Microscopic Replantation of Penile Glans Amputation Due to Circumcision

Circumcision using a disposable stapler is becoming quite popular in China. However, improper surgical procedures also bring the risk of penile glans ...

Army Medical University

To investigate the surgical outcomes of vesiculoscopy on refractory hematospermia and ejaculatory duct obstruction (EDO), the clinical data (including pelvic magnetic resonance imaging (MRI) examinations and the long-term effects of endoscopic treatment) from 305 patients were analyzed. Four main etiologic groups were found on MRI. We found that 62.0% (189/305) of patients showed abnormal signal intensity in MRI investigations in the seminal vesicle (SV) area. Cystic lesions were observed in 36.7% (112/305) of the patients. The third sign was dilatation or enlargement of unilateral or bilateral SV, which were observed in 32.1% (98/305) of the patients. The fourth sign was stone formation in SV or in an adjacent cyst, which was present in 8.5% (26/305) of the patients. The transurethral endoscopy or seminal vesiculoscopy and the related procedures, including fenestration in prostatic utricle (PU), irrigation, lithotripsy, stone removal, biopsy, electroexcision, fulguration, or transurethral resection/incision of the ejaculatory duct (TURED/TUIED), chosen according to the different situations of individual patients were successfully performed in 296 patients. Fenestrations in PU+ seminal vesiculoscopy were performed in 66.6% (197/296) of cases. Seminal vesiculoscopy via the pathological opening in PU was performed in 10.8% (32/296) of cases. TURED/TUIED + seminal vesiculoscopy was performed in 12.8% (38/296) of cases, and seminal vesiculoscopy by the natural orifices of the ejaculatory duct (ED) was performed in 2.4% (7/296) of cases. Electroexcision and fulguration to the abnormal blood vessels or cavernous hemangioma at posterior urethra were performed in 7.4% (22/296) of cases. Two hundred and seventy-one patients were followed up for 6-72 months. The hematospermia of all the patients disappeared within 2-6 weeks, and 93.0% of the patients showed no further hematospermia during follow-up. No obvious postoperative complications were observed. The transurethral seminal vesiculoscopy technique and related procedures are safe and effective approaches for refractory hematospermia and EDO.

Etiology of 305 cases of refractory hematospermia and therapeutic options by emerging endoscopic technology.

The aim of this study was to summarize in a literature review our treatment experience involving microscopic replantation in a rare case of a completely amputated penis and testes.

Microscopic replantation of completely amputated penis and testes: a case report and literature review.

Patient‑derived orthotopic glioma xenograft models are important platforms used for pre‑clinical research of glioma. In the present study, the diagnostic ability of magnetic resonance imaging (MRI) was examined with regard to the identification of biomarkers obtained from patient‑derived glioma xenografts and human tumors. Conventional MRI, diffusion weighted imaging and dynamic contrast‑enhanced (DCE)‑MRI were used to analyze seven pairs of high grade gliomas with their corresponding xenografts obtained from non‑obese diabetic‑severe‑combined immunodeficiency nude mice. Tumor samples were collected for transcriptome sequencing and histopathological staining, and differentially expressed genes were screened between the original tumors and the corresponding xenografts. Gene Ontology (GO) analysis was performed to predict the functions of these genes. In 6 cases of xenografts with diffuse growth, the degree of enhancement was significantly lower compared with the original tumors. Histopathological staining indicated that the microvascular area and microvascular diameter of the xenografts were significantly lower compared with the original tumors (P=0.009 and P=0.007, respectively). In one case, there was evidence of nodular tumor growth in the mouse. Both MRI and histopathological staining showed a clear demarcation between the transplanted tumors and the normal brain tissues. The relative apparent diffusion coefficient values of the 7 cases examined were significantly higher compared with the corresponding original tumors (P=0.001) and transfer coefficient values derived from DCE‑MRI of the tumor area was significantly lower compared with the original tumors (P=0.016). GO analysis indicated that the expression levels of extracellular matrix‑associated genes, angiogenesis‑associated genes and immune function‑associated genes in the original tumors were higher compared with the corresponding xenografts. In conclusion, the data demonstrated that the MRI features of patient‑derived xenograft glioma models in mice were different compared with those of the original patient tumors. Differential gene expression may underlie the differences noted in the MRI features between original tumors and corresponding xenografts. The results of the present study highlight the precautions that should be taken when extrapolating data from patient‑derived xenograft studies, and their applicability to humans.

Patient‑derived orthotopic xenograft glioma models fail to replicate the magnetic resonance imaging features of the original patient tumor.

Neovascularization is required in high-grade glioma (HGG). The objective of this study was to explore neovascularization-related genes and their corresponding MRI biomarkers during the early-growth stage of HGG. Tumor tissues from 30 HGG patients underwent perfusion MRI scanning prior to surgery were used to establish orthotopic xenograft models, pathologically analyze the tumor vasculature and perform transcriptome sequencing. The cases were divided into two groups based on whether the xenograft was successfully established. Microvascular density and BMPER, CXCL10, and HOXA9 expression of surgical specimens in the xenograft-forming group was significantly elevated and the microvascular diameter was significantly reduced,  inhibition of BMPER, CXCL10, or HOXA9 in the glioma stem cell significantly suppressed its tube formation abilities. The  experiment showed that BMPER was highly expressed in the early tumor growth phase (20 days), CXCL10 and HOXA9 expression was elevated with tumor progress, and spatially associated with tumor vasculature. Perfusion weighted MRI (PWI-MRI) derived parameters, rCBV, rCBF, K, and V, were also increased in the xenograft-forming group. In conclusion BMPER, CXCL10, and HOXA9 promote early tumor growth and progression by stimulating neovascularization of primary HGG. The rCBV, rCBF, K, and V can be used as imaging biomarkers to predict the expression statuses of these genes.

Effects of BMPER, CXCL10, and HOXA9 on Neovascularization During Early-Growth Stage of Primary High-Grade Glioma and Their Corresponding MRI Biomarkers.

 Tumor vascular normalization (TVN) is emerging to enhance the efficacy of anticancer treatment in many cancers including glioblastoma (GBM). However, a common and severe challenge being currently faced is the transient TVN effect, hampering the sustained administration of anticancer therapy during TVN window. Additionally, the lack of non-contrast agent-based imaging biomarkers to monitor TVN process postpones the clinical translation of TVN strategy. In this study, we investigated whether dual inhibition of VEGF and the glycolytic activator PFKFB3 could reinforce the TVN effect in GBM. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM)-MRI were performed to monitor TVN process and to identify whether IVIM-MRI is a candidate or complementary imaging biomarker for monitoring TVN window without exogenous contrast agent administration.  Patient-derived orthotopic GBM xenografts in mice were established and treated with bevacizumab (BEV), 3PO (PFKFB3 inhibitor), BEV+3PO dual therapy, or saline. The vascular morphology, tumor hypoxia, and lactate level were evaluated before and at different time points after treatments. Doxorubicin was used to evaluate chemotherapeutic efficacy and drug delivery. Microarray of angiogenesis cytokines and western blotting were conducted to characterize post-treatment molecular profiling. TVN process was monitored by DCE- and IVIM-MRI. Correlation analysis of pathological indicators and MRI parameters was further analyzed.  Dual therapy extended survival and delayed tumor growth over each therapy alone, concomitant with a decrease of cell proliferation and an increase of cell apoptosis. The dual therapy reinforces TVN effect, thereby alleviating tumor hypoxia, reducing lactate production, and improving the efficacy and delivery of doxorubicin. Mechanistically, several angiogenic cytokines and pathways were downregulated after dual therapy. Notably, dual therapy inhibited Tie1 expression, the key regulator of TVN, in both endothelial cells and tumor cells. DCE- and IVIM-MRI data showed that dual therapy induced a more homogenous and prominent TVN effect characterized by improved vascular function in tumor core and tumor rim. Correlation analysis revealed that IVIM-MRI parameter   had better correlations with TVN pathological indicators compared with the DCE-MRI parameter  .  Our results propose a rationale to overcome the current limitation of BEV monotherapy by integrating the synergistic effects of VEGF and PFKFB3 blockade to enhance chemotherapy efficacy through a sustained TVN effect. Moreover, we unveil IVIM-MRI parameter   has much potential as a complementary imaging biomarker to monitor TVN window more precisely without exogenous contrast agent injection.

Dual inhibition of PFKFB3 and VEGF normalizes tumor vasculature, reduces lactate production, and improves chemotherapy in glioblastoma: insights from protein expression profiling and MRI.

Transmembrane and ubiquitin-like domain-containing 1 (Tmub1) inhibits hepatocyte proliferation during liver regeneration, but its role in hepatocellular carcinoma (HCC) has yet to be revealed. In this study, we show that the levels of Tmub1 were significantly lower in HCC tissues and cells than they were in adjacent tissues and normal hepatic cells, and the low levels of Tmub1 indicated a poor prognosis in HCC patients. Xenograft growth assay revealed that Tmub1 represses HCC growth . In addition, Tmub1 formed a protein complex with apoptosis-associated protein tumor protein 63 (p63), especially with the ΔN isoforms (ΔNp63α, β, and γ). Further loss- and gain-of-function analyses indicated that Tmub1 promotes apoptosis of Hep3B and MHCC-LM3 cells. Tmub1 decreased the protein expression of ΔNp63, and the pro-apoptotic effect of Tmub1 can be reversed by ΔNp63 isoforms (α, β, and γ). Additionally, we report that Tmub1 promotes the ubiquitination and degradation of ΔNp63 proteins. Finally, we confirmed in HCC tissues that Tmub1 is negatively correlated with ΔNp63 and positively correlated with the level of apoptosis. Taken together, Tmub1 suppresses HCC by enhancing the ubiquitination and degradation of ΔNp63 isoforms to induce HCC cell apoptosis. These findings provide a potential strategy for the management of HCC.

Tmub1 Suppresses Hepatocellular Carcinoma by Promoting the Ubiquitination of ΔNp63 Isoforms.

Spinocerebellar ataxia type 3 (SCA3) is an inherited motor disorder that is characterized by low body mass index (BMI). Considering the role of the hypothalamus in regulating appetitive behaviors and metabolism, low BMI may result from hypothalamic degeneration.

Bo Zhou

Department of Urology,
Daping Hospital,
Department of Urology, Daping Hospital

Army Medical University

Microscopic Replantation of Penile Glans Amputation Due to Circumcision

Bo Zhou

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Army Medical University

Microscopic Replantation of Penile Glans Amputation Due to Circumcision

Department of Urology,
Daping Hospital,
Department of Urology, Daping Hospital