[Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells].

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

Effects of pelvic floor muscle exercise on faecal incontinence in rectal cancer patients after stoma closure.

The purpose of this study was to examine the effects of pelvic floor muscle exercise (PFME) on the faecal incontinence (FI) of rectal cancer patients following stoma closure. Participants were randomly distributed into an exercise group (n = 27) and non-exercise group (n = 26). An experimental design and longitudinal approach were implemented for data collection. Baseline data were collected at 1 day before discharge, and then PFME was taught before the patients were discharged from the hospital. We collected data and followed up with the patients at their pre-discharge visit and at 1, 2, 3, 6 and 9 months after discharge. The Cleveland Clinic Faecal Incontinence (CCI) score was used to measure patient outcome. PFME proved to effectively decrease the degree of FI in stoma closure recipients. The FI score of the exercise group significantly decreased from 8.37 to 2.27 after PFME compared with that of the non-exercise group (from 8.54 to 2.58). The generalised estimation equation tests showed that both group and time were significantly different. The tests also indicated that although PFME appeared to hasten the decline of incontinence, this effect was no longer detectable at 9 months; thus, it may be an effective intervention for FI when implemented up to half a year after discharge.

Melanotic oncocytic metaplasia of the nasopharynx.

We report a rare case of melanotic oncocytic metaplasia of the nasopharynx in a 63-year-old man, presenting as several black nodules up to several millimeters at the nasopharynx. It is a benign mimicker of malignant melanoma.

Clear cell adenocarcinoma of the renal pelvis: an extremely rare neoplasm of the upper urinary tract.

Clear cell adenocarcinoma (CCA) in the urinary tract is a rare neoplasm morphologically identical to the Müllerian counterpart. Clear cell adenocarcinoma is extremely rare in the upper urinary tract. We present a case with CCA of the renal pelvis. Microscopically, the tumor exhibited exophytic growth with predominantly tubulocystic structures, as well as solid and papillary patterns. The neoplastic cells were cuboidal with clear to pale eosinophilic cytoplasm and abundant intracellular and extracellular eosinophilic hyaline globules. By immunohistochemically, the tumor was labeled by cytokeratins and hepatocyte nuclear factor-1ß. The patient was still alive without evidence of recurrence in the follow-up period of nineteen months after diagnosis.

Dynamin 2 mediates PDGFRα-SHP-2-promoted glioblastoma growth and invasion.

Dynamin 2 (Dyn2), a large GTPase, is involved in receptor tyrosine kinase (RTK)-promoted cell migration. However, the molecular mechanisms by which Dyn2 regulates RTK-induced cell migration have not been established. Recently, we reported that tyrosine-protein phosphatase non-receptor type 11 (SHP-2) and phosphatidylinositol 3-kinase (PI3K) mediate platelet-derived growth factor receptor-α (PDGFRα)-promoted glioma tumor growth and invasion. Here, we show that Dyn2 is an effector downstream of the PDGFRα-PI3K/SHP-2 signaling in glioma cells. Depletion of endogenous Dyn2 by short hairpin RNAs (shRNAs) inhibited PDGFRα-stimulated phosphorylation of Akt, Erk1/2, Rac1 and Cdc42 activities, glioma cell migration and survival in vitro and tumor growth and invasion in the brains of mice. Dyn2 binds to SHP-2 and PI3K and colocalizes with PDGFRα at the invasive fronts in PDGF-A-stimulated glioma cells. Inhibition of SHP-2 by siRNA knockdown abrogated Dyn2 association with activated PDGFRα and PDGFRα activation of Rac1 and Cdc42, and glioma cell migration, thereby establishing a link between SHP-2 interaction with Dyn2 and the PDGFRα signaling. Furthermore, a dominant-negative SHP-2 C459S mutant inhibited PDGF-A-stimulated glioma cell migration, phosphorylation of Dyn2 and concomitantly blocked PDGFRα-induced Src activation. Inhibition of Src by Src inhibitors attenuated PDGF-A-stimulated phosphorylation of Akt and Dyn2 and glioma cell migration. Additionally, mutations of binding sites to PI3K, SHP-2 or Src of PDGFRα impaired PDGFRα-stimulated phosphorylation of Akt and Dyn2, and Dyn2 association with activated PDGFRα. Taken together, this study identifies Dyn2 as an effector that mediates PDGFRα-SHP-2-induced glioma tumor growth and invasion, suggesting that targeting the PDGFRα-SHP-2-Dyn2 pathway may be beneficial to patients with malignant glioblastomas.

A case of young-onset dementia.

Dementia is a major worldwide public health concern in view of the global ageing phenomenon. Dementia usually occurs in old age. However, if the symptoms occur in young patients, the diagnosis can be challenging. Posterior cortical atrophy is a variant of the Alzheimer's disease, which is described as a presenile disease affecting relatively late-middle-aged patients. A combination of clinical, neuropsychological, and neuroimaging techniques may facilitate making a diagnosis of this particular patient group, as demonstrated in this report. Although there is no effective disease-modifying agent for treating these patients to date, there may be considerable pressure to arrive at a quick and accurate diagnosis from the perspective of employment and insurance.

Medication prescribed to people with personality disorder: the influence of patient factors and treatment setting.

OBJECTIVE: To examine the extent of use and clinical rationale for the prescribing of psychotropic drugs for people with personality disorder (PD) who are in contact with mental health services. METHOD: Clinical records of 278 patients with a primary diagnosis of PD were examined. RESULTS: Just over 80% (N = 225) of patients were being prescribed psychotropic medication. One in five was prescribed three or more drugs. People with comorbid mental disorders were more likely to receive psychotropic medication. Half those prescribed antidepressants had no record of depression in their records. While drug treatments were mostly prescribed for depressive and psychotic symptoms, they were also used to try to manage behavioural problems such as self-harm or given in response to patient requests for treatment. People receiving specialist PD services (OR = 0.35, 95% CI = 0.13-0.95) or other specialist services (OR = 0.24, 95% CI = 0.10-0.60) were less likely to be prescribed drug treatments. CONCLUSION: Drug treatments are widely used for people with PD despite the relatively weak evidence base. Both the type of personality problem and the context in which treatment is delivered appear to have an impact on whether drug treatments are prescribed.

The impact of hemorrhoidectomy on sexual function in women: a preliminary study.

The purpose of this study was to explore the prevalence of sexual problems in post-hemorrhoidectomy females. The study consisted of a surgical group and a control group of women between the ages of 22 and 74 years, 39 with and 39 without hemorrhoidectomy. Female sexual function was evaluated using the Female Sexual Function Index (FSFI). The level of sexual function was calculated for each domain and compared across domains and demographic variables for each group. The prevalence of sexual dysfunction among the post-hemorrhoidectomy participants was 48.7% (19/39) and among the healthy women 7.7% (3/39). The average FSFI score was significantly lower in the surgical group (46.38+/-28.13) than in the control group (65.69+/-18.48) (P=0.001). All the FSFI domain scores, with the exception of the desire domain, were significantly lower for the surgical group relative to the healthy group (P<0.05). Logistic regression analysis revealed that group (P=0.001) and age (P=0.013) were predictors of problems in female sexual functioning. This preliminary study shows that women who have had a hemorrhoidectomy are at higher risk of sexual function problems. The sexual function of women with hemorrhoidectomy should be evaluated to provide them with a better quality of life.

Supported-employment program processes and outcomes: experiences of people with schizophrenia.

OBJECTIVE: This qualitative study explored participants' experiences of a supported-employment program. Understanding participants' opinions of a supported-employment program may provide insights into what processes and outcomes are meaningful and important for participants and may enable an evaluation of such processes and outcomes for their congruence with occupational therapy practice. METHOD: Supported-employment program participants with schizophrenia (N= 7) were recruited from an agency and interviewed individually with open-ended questions. Data were analyzed using a grounded-theory approach. RESULTS: We developed a tentative grounded theory with three themes of supported-employment program outcomes: (a) removing barriers to job seeking, (b) improving psychological well-being, and (c) participating in work. CONCLUSION: Supported-employment program participants can achieve meaningful personal outcomes even though they do not obtain competitive employment. These programs removed barriers to job seeking, but personal readiness and efforts in job seeking contributed most to obtaining employment.

Retroperitoneoscopic dismembered pyeloplasty for pelvi-ureteric junction obstruction in infants and children.

OBJECTIVE: To report our initial experience of endoscopic dismembered pyeloplasty through a retroperitoneal approach in infants and children with pelvi-ureteric junction (PUJ) obstruction. PATIENTS AND METHODS: Thirteen infants and children with PUJ obstruction underwent retroperitoneoscopic dismembered pyeloplasty (mean age at operation 2.7 years, range 0.25-10). Nine patients presented with complications secondary to PUJ obstruction, including urinary tract infection, pyonephrosis and increasing hydronephrosis with impairment in renal function. The other four patients had recurrent loin pain secondary to intermittent PUJ obstruction. The patient was placed in semi-prone (for left-sided) or a semilateral position (for right-sided PUJ obstruction). The retroperitoneal space was entered via a 1-cm incision over the mid-axillary line and further developed using a glove balloon. Video-retroperitoneoscopy was undertaken using a 5-mm laparoscope. Dismembered pyeloplasty was carried out with the pelvi-ureteric anastomosis fashioned using fine polydioxanone sutures over a double-pigtail ureteric stent. RESULTS: The retroperitoneoscopic dismembered pyeloplasty was successful in 12 patients, while one with previous percutaneous nephrostomy drainage for pyonephrosis required open conversion because of difficulties in developing the retroperitoneal space. The mean (range) operative duration was 143 (103-235) min. All patients had a rapid and uneventful recovery. The drainage was satisfactory in all 12 patients on a follow-up scan. CONCLUSIONS: Retroperitoneoscopic dismembered pyeloplasty is effective and safe in infants and young children giving a good early outcome, although the long-term results await further studies.

Laparoscopy as the investigation and treatment of choice for urinary incontinence caused by small 'invisible' dysplastic kidneys with infrasphincteric ureteric ectopia.

OBJECTIVE: To report our experience of using laparoscopy for the accurate location and simultaneous removal of small dysplastic kidneys with ectopic ureteric insertion causing urinary incontinence and that were not detected by conventional imaging modalities. PATIENTS AND METHODS: Seven girls (mean age 7.9 years, range 3.5-13) presented with urinary leakage occurring between normal voids. Imaging studies including ultrasonography, renal scintigraphy, intravenous urography, computed tomography and/or magnetic resonance imaging in six of the seven patients revealed a single normal functioning kidney, but failed to detect the contralateral nonfunctioning dysplastic kidney. All patients were examined under anaesthesia, followed by transperitoneal laparoscopy for the simultaneous localization and removal of the dysplastic kidneys under the same setting. RESULTS: Laparoscopy in all seven patients revealed a small dysplastic kidney that could always be easily located by first finding the draining ureter over the iliac vessels and then following it upwards. Four dysplastic kidneys were found in the renal fossa (two left, two right). One kidney was found at the left iliac fossa just above the pelvic brim, one at the left lumbar region, and the other at the right iliac fossa. Laparoscopic nephroureterectomy was successful in all seven girls and the patients were discharged 48 h after surgery. The follow-up (mean 2.7 years, range 3 months-5.4 years) showed excellent cosmetic results and all the patients have remained completely dry. CONCLUSIONS: In patients with a classical picture of urinary incontinence caused by infrasphincteric ureteric ectopia associated with a small nonfunctioning kidney, video-laparoscopy, with its magnifying effect, can reliably confirm the diagnosis, locate the dysplastic kidney and allow its removal in the same setting. We propose that laparoscopy should be considered the investigation and treatment of choice in such patients, and should be undertaken without delay even if the dysplastic kidney or the ectopic ureteric orifice cannot be identified with all other conventional means.

Acute scrotal swelling: a sign of neonatal adrenal haemorrhage.

Two neonates presented with acute scrotal swelling suggestive of testicular torsion. Surgical exploration in one patient revealed an infected haematoma. Subsequent investigations including ultrasonography and urinary catecholamine determination disclosed adrenal haemorrhage as the cause of the scrotal haematoma. A second patient in whom a purplish discolouration of the right hemiscrotum was noted was also investigated with ultrasonography, which revealed a normal right testis and a right adrenal haematoma. Both cases of adrenal haemorrhage resolved spontaneously on conservative treatment. Adrenal haemorrhage should be considered as a possible cause of acute scrotal swelling in neonates. Ultrasonography assessment should be performed in such cases to examine the intra-abdominal organs especially the adrenal glands.

Childhood abdominal tuberculosis. The role of echo-guided fine-needle aspiration in its management.

Two children presented with abdominal tuberculosis. Because of the nonspecific clinical features, the diagnosis required a high index of clinical suspicion. Fine-needle aspiration (FNA) under ultrasonographic guidance allowed an early definitive diagnosis and bacteriological confirmation to guide chemotherapy. Both patients responded well to antituberculous chemotherapy.

Going deep into chemical burns.

This is a five year retrospective study of chemical burn injury in our burn center between 1 January 1987 and 31 December 1991. Of the 1,226 total burn cases, 131 patients had chemical burns. We noted a constant prevailing incidence of 10.7% per year. Males (72%) are more common than females (28%). Most of those injured are in the working age group (65%). Majority of cases had deep full thickness burn involving less than 10% of their total body surface area. Sulfuric acid is the most common chemical agent encountered. We had three mortality cases with deep third degree burns covering 60% of their total body surface area. Some clinical cases are demonstrated. Lastly, proposed solutions for the prevention of chemical burns are cited.