Objective· To assess the efficacy of abiraterone acetate (AA) plus prednisone treating metastatic castration-resistant prostate cancer (mCRPC) patients and analyze the prognostic factors for this treatment. Methods · The medical history of 112 patients with mCRPC treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, including 70 patients in the chemotherapy-na?ve setting and 42 in the post-chemotherapy setting, were retrospectively reviewed. Coprimary end points were prostate specific antigen progression-free survival (PSA PFS), radiographic PFS (rPFS) and overall survival (OS). Univariable and multivariable Cox analyses were performed to determine prognostic factors that were associated with PSA PFS, rPFS and OS. Results · At a median follow-up of 20.2 months, 59 (52.7%) patients had died. The median PSA PFS, rPFS and OS were 8.9 (7.8~10.0) months, 9.7 (9.0~10.4) months, and 22.2 (20.3~24.1) months, respectively. In multivariate analysis, previous chemotherapy, neutrophil lymphocyte ratio(≥3 vs<3),serum lactate dehydrogenase level(≥196 U/L vs<196 U/L)and ECOG PS(≤?1 vs 2)were independent predictors for PSA PFS and rPFS,and previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS. Conclusion·These results further support the favourable profile of AA plus prednisone in patients with mCRPC in China.Previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS.

Objective·To screen NPHS2 mutations in adult focal segmental glomerulosclerosis(FSGS)patients based on a large Chinese FSGS cohort. Methods · All patients were biopsy determined FSGS by the Department of Nephrology at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. FSGS secondary to systemic disease and other hereditary kidney disease were excluded. After extraction of genomic DNA of peripheral blood,NPHS2 was screened by directly sequencing the exon/intron junction or high-throughput sequencing,including whole exon sequencing and Panel sequencing, and then verified by Sanger sequencing. One hundred healthy controls were enrolled to validate candidate mutations. Results · Two hundred and four FSGS patients were enrolled,including 52 familial(25.5%) and 152 sporadic patients(74.5%),of which steroid-resistant FSGS patients accounted for 30.3%(46/152).By sequencing NPHS2 in all patients of the cohort(Sanger sequencing in 61 patients and high-throughput sequencing in 143 patients), 2 novel conserved mutations were identified, one homozygous mutation in sporadic steroid-resistant FSGS, p.N199I and one heterozygous mutation in familial FSGS, p.L321fx346. Both of them were not detected in 100 healthy controls. These two variants were predicted to be damaging by Polyphen,SIFT and Mutation Taster.Totally,the mutation rate of NPHS2 in the FSGS cohort was 1%. Conclusion·Since the overall frequency of NPHS2 mutations is considerably low in Chinese adult-onset FSGS,NPHS2 is not the main disease-causing gene of this group of people.

Objective· To investigate the value of three-dimensional spin-lattice relaxation (T1ρ) magnetic resonance imaging (MRI) for liver fibrosis detection and staging and compare with two-dimentional real-time shear wave elastography (SWE). Methods · Twenty-nine rabbit models of CCl4-induced liver fibrosis were established and six untreated rabbits served as controls. T1ρ MRI and two-dimentional real-time SWE examinations were performed at 2, 4, 6, 8, 10 and 12 weeks, respectively. T1ρ values and liver stiffness (LS) values were measured. Fibrosis was staged according to the METAVIR scoring system. Correlation test was performed among T1ρ values, LS values and fibrosis staging. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic performance of T1ρ and SWE in detection of fibrosis. Results · There was a moderate positive correlation between fibrosis staging and T1ρ values (r=0.566, P=0.000), and a significantly positive correlation between fibrosis staging and LS values (r=0.726, P=0.003).Areas under ROC were 0.861 for SWE and 0.856 for T1ρ(P=0.940),0.906 for SWE and 0.849 for T1ρ(P=0.414),0.870 for SWE and 0.799 for T1ρ (P=0.422), and 0.846 for SWE and 0.692 for T1ρ (P=0.137), when diagnosing liver fibrosis with ≥?F1, ≥?F2, ≥?F3 and F4 stage, respectively. Conclusion · T1ρ imaging has potential for liver fibrosis detection and staging with good diagnostic capability similar to that of SWE.

Objective· To prepare nanocarriers capable of improving the immunogenicity of cholesteryl ester transfer protein (CETP) hapten. Methods · Prepare CETP polypeptide modified by thiol in Fmoc, then Sulfo-SMCC were used to prepare CETP peptide-ovalbumin (OVA) nanoparticle and CETP peptide - OVA molecule conjugates in a two-step reaction scheme. The particle size and zeta potential of nanovaccine were determined and the morphology was observed. New Zealand White rabbits were vaccinated by subcutaneous injection of vaccine and serum collected from rabbits was detected by ELISA assay for the analysis of antibodies, high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol (LDL-C). The rabbits were randomly allocated to the PBS group (n=3), traditional vaccine group (n=3), and nanovaccine group (n=3). Results · Nanovaccine targeting CETP were successfully synthesized, with about 70 nm in size and about -8.81 mV in zeta potential, and possessed homogeneous spherical shape under transmission electron microscopy. Compared with traditional vaccine group, rabbits in nanovaccine group got higher antibodies. Conclusion · Nanovaccine improve immunogenicity of CETP haptens, and stimulate experiment rabbits to produce higher antibodies.

Objective· To observe real-time changes of calcium concentration ([Ca2+]i) exposure to bilirubin in synaptosomes isolated from brainstem nucleus of rats. Methods · Forty P7-14 SD rats were randomly assigned to three groups: control group, bilirubin group (with levels of 0.1, 1 and 10 μmol/L) and bulirubin plus glycoursodeoxycholic acid (GUDCA) group. The synaptosomes were purified from brainstem nucleus by sucrose density gradient centrifugation. After loading OG-BAPTA in synaptosomes, two dimensional image of intracellular calcium and analysis of fluorescence intensity were achieved by Confocal laser scanning microscopy. Results · Synaptosomes with well biological activity were obtained from brainstem of the SD rats. In the control group, a progressive increase in fluorescent intensity of [Ca2+]I was detected. In the bilirubin group, acuter increases in fluorescent intensity were observed in all levels of bilirubin, with a manner of both concentration and time-dependent (P<0.05). Fluorescent intensity of [Ca2+]I was reduced in the present of GUDCA, which was not significant compared with the control group (P=0.656). However, GUDCA could abate the increase of fluorescent intensity of [Ca2+]I induced by bilirubin exposure, of which showing significant decrease in 10 μmol/L bilirubin exposure (P=0.000). Conclusion · Bilirubin could induce calcium overload in synaptosomes. GUDCA could abate bilirubin-induced calcium overload in synaptosomes, possibly explaining its protection effect of neurons from bilirubin neurotoxicity.

Currently, exploring the "World-class" disciplinary construction is a vital strategy in China. Since 2015, Shanghai Jiao Tong University School of Medicine started the project of establishing two distinguish teams—the academic clinicians and clinical investigators ("Two-hundred Talent" team), to fuel the development of clinical research. After two years of practice, both advantages and bottlenecks were found. The advantage contains: increasing selection rate among talent projects, increasing influential output, elevating capacity in clinical research. The bottlenecks contain: unbalanced disciplinary development, poor awareness of the importance of clinical research, lack of relevant supporting policies. In order to improve the quality of the clinical research and the two talent clinical research teams, institutional innovation, personalized supporting system, establishment of clinical research center, training of clinical research nurses are essential.

Diabetes mellitus is a common metabolic disease and poses serious threat to human health. Diabetic complications are the major causes of both morality and disability. In recent years, studies show that the glucose fluctuation plays an important role in the development of chronic diabetic complications. As a new discipline to identify the overall metabolic changes of living organisms, metabolomics provides new insights into the study of diabetes and diabetic complications. In this paper, the recent studies on the development of chronic diabetic complications and blood glucose fluctuation in the field of metabolomics were reviewed.

Based on the dominant fluctuation rates, the speech information in temporal domain could be divided into temporal envelope, periodic fluctuation information and temporal fine structure. Temporal envelope cues are essential for speech recognition, which could be transmitted to cochlear implanters by cochlear imlpants. The roles of temporal envelope cues from various frequency regions in speech recognition are diverse. Influenced by the testing materials, research methods, listening backgrounds and the parameters used to extract temporal envelope, the relative weights of temporal envelope across frequency regions would change accordingly. The research methods as well as their advantages or disadvantages and research results of relative weights of temporal envelope cues in different frequency regions are reviewed, and the possible reasons why the relative weights of temporal envelope cues in different frequency regions for non-tonal language and tonal language were different were discussed simply.

Adipocyte plasma membrane associated protein (APMAP) is a novel integral membrane protein, widely expressed in many organizations in humans. It promotes the differentiation of preadipocytes to mature adipocytes, so as to maintain normal physiological metabolism function in adipocytes, and plays a major role in adipocytes differentiation. Nowadays, some progress has been made in its role of inflammation and consequently in pathogenesis of gestational diabetes mellitus and other diseases. This paper gives a brief review about the structure and function of APMAP and sums up progress of the current studies.

Objective· To correct the false-positive categorization of the rare and benign variants by re-sequencing of the recessive deafness genes in carriers. Methods · Heterozygous carriers of known causative mutations in recessive deafness genes were identified from normal hearing relatives of the deaf probands.Targeted next-generation sequencing was performed in those carriers to identify additional variants in trans,which was presumed to be benign. Results · A total of 30 normal-hearing carriers of heterozygous and known pathogenic mutations were identified. By targeted next-generation sequencing of corresponding genes,32 non-synonymous variants in trans were identified,which were categorized to benign mutations under the recessive and full-penetrant mode.Among those variants p.A434T in SLC26A4,p.R266Q in LOXHD1,p.K96Q in MYO15A,p.T123N in GJB2 and pV1299I in CDH23 were five rare variants with minor allele frequency of less than 0.005.Some of the 5 variants were predicted to be pathogenic by prediction programs including Polyphen-2, PROVEAN, SIFT and MutationTaster, or documented to be pathogenic by Deafness Variation Database or Human Genome Mutation Database. Conclusion · Re-sequencing of the recessive deafness genes in carriers may efficiently correct the false-positive categorization of some rare and benign variants to improve the accuracy and efficiency of the next-generation sequencing in diagnosis of monogenic recessive hereditary disorders.