Editor\u27s Notes, Chiba Medical Journal 90-1

Multiple sequence alignment of deduced amino acid sequences of 25 wheat annexin genes with rice annexin OsAnn2 (Os05g31760) obtained by ClustalW. (PDF 212 kb

Image_1_Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.tif

BackgroundThe large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.Case presentationWe report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.ConclusionsWe reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.</p

Table_2_Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.docx

BackgroundThe large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.Case presentationWe report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.ConclusionsWe reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.</p

Table_1_Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.docx

BackgroundThe large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.Case presentationWe report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.ConclusionsWe reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.</p

Table_3_Primary pure large cell neuroendocrine carcinoma of the urinary bladder: a case report and literature review.docx

BackgroundThe large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is a rare malignancy. With its high aggressiveness and poor prognosis, the disease is often accompanied by metastasis or recurrence. The lack of specific clinical manifestations and imaging features causes considerable challenges for clinical diagnosis and treatment.Case presentationWe report a case of LCNEC of the urinary bladder. The patient was a 79-year-old male admitted to our hospital with recurrent episodes of asymptomatic gross hematuria. Based on the computed tomography (CT) scan findings, our patient presented with a bladder mass displaying invasion into the serosal layer, suggestive of muscle involvement and indicative of malignancy. The patient received a radical cystectomy, and the postoperative pathology confirmed primary, pure LCNEC of the urinary bladder. We gave him 16 cycles of toripalimab immunotherapy. As of follow-up, the patient was alive, and periodic CT reexamination showed no evidence of recurrence.ConclusionsWe reviewed domestic and foreign literature and found no explicit treatment protocols exist for the disease. Surgical resection combined with chemotherapy were the most common treatments. Herein, we reported the first case of primary, pure LCNEC of the urinary bladder treated by radical cystectomy combined with pure immunotherapy, achieving sustained remission, which provides a new idea for the immunotherapy and integrative treatment of the disease.</p

Morphological and immunohistochemical analysis of mutant mice.

<p>(<b><i>A</i></b><b>–</b><b><i>D</i></b>) Representative immunofluorescence staining with prestin (green) and myosin 6 (red) in whole-mount preparations of basal cochlear turns (corresponding to the 60 kHz region of the +/+ cochlea) in the indicated mouse genotypes at P24. 4′, 6-diamidino-2-phenylindole (DAPI) counterstain is shown in blue. Scale bar: 20 µm. <i>Neo/Neo</i> and <i>Neo/-</i> mice show no OHC loss or abnormal distribution of prestin. (<b><i>E</i></b>) Length of OHCs of each genotype at a given location corresponding to 16 kHz region of the +/+ cochlea. Values are the mean ± SEM; **: <i>P</i><0.01, *: <i>P</i><0.05. (<b><i>F</i></b>) Length of OHCs of each genotype at different locations of the cochlea. The shorter OHCs could reduce the mass of the organ of Corti and result in a higher frequency response for a given location, assuming all other material properties remain the same. The x-axis displays a normalized distance from apex (0%) to base (100%). That is, the locations responding to 4, 6, 12, 16, and 22 kHz in wild-type cochleae correspond to 4, 12, 30, 40, and 51% in a normalized distance from the cochlear apex, respectively. Calculated intercepts for each genotype differed significantly by one-way ANOVA, followed by Student's t test with a Bonferroni correction.</p

<i>Prestin</i> knock-in mice.

<p>(<b><i>A</i></b>) Targeted Neo <i>prestin</i> knock-in allele. Solid rectangles represent exons 5 through 9. Diamond indicates the C1 mutation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045453#pone.0045453-Gao1" target="_blank">[9]</a>. A neo-selectable marker was inserted into intron 6 of the <i>prestin</i> gene in ES cells by homologous recombination. (<b><i>B</i></b>) Genomic Southern blot analysis of <i>Neo/Neo</i> mice. Genomic DNAs from <i>+/+</i> and <i>Neo/Neo</i> tails were digested with <i>Bam</i>HI and a specific probe indicated in (<b><i>A</i></b>) was used to detect a 12-kb band in the <i>+/+</i> allele and an 8-kb band in the targeted allele. (<b><i>C</i></b>) PCR-based genotyping of <i>+/+</i> and <i>Neo/Neo</i> mice using 3 primers is indicated in (<b><i>A</i></b>). Wild-type mice showed a 242-bp band; the <i>Neo/Neo</i> mice showed a 400-bp band.</p

Function parameters of OHCs from the 4 genotypes of mice.

<p>Note:</p>**<p>: p<0.01,</p>*<p>: p<0.05, compared to wild-type OHCs, as determined by the Kruskal-Wallis test followed by Student's t test with a Holm correction; NA: not applicable.</p

The relationship between prestin activity/feedback efficiency and amplification gain.

<p>The relationship between amplification gain and feedback efficiency proposed by Patuzzi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045453#pone.0045453-Patuzzi1" target="_blank">[7]</a> is plotted as a black curve. Y-axes represent the input/output (y/x) ratio (left) and the amplification gain [dB SPL = 20log(y/x), right], respectively. The amplification gain (dB SPL) for each genotype is the ABR threshold difference between prestin <i>−/−</i> mice and wild-type, <i>Neo/Neo</i>, or <i>Neo/-</i> mice. Mean values derived from our data are color-coded according to genotype. In this study, averaged ABR threshold changes at 16 kHz were used to derive the amplification gain, although similar results were obtained at frequencies of 4–12 and 22 kHz. We assumed that the prestin amount was linearly correlated with <i>Q</i>_max, charge density or electromotility, which is further linearly correlated with feedback efficiency. Therefore, the normalized prestin activity in <i>Neo/Neo</i> and <i>Neo/-</i> OHCs by wild-type control (100% prestin activity) is expressed as the feedback efficiency (β). Values are the mean ± SEM.</p

DPOAE (<i>A</i>) and ABR (<i>B</i>) thresholds of P21–24 mice of the indicated genotypes.

<p>Values are the mean ± SEM; **: <i>P</i><0.01, *: <i>P</i><0.05 by two-way ANOVA followed by Student's t test with a Bonferroni correction.</p