN-γ/IL-4 in group Ⅲ A2 was higher than in groupⅢA1 significantly(3.67±0.82vs 2.34±0.97,P＜0.05). Conclusions Th1 eell differentiation took the dominance in type Ⅲ A prostatitis.Th1/Th2 equilibrium was shifted to Th1.It is probably one of the pathogenies that Th1 dominant differentiation leads to local inflammation in prostate of type Ⅲ A prostatitis.

Abstract Objective To investigate the expression of interleukin 2 receptor alpha (IL-2Rα) in human retinal pigment epithelial cell (RPE) and the effect of IL-2 on RPE proliferation. Methods Passage 2 -4 human fetal RPE cells were used in the experiment. RT-PCR was performed with the specific primer for IL-2Rα. IL-2 binding was assayed by fluorescence-activated cell sorting. Immunofluorescent staining was applied to identify the receptor expression using anti-CD25. The effect of recombinant IL-2 on RPE cell proliferation was determined by3H uptake. Results RPE cells expressed IL-2Rα mRNA. The expression of IL-2 receptor α was also revealed by immunofluorescent staining and IL-2 binding. IL-2 induced cell proliferation at the higher concentrations of IL-2 ( P＜0.05 ). Conclusion Cultured human RPE cells express IL-2α receptor. Recombinant IL-2 enhances RPE cell proliferation.