Erdafitinib exerts the anticancer effect on urothelial carcinoma via induction of authophagy.

Erdafitinib has recently been approved for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC). The current study aimed to evaluate whether erdafitinib inhibits the proliferation in UC via inducing authophagy. Our data showed that erdafitinib demonstrated strong toxicity for the T24 and UMUC6 cell lines. Flow cytometry analysis showed that erdafitinib increased the proportion of G0/G1 phase in both T24 and UMUC6 cells. Additionally, Annexin V staining indicated that erdafitinib enhanced the apoptosis of UC cells. Meanwhile, the expression of apoptosis-related proteins was significantly elevated after treatment with erdafitinib. Transwell assay showed that erdafitinib significantly reduced T24 and UMUC6 cell migration and invasion. More importantly, western blot assay showed that erdafitinib induced the expression of autophagy-related proteins. Besides, GFP-LC3 transfection assay and electron microscopy examination showed that erdafitinib could partially diminish 3-methyladenine (3-MA) induced impairment of autophagy in UC cells. In summary, for the first time we showed novel data that erdafitinib inhibited UC cell malignant proliferation via inducing cell autophagy.

Diagnostic Value of Circulating miR-324 for Prostate Cancer.

BACKGROUND: To investigate the diagnostic value of serum miR-324 in patients with prostate cancer (PC). METHODS: Blood samples from 50 patients with prostate cancer, 30 patients with benign prostatic hyperplasia (BPH), and 20 healthy controls were collected and quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between serum miR-324 level and Gleason classification and TNM staging of prostate cancer was analyzed. ROC curve was used to analyze the value of miR-324 in early diagnosis of prostate cancer. RESULTS: The expression of miR-324 in prostate cancer group was significantly higher than that in the BPH group and normal control group (all p < 0.01). Serum miR-324 was associated with the Gleason score and tumor stage (all p < 0.01). Serum miR-324 was positively correlated with PSA (r = 0.673, p = 0.000); ROC curve analysis showed that the area under the ROC curve of miR-324 (all p < 0.01) (AUC) was 0.911 (95% CI: 0.855 - 0.966, p = 0.000). When the relative expression level of miR-324 was 3.35, the sensitivity, specificity, positive predictive value, and negative predictive values were 86.0%, 82.0%, 82.7%, and 85.4%, respectively. CONCLUSIONS: The increased expression of serum miR-324 in patients with prostate cancer may be a potential new biomarker for the diagnosis of prostate cancer, which is helpful for the differentiation between PC and BPH.

Hydrogen sulfide is endogenously generated in rat skeletal muscle and exerts a protective effect against oxidative stress / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) is endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle.</p><p><b>METHODS</b>The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer.</p><p><b>RESULTS</b>H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06 ± 0.43) nmol/mg; H2S production: (0.17 ± 0.06) nmol×min(-1)×mg(-1)). Gene and protein expressions of the three H2S producing enzymes were detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P < 0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P < 0.01).</p><p><b>CONCLUSION</b>H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.</p>

A modified Calgary syncope syndrome score in the differential diagnosis between cardiac syncope and vasovagal syncope / 中华儿科杂志

<p><b>OBJECTIVE</b>This study aimed at analyzing the usefulness of a modified Calgary Syncope Syndrome Score in the differential diagnosis between cardiac syncope (CS) and vasovagal syncope (VVS) in children through a large sample clinical study.</p><p><b>METHOD</b>Totally 189 children [112 males, 77 females, aged 2 - 18 yrs, mean age (12.4 ± 3.1) yrs] with CS and VVS who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2002 to April 2011 were included in the study. The diagnosis was analyzed by a modified Calgary Syncope Syndrome Score and receiver operating characteristic (ROC) curve was used to explore the predictive value of different Calgary Syncope Syndrome Scores in differential diagnosis between CS and VVS.</p><p><b>RESULT</b>There were significant differences in the score between CS [-5.00(-7, 1)] and VVS [1(-4, 6)] (P < 0.01). When the score was ≤ -2.5, the sensitivity and specificity of the differential diagnosis between CS and VVS were 95.4% and 67.7%, respectively. Since the modified Calgary Syncope Syndrome Score was integer number, CS should be considered when the score was less than -3.</p><p><b>CONCLUSION</b>The modified Calgary Syncope Syndrome Score might be used as an initial diagnostic method in differential diagnosis between CS and VVS, based on the history of the patients.</p>

Clinical analysis of orthostatic hypertension in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of orthostatic hypertension (OHT) in children.</p><p><b>METHOD</b>A total of 96 children with OHT who met the diagnostic criteria and clinical manifestations were recruited in the Department of Pediatrics, Peking University First Hospital. Age and sex distributions were observed. The duration of disease, the frequencies of symptoms and the predisposing factors were recorded. The hemodynamic changes from supine to up-right positions were also analyzed.</p><p><b>RESULT</b>There were 50 boys and 46 girls in the study group. The mean age was (11.8 ± 2.7) years. Thirty-two children were from 6 to 10 years old, accounting for 33.3% of all subjects, while 64 patients were from 11 to 17 years old, accounting for 66.7%. Durations of symptoms of OHT were less than 1 month in 22.9% children, from 1 month to 1 year in 51.1% children and longer than 1 year in 26.0% children. The most common clinical manifestations were syncope and dizziness. The incidence of them was 70.8% and 46.9%, respectively. Other clinical manifestations included transitional amaurosis, nausea and/or vomiting, pallor and so on. These clinical manifestations often occurred on position change (24.0%) and long-time standing (57.3%) in children. Other predisposing factors included exercise, emotion changes and fuggy environment. The baseline systolic and diastolic blood pressures were (103 ± 8) mm Hg (1 mm Hg = 0.133 kPa) and (59 ± 6) mm Hg, respectively, the up-right systolic and diastolic blood pressure at 3 min were (113 ± 8) mm Hg and (73 ± 6) mm Hg and the differences were significant (t = 27.674, P < 0.01; t = 17.936, P < 0.01). The baseline heart rate in supine position was (81 ± 11) bpm and the maximum heart rate in up-right position was (113 ± 12) bpm (t = 33.092, P < 0.01).</p><p><b>CONCLUSION</b>OHT is commonly seen in puberty of children. The chief complaints are syncope and dizziness. They were mostly induced by position change and long-time standing. Blood pressure was significantly increased from supine to up-right position.</p>

[V89L polymorphism of the testosterone 5-alpha-reductase II gene and prognostic factors of prostate cancer].

OBJECTIVE: To investigate the association of V89L polymorphism of the SRD5A2 gene with the prognostic factors of prostate cancer (PCa). METHODS: We identified the V89L polymorphic sites of the SRD5A2 gene after Rsa-1 restriction enzyme digestion, observed the distribution of V89L (VV, VL and LL) polymorphism in 112 PCa and 89 benign prostate hyperplasia (BPH) patients, and determined the association of V89L polymorphism with the age, free PSA (fPSA), total PSA (tPSA), fPSA/tPSA ratio, tumor stage and Gleason score of the PCa patients. RESULTS: No statistically significant differences were found in the V89L polymorphism-induced genetic risk frequencies between the PCa and BPH groups (chi2 = 3. 606, df = 2, P = 0. 165), nor any significant correlation between the genotypes of VV and VL + LL and the differences in the fPSA, tPSA, fPSA/tPSA ratio, tumor stage, Gleason score and age of the PCa patients. VV and VL + LL showed no obvious association with the prognostic factors of PCa. CONCLUSION: V89L polymorphism is not related with the prognosis of PCa, but may be indirectly associated with its risk.