LINC00106/RPS19BP1/p53 axis promotes the proliferation and migration of human prostate cancer cells.

Background: Prostate cancer (PCa) is among the most prevalent cancers in males with high biochemical recurrence risk. LINC00106 contributes to the carcinogenesis of Hepatocellular carcinoma (HCC). However, it is unclear how it affects PCa advancement. Here, we studied LINC00106's effects on PCa cells' ability to proliferate, invade, and metastasize. Methods: The data of LINC00106 from The Cancer Genome Atlas (TCGA) in human PCa tissues were analyzed using TANRIC and survival analysis. In order to determine the expression levels of genes and proteins, we also performed reverse transcription-quantitative PCR and western blot analysis. The migration, invasion, colony formation, and proliferation (CCK-8) of PCa cells with LINC00106 knockdown were investigated. The impact of LINC00106 on cell proliferation and invasion was also analyzed in mice. LncRNA prediction software catRAPID omics v2.1 (catRAPID omics v2.0 (tartaglialab.com)) was used to predict proteins that might interact with LINC00106. The interactions were verified via RNA immunoprecipitation and RNA pull-down assays and finally, the interaction between LINC00106 and its target protein and the p53 signaling pathway was studied using a dual-luciferase reporter assay. Results: In PCa, LINC00106 was over-expressed in comparison to normal tissues, and it was linked to an unfavorableprognosis. In vitro and in vivo analyses showed that downregulating LINC00106 decreased PCa cells'ability to proliferate and migrate. A common regulatory axis generated by LINC00106 and RPS19BP1 prevents p53 activity. Conclusion: Our experimental data indicate that LINC00106 functions as an oncogene in the onset of PCa, and the LINC00106/RPS19BP1/P53 axis canserve as a novel therapeutic target for PCa treatment.

Design of an Efficient CNN-based Cough Detection System on Lightweight FPGA.

Precisely and automatically detecting the cough sound is of vital clinical importance. Nevertheless, due to privacy protection considerations, transmitting the raw audio data to the cloud is not permitted, and therefore there is a great demand for an efficient, accurate, and low-cost solution at the edge device. To address this challenge, we propose a semi-custom software-hardware co-design methodology to help build the cough detection system. Specifically, we first design a scalable and compact convolutional neural network (CNN) structure that generates many network instances. Second, we develop a dedicated hardware accelerator to perform the inference computation efficiently, and then we find the optimal network instance by applying network design space exploration. Finally, we compile the optimal network and let it run on the hardware accelerator. The experimental results demonstrate that our model achieves 88.8% classification accuracy, 91.2% sensitivity, 86.5% specificity, and 86.5% precision, while the computation complexity is only 1.09M multiply-accumulation (MAC). Additionally, when implemented on a lightweight field programmable gate array (FPGA), the complete cough detection system only occupies 7.9K lookup tables (LUTs), 12.9K flip-flops (FFs), and 41 digital signal processing (DSP) slices, providing 8.3 GOP/s actual inference throughput and total power dissipation of 0.93 W. This framework meets the needs of partial application and can be easily extended or integrated into other healthcare applications.

Synergistic Effect of 3-Bromopyruvate in Combination with Rapamycin Impacted Neuroblastoma Metabolism by Inhibiting Autophagy.

BACKGROUND: Alterations in the cell metabolism, such as enhanced aerobic glycolysis, have been identified as a prominent hallmark of cancer cells. 3-Bromopyruvate (3-BrPA) is a proverbial hexokinase (HK)-II inhibitor, which can inhibit cancer cell energy metabolism. Rapamycin is a new type macrocyclic lactone, which can inhibit the serine/threonine protein kinase mTOR. In order to comprehend the influence of 3-BrPA on autophagy activity in vitro, we conducted a series of experiments using different human neuroblastoma (NB) cell lines. MATERIALS AND METHODS: The human NB cell lines were exposed to 3-BrPA and/or rapamycin, and the proliferation activity of the cells was detected by Cell Counting Kit-8 (CCK-8) assay. The mRNA expression of the cells treated with 3-BrPA and/or rapamycin was analyzed by quantitative real-time polymerase chain reaction (QPCR) assay. The protein expression of the cells was analyzed by Western Blotting (WB) assay. The effects of 3-BrPA and/or rapamycin treatment on cell cycle and cell apoptosis were analyzed by flow cytometry assay. Meanwhile, the cellular glucose absorption rate, lactate secretion rate and ATP content were also analyzed through the relevant metabolic analysis kits. RESULTS: Our results showed that 3-BrPA can induce growth inhibition in a dose-dependent pattern by cell apoptosis. 3-BrPA combined with rapamycin played a synergistic suppression role in NB cells, affected the cell apoptosis, cell cycle and the metabolic pathway. Up-regulated LC3-II accumulation was conscious in NB cells incubated with 3-BrPA and rapamycin. Rapamycin individually discourages the mTOR signaling pathway, while combined with 3-BrPA can enhance this phenomenon and influence cell metabolism of the NB cells. CONCLUSION: The results suggested that 3-BrPA combined with rapamycin could induce cell apoptosis in NB cells by inhibiting mTOR activity. In conclusion, our research proposed that the dual inhibitory effect of the mTOR signaling pathway and the glycolytic activity may indicate a valid therapeutic tactic for NB chemoprevention.

Isolation and characteristics of multi-drug resistant Streptococcus porcinus from the vaginal secretions of sow with endometritis.

BACKGROUND: Sow endometritis is a common disease in pig breeding farms after artificial insemination, which leads to gray-green vaginal secretions and decreased conception rates. It is important to perform an etiologic diagnosis for effective treatments and control of diseases. The aim of this study was to carry out a pathogenic detection in five specimens of vaginal secretions collected from sick pigs with endometritis, implement identification of the pathogens by phenotypic detection and 16 s rDNA sequence and phylogeny analysis, and determinate antibiotic susceptibility of the isolates. RESULTS: A Streptococcus strain was isolated and identified from all of the five specimens. The isolate was positive for Voges-Proskauer (V-P) and for the hydrolysis of arginine, esculin and myelin-associated glycoprotein (MAG). Acid formation was observed for sorbitol, mushroom sugar, sucrose, and glucose. The 16S rDNA sequence of the isolate possessed 99.93% similarity to that of Streptococcus porcinus. The phylogenetic analysis of 16S rDNA sequence showed that the isolate belonged to the same clade as the S. porcinus strains from humans, pigs, and other animals. The isolate exhibited multi-drug resistance to aminoglycosides, quinolones, macrolides and tetracyclines except being sensitive to some ß- lactams such as penicillin G, cephalothin, cefazolin, cephradine and cefuroxime. CONCLUSIONS: A S. porcinus isolate with multi-drug resistance was identified from vaginal secretions of sows with endometritis in one pig breeding farm, which suggests that the sow endometritis was caused by S. porcinus infection during artificial insemination. This study indicates that sensitive antibiotics such as penicillin G or some cephalosporins could be used for treatment of the diseases. In addition, the study hints that bacterial multi-drug resistance is a tough problem for disease treatment in pig farms.

[The correlation between NPHS2 polymorphism and IgA nephropathy in northern Chinese patients].

OBJECTIVE: To examine the polymorphism in NPHS2 gene of IgA nephropathy in northern Chinese patients and to investigate the possible association of the NPHS2 polymorphism with the development of IgA nephropathy, as well as its clinical and histologic manifestations. METHODS: The polymorphism of NPHS2 was analyzed by direct DNA sequencing in 32 northern Chinese patients with IgA nephropathy (16 with heavy proteinuria and 16 with isolated hematuria). According to preliminary results, a total of 537 IgA nephropathy patients were genotyped for the NPHS2 C357T polymorphism by PCR combined with restriction fragment length polymorphism (PCR-RFLP). We collected clinical and histologic manifestations for gene analysis in patients with IgA nephropathy, such as age, sex, urine protein excretion and so on. RESULTS: Eight NPHS2 polymorphisms (-931A > T, -601C > T, 19G > T, 171A > G, 357C > T, IVS3-21C > T, 1023C > T and 1107A > G) were identified. The preliminary results of gene sequencing showed that the frequency of 357T allele in nephrotic syndrome group was obviously lower than isolated hematuria group (0.038 vs 0.125, P < 0.05). In 537 IgA nephropathy patients with clinical and histologic data, the average urinary protein excretion in the patients with the 357CT/TT genotype was less (P = 0.023). The incidence of urinary protein of more than 3.5 g/d was significantly lower in patients with T allele and TT/CT genotype, respectively (P = 0.017 and 0.011). The logistic regression analysis indicated that, even after adjusting for the effect of hypertension and age of patients, the CT/TT genotype of NPHS2 C357T was an independent protective factor for the urinary protein excretion more than 3.5 g/d (P = 0.012, OR = 0.485, 95%CI 0.275 - 0.84). CONCLUSIONS: Eight NPHS2 polymorphisms were identified in northern Chinese IgA nephropathy patients. The frequencies of NPHS2 T allele and TT/CT genotype were the protective factors for urinary protein, especially with that of more than 3.5 g/d.

[The clinical and pathological subtypes of Castleman's disease and their relationship with complications: a large series analysis from a single center].

OBJECTIVES: To investigate the clinical and pathological subtypes of Castleman's disease (CD) and their relationship with complications. METHODS: The clinical complications of 53 patients with CD and the relationship of these complications with clinical and pathological subtypes were analyzed retrospectively. RESULTS: Among 53 CD patients, 32 (60.4%) were classified as uni-centric type and 21 (39.6%) multicentric type. Histopathological examination showed that 37 cases (69.8%) were hyaline vascular variants (HV), 9 (17.0%) plasmacytic variants (PC), and 7 (13.2%) mixed cellular variants (Mix). Complications were identified in 32 (60.4%) patients, including the involvements of skin, internal organs and hematopoietic system. Some complications were closely associated with the clinical subtype of CD: the majority of complications in the 32 uni-centric CDs were paraneoplastic pemphigus (PNP) and bronchiolitis obliterans (BO), and those in 21 multi-centric CDs were the involvements of kidney and hematopoietic system. The complications were different among the three kinds of histopathological subtypes: PNP and BO were the predominant complications of HV variants, while the internal organ and hematopoietic system involvements were those of PC and Mix variants. The clinical and histopathological classification of CD patients with PNP were different obviously from other subtypes of CDs. In Kaplan-Meier survival analysis, the survival rate of those with complications was significantly lower than those without complication (P = 0.028). CONCLUSION: The clinical complications of CDs are related to their clinical and histopathological subtypes. CD patients with PNP should be considered as a unique entity to tailor the therapy. The presence of clinical complications is an independent prognostic factor in CD patients.

[Association of NPHS1 gene polymorphism with IgA nephropathy].

OBJECTIVE: To investigate the association of the polymorphism of NPHS1, coding gene of nephrin, with the degree of proteinuria, renal function, and prognosis of IgA nephropathy (IgAN) in patients in north China. METHODS: Peripheral blood samples were collected from 532 patients with IgAN confirmed by biopsy, 285 males and 230 females, aged (31+/-11). Genomic DNA was isolated from the peripheral blood leucocytes. Polymorphism of the exon G349A of NPHS1 was detected by polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP). 138 patients were followed up for 4-99 months. The correlation between the NPHS1 polymorphism and renal function at the time of renal biopsy, and that between NPHS1 polymorphism and the prognosis were analyzed. RESULTS: The frequency of the genotype with the allele G (AG/GG) in the patients with the estimated glomerular filtration rate (eGFR)<60 mlxmin(-1)x(1.73 m2)(-1) was significantly higher than that of the patients with the eGFR>60 ml.min(-1)x(1.73 m2)(-1) (P=0.008). Even after adjusting for the effects of proteinuria, hypertension, and age, AG/GG genotype was an independent risk factor of the exacerbation of renal damage at the time of diagnosis (P=0.011), and GG genotype was an independent risk factor of the prognosis (P<0.001). CONCLUSION: G allele and AG/GG genotype are associated with the severity of renal function at the time of diagnosis the GG genotype is associated with the prognosis of IgAN patients.

[Approaches to detect the gene mutations in autosomal recessive Alport's syndrome: analysis of a family].

OBJECTIVE: To explore the gene diagnostic method for autosomal recessive Alport syndrome (AR-AS). METHODS: Genomic DNA was extracted from the peripheral leukocytes of the proband of an AR-AS family. All the exons of COL4A3 and COL4A4 introns were amplified by PCR, and then the PCR products were sequenced by direct sequencing. Meanwhile, the mRNA of the coding region of type IV collagen alpha3 and alpha4 chain was extracted from the PBL and EB virus transfected cell and analyzed by using RT-PCR and sequencing to conform the genomic DNA analysis results. RESULTS: PCR-sequencing analysis identified two novel COL4A3 mutations. One was a 5' donor splice site mutation (c. 3418 + 1 G to A) in exon 39, leading to the deletion of exon 39 in mRNA level by RT-PCR analysis. The other was a deletion mutation of 9 bp at exon 25 (c. 1729-1737 del9). CONCLUSION: Both genomic-DNA-PCR-sequencing and mRNA-RT-PCR-sequencing methods can be carried out to detect the pathogenic mutations. In particular, mRNA-based approach can identify the changes in transcript level, therefore it is better than the genomic DNA-based method.

[Clinical analysis of 8 cases with cryoglobulinemic glomerulonephritis].

OBJECTIVE: To study the clinical and pathological features of cryoglobulinemic glomerulonephritis. METHODS: The clinical and pathologic data from 8 cases with cryoglobulinemic glomerulonephritis, which were referred to Peking University First Hospital from 2002 to 2006, were reviewed. RESULTS: There were seven males and one female, with an average age of 48.6 +/- 13.6 years. Most of the patients were referred as primary glomerulonephritis and the mean interval from onset to diagnosis was 19 months. 5 cases showed positive result with blood cryoglobulin test as inferred from renal biopsy. At the time of diagnosis 5 cases (5/8) showed nephritic syndrome and 3 (3/8) progression of renal failure. Fifty percent of the patients died in 6 months during the two-year follow-up. The main pathological pattern was membranoproliferative glomerulonephritis (7/8) with glomerular subendothelial deposits and intraluminal thrombi. Four cases (4/8) were associated with lymphoproliferative disorders and only one case with HCV infection. CONCLUSION: Cryoglobulinemic glomerulonephritis was not rare. Most of the patients were diagnosed at a late stage with a poor prognosis in China. It should draw a special attention of the clinicians.

[Angiolymphoid hyperplasia with eosinophilia involving the kidney: a report of three cases with literature review].

OBJECTIVE: To report the clinical and pathological characteristics of renal involvement in angiolymphoid hyperplasia with eosinophilia (ALHE). METHODS: Three cases of ALHE with renal involvement were diagnosed in our hospital. Routine pathological examination and immunohistochemical study of CD(31), CD(34) and F(8) of lymph node and renal biopsy specimens were performed and the clinical and pathological features were analysed. RESULTS: All three patients were male. Subcutaneous mass in the neck and head region accompanied with proteinuria and renal function impairment were the clinical characteristics of the three patients. Peripheral blood eosinophilia with elevated IgE level was detected in all the 3 patients. The level of serum immunoglobulins and complements were abnormal in 2 of them. They were sensitive to corticosteroid and cyclophosphamide therapy, but one case showed a recurrence after the withdrawal of immunosuppressive agents. Histopathological examination of lymph node and renal tissue showed a prominent proliferation of small vessels lined with hypertrophic epitheloid endothelial cells, which led to a narrowed or even closed vascular lumen. Diffuse infiltration of eosinophils, lymphocytes and plasma cells was identified around the hyperplastic vessels. With immunohistochemical study, CD(31), CD(34) and F(8) were positive in hyperplastic endothelial cells. Renal lesions were mainly distributed in tubulointerstitial area, while one case exhibited membranous nephropathy (stage I). CONCLUSION: ALHE with renal involvement is not rare in our country. The clinical and pathological characteristics of ALHE suggested that it might belong to an entity of angiolymphoid hyperplasia associated with allergic response.

[Variable number of tandem repeats polymorphism of MUC20 is associated with the progression of IgA nephropathy].

OBJECTIVE: The MUC20 gene is a novel up-regulated gene that was identified in renal tissues of patients with IgA nephropathy (IgAN) by restriction endonucleolytic analysis of differentially expressed sequences. The variable number of tandem repeats (VNTR) polymorphism of MUC20 was detected in different cell lines. In this study we determined the distribution of MUC20 VNTR polymorphism in the healthy population, and the association between the MUC20 VNTR polymorphism and the pathogenesis or progression of IgAN. METHODS: 282 healthy and 503 proved IgAN patients by biopsy were involved in this investigation. 113 patients had been followed-up for 3.5 +/- 1.5 years. Genomic DNAs were extracted from peripheral blood leucocytes. MUC20 VNTR polymorphism was detected by PCR amplification and several representational PCR products were confirmed by sequencing. The MUC20 genes were divided into small alleles (repeat times 3) according to the repeat times of MUC20 VNTR. These patients were classified into group SS, SL and LL. MUC20 allele frequencies and genotypes of IgAN patients were analyzed and compared with healthy population. In addition, the associations of MUC20 polymorphism with the clinical and pathological parameters at the time of renal biopsy were analyzed. The data followed up in different groups were compared. RESULTS: There was MUC20 VNTR polymorphism in healthy population with 2 - 6 repeats. The repeat fragment was 57bp. The most frequent alleles included 3(R(3)) and 4(R(4)) repeats; otherwise the least ones included 6(R(6)) repeats. The most frequent genotype was R(3)R(4), then R(3)R(3) and R(4)R(4); the least ones were R(2)R(2), R(3)R(6) and R(5)R(5). The frequencies of MUC20 alleles and genotypes in the IgAN patients were similar to healthy population. Initial ages, blood pressure, proteinuria, and renal function did not differ significantly among the three groups. There was no difference of the urinary osmotic pressure, urinary NAG (N-acetyl-B-D-glucosaminidase) and alpha1 microglobulin (alpha1-MG), and the semiquantitative scores of renal interstitial fibrosis and tubular atrophy in the three groups. IgAN patients with SL/LL genotype had higher odds ratio for progression of renal function (OR = 7.29, 95% CI: 1.68 - 31.60, P = 0.008) than the SS genotype. CONCLUSIONS: There were MUC20 VNTR polymorphisms in the healthy population. The polymorphism did not associate with the pathogenesis and the clinico-pathological parameters at the time of renal biopsy. The SL/LL genotype was likely to be a risk factor for rapid progression of renal function in the patients with IgAN.

[Uteroglobin G38A polymorphism is associated with the progression of IgA nephropathy in Chinese patients].

OBJECTIVE: Uteroglobin is a multifunctional protein. Both uteroglobin gene knockout and antisense transgenic mouse models developed the pathological and clinical features of IgA nephropathy. Uteroglobin G38A polymorphism has been reported to be associated with the progression of IgA nephropathy in some Caucasian and Asian populations, but there are no documents on Chinese population. The present report was to investigate the associations of uteroglobin G38A polymorphism with the development and progression of IgA nephropathy in Chinese patients. METHODS: Three hundred patients with biopsy proven IgA nephropathy were identified from Renal Disease database. Ninety-three patients had been followed-up for 2-6 years. 145 healthy donors served as normal controls. Genomic DNAs were extracted from peripheral blood leucocytes. The uteroglobin G38A polymorphism was determined by PCR-RFLP. Uteroglobin G38A genotype and allele frequency were compared between patients with IgA nephropathy and normal controls. In addition, associations of G38A polymorphism with blood pressure, hematuria, proteinuria, pathological lesions and prognosis of renal function were analyzed in patients with IgA nephropathy. RESULTS: Distribution of uteroglobin G38A polymorphism in patients with IgA nephropathy (38AA: 13.2%; 38AG: 57.6%; 38GG: 30.2%) and normal controls (38AA: 18.2%; 38AG: 60%; 38GG: 21.8%; P > 0.05) showed no difference. But patients with the 38AA genotype showed a higher odds ratio for progression of renal function (OR = 2.37, 95% CI = 1.12-5.01) as compared to patients with the 38AG/GG genotype. CONCLUSION: Uteroglobin G38A polymorphism had no association with the development of IgA nephropathy, but the homogeneous 38AA genotype maybe one of the genetic markers for disease progression in Chinese IgA nephropathy.

[Familial membranous nephropathy: an analysis of 3 kindreds and literature review].

OBJECTIVE: To report three kindreds of familial membranous nephropathy and describe its clinical and pathological characteristics. METHODS: 6 patients with renal biopsy proved familial membranous nephropathy from 3 kindreds were described. Their clinical and pathological data were compared with 33 patients who were also suffering from familial membranous nephropathy from 16 kindreds documented in PubMed and 30 sporadic patients who were collected in our hospital with membranous nephropathy. RESULTS: Compared with the patients documented in the literatures, the patients were older and the ratios of male and female patients in this series were equal. In both series, the pathological lesions were severe. Compared with sporadic patients with membranous nephropathy, the patients in familial form had severer pathological lesions. There were no differences among all patients in clinical manifestations, such as proteinuria, hypertension and renal function. The major clinical symptom in familial membranous nephropathy patients was nephritic syndrome. CONCLUSIONS: The present study first reported the kindreds of familial membranous nephropathy in China. The clinical manifestations of familial membranous nephropathy in our patients, as well as in other familial cases reported to date, are similar with those in the non-familial membranous nephropathy patients, but the pathological changes in the familial cases were severer than those in the non-familial. To distinguish the familial form from idiopathic membranous nephropathy, it is essential to understand the genetic factors underlying this disease.