Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study.

BACKGROUND: Some head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC. METHODS: A case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc. RESULTS: 114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50-1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50-1.50; P = 0.76) was observed with no PORT. CONCLUSIONS: PORT isn't necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

MicroRNA-150 suppresses epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer through the TRPM4-mediated ß-catenin signaling pathway.

Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths among males. The aim of the current study was to investigate the ability of microRNA-150 (miR-150) targeting transient receptor potential melastatin 4 (TRPM4) to mediate epithelial-mesenchymal transition (EMT), invasion, and metastasis through the ß-catenin signaling pathway in PCa. Microarray analysis was performed to identify PCa-related differentially expressed genes, after which both the mirDIP and TargetScan databases were employed in the prediction of the miRNAs regulating TRPM4. Immunohistochemistry and RT-qPCR were conducted to determine the expression pattern of miR-150 and TRPM4 in PCa. The relationship between miR-150 and TRPM4 expression was identified. By perturbing miR-150 and TRPM4 expression in PCa cells, cell proliferation, migration, invasion, cycle, and apoptosis as well as EMT markers were determined accordingly. Finally, tumor growth and metastasis were evaluated among nude mice. Higher TRPM4 expression and lower miR-150 expression and activation of the ß-catenin signaling pathway as well as EMT stimulation were detected in the PCa tissues. Our results confirmed TRPM4 as a target of miR-150. Upregulation of miR-150 resulted in inactivation of the ß-catenin signaling pathway. Furthermore, the upregulation of miR-150 or knockdown of TRPM4 was observed to suppress EMT, proliferation, migration, and invasion in vitro in addition to restrained tumor growth and metastasis in vivo. The evidence provided by our study highlights the involvement of miR-150 in the translational suppression of TRPM4 and the blockade of the ß-catenin signaling pathway, resulting in the inhibition of PCa progression.

Kappa-opioid receptor agonist U50448H protects against renal ischemia-reperfusion injury in rats via activating the PI3K/Akt signaling pathway.

Renal ischemia-reperfusion injury (IRI) is regarded as a leading cause of acute kidney failure and renal dysfunction. Previous studies show that kappa opioid receptor (KOR) agonists can attenuate IRI in cardiomycytes and neuronal cells. In this study we explored the effects of a KOR agonist on renal IRI and the underlying mechanisms in vivo and in vitro. An IRI model was established in SD rats, which were intravenously pretreated with a KOR agonist U50448H (1 mg/kg), a KOR antagonist Nor-BNI (2 mg/kg) followed by U50448H (1 mg/kg), or the PI3K inhibitor wortmannin (1.4 mg/kg) followed by U50448H (1 mg/kg). U50448H pretreatment significantly decreased the serum levels of creatinine (Cr) and BUN, the renal tubular injury scores and the apoptotic index (AI) in IRI model rats. Furthermore, U50448H significantly increased SOD activity and NO levels, and reduced the MDA levels in the kidney tissues of IRI model rats. Moreover, U50448H significantly increased the phosphorylation of Akt, eNOS and PI3K in the kidney tissues of IRI model rats. All the beneficial effects of U50448H were blocked by Nor-BNI or wortmannin pre-administered. Similar results were observed in vitro in renal tubular epithelial NRK-52E cells subjected to a hypoxia-reoxygenation (HR) procedure. Our results demonstrate that the KOR agonist U50448H protects against renal IRI via activating the PI3K/Akt signaling pathway.

[Exploiture and application of an internet-based Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine].

Recently, integrative pharmacology(IP) has become a pivotal paradigm for the modernization of traditional Chinese medicines(TCM) and combinatorial drugs discovery, which is an interdisciplinary science for establishing the in vitro and in vivo correlation between absorption, distribution, metabolism, and excretion/pharmacokinetic(ADME/PK) profiles of TCM and the molecular networks of disease by the integration of the knowledge of multi-disciplinary and multi-stages. In the present study, an internet-based Computation Platform for IP of TCM(TCM-IP, www.tcmip.cn) is established to promote the development of the emerging discipline. Among them, a big data of TCM is an important resource for TCM-IP including Chinese Medicine Formula Database, Chinese Medical Herbs Database, Chemical Database of Chinese Medicine, Target Database for Disease and Symptoms, et al. Meanwhile, some data mining and bioinformatics approaches are critical technology for TCM-IP including the identification of the TCM constituents, ADME prediction, target prediction for the TCM constituents, network construction and analysis, et al. Furthermore, network beautification and individuation design are employed to meet the consumer's requirement. We firmly believe that TCM-IP is a very useful tool for the identification of active constituents of TCM and their involving potential molecular mechanism for therapeutics, which would wildly applied in quality evaluation, clinical repositioning, scientific discovery based on original thinking, prescription compatibility and new drug of TCM, et al.

Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal ß-amyloid deposition in the human brain.

BACKGROUND: Cerebral amyloid angiopathy (CAA) refers to the deposition of ß-amyloid (Aß) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aß deposition in leptomeninge. The cellular origin of angiopathic Aß and the pathogenic course of CAA remain incompletely understood. METHODS: The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in ß-secretase-1 (BACE1), the obligatory Aß producing enzyme, relative to Aß and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. RESULTS: Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aß deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. CONCLUSION: These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aß deposition, while BACE1 elevation in meningeal cells might contribute Aß to leptomeningeal amyloidosis.

Gibberellic acid targeting ZBTB16 reduces NF-κB dependent inflammatory stress in sepsis-induced neuroinflammation.

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.

Stellate Ganglion Block Improves Postoperative Sleep Quality and Analgesia in Patients with Breast Cancer: A Randomized Controlled Trial.

INTRODUCTION: Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. METHODS: This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary's Hospital Sleep Questionnaire and actigraphy 2 days postoperatively. The secondary outcome was postoperative pain, measured by the visual analog scale. RESULTS: A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary's Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1 day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P = 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P = 0.02, odds ratio 0.229, 95% confidence interval 0.064-0.821). There were no adverse events related to SGB. CONCLUSION: Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021).

Mouse model of plasma cell mastitis.

BACKGROUND: Plasma cell mastitis is distinct from the common form of mastitis and clinically resembles breast carcinoma. The lesion occurs in non-lactating young women, and the incidence rate is rising. Surgical resection is the main treatment, but cannot prevent recurrence of the disease. Disfigurement or removal of breast after the operations can cause marked physical and psychological distress. The etiology of plasma cell mastitis is unclear up till now. It is therefore necessary to investigate further the underlying immunological changes of the disease. METHODS: The lesions of plasma cell mastitis removed from patients through aseptic operation were mixed with normal saline into homogenate tube machine (homogenate tubes were disinfected and sterilized prior to treatment). The mixture was homogenized at medium speed and grinded in ultrasonic cell disruptor. The homogenate obtained was made into oil emulsion with Freund's adjuvant. Thirty female BALB/c mice (6 weeks after sexual maturity) were divided into five groups A-E: group A was blank control; group B was normal saline control; group C was inoculated with 0.02 ml water-in-oil emulsion; group D was inoculated with 0.04 ml water-in-oil emulsion; group E was complete Freund's adjuvant control. RESULTS: Pathology results showed that mouse mammary gland acinar cells remained integral without any abnormal changes observed in control groups A and B. Experimental groups C and D showed dilation of mouse mammary ductal tissue with a large number of epithelial cells and debris in the lumen, and fibrosis around ducts accompanied by large duct cells, neutrophils, lymphocytes, and especially plasma cell infiltration. Pathological changes were observed in 3 (50%) mice and 5 (83.3%) mice in group C and D respectively. In group E, neutrophil infiltration in mammary gland was observed in 5 mice, but neither infiltration of plasma cells nor other abnormal pathological changes were observed. CONCLUSIONS: The lesions of patient with plasma cell mastitis could make the female BALB/c mice experience the similar clinical and pathological manifestation. High-dose group can successfully establish a mouse model of plasma cell mastitis.

Minimally invasive video-assisted thyroidectomy for the early-stage differential thyroid carcinoma.

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT), the modified Miccoli's thyroid surgery, is the most widespread minimally invasive technique and has been widely used for treatment of thyroid disease. This study aimed to verify the potential benefits of the modified Miccoli's thyroid surgery, determine the feasibility of the MIVAT for early-stage differential thyroid carcinoma and evaluate the likelihood of the surgical method as a standard operation for early malignant thyroid carcinoma. METHODS: A total of 135 patients were retrospectively compared which included two groups of patients: the first group underwent the conventional thyroidectomy; the other group underwent MIVAT. Patients with thyroid nodule smaller than 20 mm and without previous neck surgery were included while those with wide-ranging and distant metastases of cervical tissues, or any suspected thyroid nodal metastases were excluded for analysis. MIVAT and the central compartment (level VI) lymph nodes dissection (LND) were considered as a new treatment method for this retrospective study. In addition to the comparison of surgical outcomes between the new treatment and the conventional thyroid surgery, other surgical parameters including operative time, operative volume of hemorrhage, incisional length, postoperative volume of drainage, length of hospitalization, accidence of hoarse voice, accidence of bucking, accidence of hypocalcemia and peak angle of cervical axial rotation were also compared. RESULTS: Out of 135 patients, 111 patients underwent conventional thyroid surgery and 24 patients underwent MIVAT plus level VI LND for treatment of early-stage differential malignant carcinoma. Patients who received the new surgical treatment had significantly shorter incisional length (3.1 cm vs. 6.9 cm, p < 0.0001), shorter operative time (109 min vs. 139 min, p = 0.014) and fewer operative hemorrhage (29.5 ml vs. 69.7 ml, p < 0.0001) when compared to the conventional treatment. Postoperative peak angle of cervical axial rotation of patients treated with MIVAT was less than those treated with conventional surgery (L: 31.5° vs. 39.0°, p < 0.0001; R: 31.5° vs. 38.0°, p < 0.0001). Incisional wound infection, postoperative hoarse voice, bucking and hypocalcemia were not observed in all patients. Postoperative analgetica was not required as well. CONCLUSIONS: Compared with conventional thyroid surgery for early-stage differential thyroid carcinoma, the new surgical treatment could be considered as an alternative surgical method for treatment of early-stage thyroid carcinoma since it was feasible, safe and clinically effective with better surgical and cosmetic outcomes.

Association of testicular p63 expression and spermatogenesis in androgen receptor knockout (ARKO) mice.

OBJECTIVE: To study changes of testicular p63 expression and its effect on spermatogenic function in seminiferous tubules in androgen receptor knockout (ARKO) mice. METHODS: A total of 28 ARKO mice (ARKO group) screened by Cre-lox and 28 male Wistar mice without ARKO (controlled group) were enrolled in our study. Route pathology was performed and p63 examination was detected by immunohistochemistry in testes. Linear correlations were used to explore potential associations between p63 protein expression and spermatogenic function (TMS score). RESULTS: In ARKO group, inner diameter of seminiferous tubules was decreased (62 +/- 1.3 microm vs. 91 +/- 1.2 microm), thickness of the basal membrane of the tubules (4 +/- 0.3 microm vs. 2.7 +/- 0.5 microm), cellular population within tubules was reduced (2 +/- 0.4 vs. 4 +/- 0.1 layers), degree of spermatogenesis within the tubules turned to disturbance (3 +/- 1.0 vs. 5 +/- 0.1), Testicular Makler score was lower than controlled group (7 +/- 0.2 vs.15 +/- 0.3), they had significant differences (p <0.01). P63 expressed significantly lower in ARKO group than that in Wistar group, and was limited at stages from spermatocyte to round spermatid. (Percentage of positive cells ? 68.1 +/- 3.7 vs. 81.7 +/- 5.1, p<0.001). The HSCORE yielded similar results (HSCORE 3.7 +/- 0.3 vs. 2.0 +/- 0.2, p<0.001). p63 protein expression was significantly positively correlated with spermatogenic function (r=0.87, p<0.01). CONCLUSIONS: p63 developed important effect on spermatogenesis and the regulatory effect of p63 on spermatogenesis mainly occurred in the early stage of spermiogenesis in testis.

The comparison of two experimental rat varicocele models and their effect on sperm quality.

OBJECTIVE: To develop a modified rat varicocele model. METHODS: 300 male Sprague-Dawley rats were selected. In 82 rats (classic group, CG), this was achieved by dissecting the left renal vein and ligating it using a 0.8-mm metal clip and 3-0 silk suture proximal to the inferior vena cava, followed by removal of the bar. In 118 rats (modified group, MG), in addition to the partial ligation of the left renal vein, the communicating branch was fully ligated. In 100 rats (sham operation group, SG), the left renal vein and communicating branches were dissected, but not ligated. The seminal fluid was aspirated and the diameters of the left spermatic veins were analyzed. Three months later, the examination was performed again. RESULTS: The diameters were 0.16 ± 0.1 mm and 1.88 ± 0.1 mm before and after operation, respectively, in the CG (p < 0.01), and 0.15 ± 0.05 mm and 2.0 ± 0.1 mm in the MG (p < 0.01). Postsurgical diameters in the CG and MG were 1.88 ± 0.1 mm and 2.0 ± 0.1 mm (p > 0.5), and 0.16 ± 0.1 mm and 0.16 ± 0.11 mm in the SG (p > 0.5). Semen parameters in the CG had significant differences before and after the operation (p < 0.01), were significantly lower in the MG (p < 0.01), and had no significant differences in the SG (p > 0.5). CONCLUSION: Simple partial ligation of the renal vein combined with ligation of the communicating branch leads to acceptable models for varicocele.

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer.

BACKGROUND: The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. METHODS: A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. RESULTS: Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). CONCLUSIONS: Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

Effect of mtDNA mutation on tumor malignant degree in patients with prostate cancer.

OBJECTIVES: To understand mtDNA mutation frequency in patients with prostate cancer (Pca) and its effect on malignant degree of PCa. METHODS: A total of 130 patients (mean age, 70.1 +/- 2.4; range, 58-97 years) undergoing either prostate biopsy or radical prostatectomy between October 2006 and March 2008 were included. Additionally, 61 patients with benign prostatic hyperplasia (mean age, 69.9 +/- 1.1; range, 60-92 years) were included as a control group. The normal cells were isolated from each prostate cancer specimen by microdissection. Mitochondrial DNA (mtDNA4977) deletion mutations were identified by polymerase chain reaction. Gleason scores were determined by histopathology. RESULTS: Among the 130 Pca samples vs. 61 BPH samples, mtDNA4977 deletion mutation was detected in 98 cases (98/130, 75.4%) vs. in 9 cases (9/61, 14.7%) (P < 0.01, P = 0.001). There was a significantly higher prevalence of the mtDNA4977 deletion mutation in patients with prostate cancer compared to patients with BPH (P < 0.01). The incidence of the mtDNA4977 deletion in normal cells isolated from cancer specimen was 10.76% (14/130), which was significantly lower than that in prostate cancer group(P < 0.01). However, there was no significant difference versus BPH group (P > 0.5). Gleason scores were significantly higher in the group of patients with cancer with the mutation (7.6 +/- 2.4), compared to those without the mutation (6.2 +/- 1.1, P < 0.01). Logistic regression analysis demonstrated that Gleason scores (OR = 1.642, 95% CI: 1.232-2.183) and age (OR = 1.061, 95% CI: 1.041-1.082) are both independent predictors of the mtDNA4977 deletion mutations. CONCLUSIONS: mtDNA4977 deletion mutation frequency may be useful as a biomarker in malignant degree appraisal in patients with Pca.

Diagnostic puzzle of inflammatory pseudotumor of the urinary bladder: a case report with brief literature review.

Inflammatory pseudotumor of the urinary bladder is a rare reactive proliferation with a clinical presentation similar to malignant neoplasms. We present the case of a 35-year-old woman who presented with left lower quadrant pain and gross hematuria. A diagnosis of cystitis glandularis was initially considered; however, the symptoms did not resolve following transurethral resection. Subsequently, a partial cystectomy was performed after malignancy was excluded based on intraoperative frozen sections. Further histopathological evaluation confirmed the diagnosis of inflammatory pseudotumor.

[Mitochondrial function score combined with Gleason score for predicting the progression of prostate cancer].

OBJECTIVE: To evaluate the mitochondrial function score in combination with Gleason score in predicting the progression of prostate cancer. METHODS: This study included twenty 58-79 (70.1 +/- 1.2) years old patients with prostate cancer treated by radical prostatectomy. The epithelioglandular mitochondrial function scores of the patients were obtained under the transmission electron microscope and assessed according to Flameng grading. Meanwhile, their Gleason scores were analyzed and, based on the scores, the patients were divided into Groups I (Gleason score: 2 -4) and II (Gleason score: 5 -7). RESULTS: The mitochondrial function score of Group I was significantly different from that of Group II (4.0 +/- 0.8 versus 2.3 +/- 0.6, P < 0.05), with a negative correlation with the Gleason score (r = -0.793, P < 0.05). One year follow-up showed a significantly lower mortality in Group I (0/8) than in Group II (6/12) (P < 0.05). CONCLUSION: Mitochondrial dysfunction exists in prostate cancer patients, particularly in those with higher malignancy. The mitochondrial function score combined with Gleason score plays a valuable role in predicting the progression of prostate cancer.

[Improved experimental varicocele increases follicle-stimulating hormone and reduces inhibin B in rats].

OBJECTIVE: To evaluate the effects of improved experimental left varicocele (ELV) on follicle-stimulating hormone (FSH) and inhibin B (InhB). METHODS: ELV models were established by the improved method in 30 SD rats, and another 30 were included in a sham operation group as controls. Three months after the operation, the concentrations of the FSH and InhB were assayed by ELISA. RESULTS: The concentration of FSH in the serum was significantly higher in the experimental group ([37.56 +/- 9.72] ng/ml) than in the control ([26.69 +/- 5.33] ng/ml) (P < 0.05), while that of InhB significantly lower in the former ([349.93 +/- 99.48] pg/ml) than in the latter ([768. 83 +/- 146.96] pg/ml) (P < 0.05). CONCLUSION: Improved ELV can increase FSH and reduce InhB in rats, which may be associated with subfertility.

Intraosseous venous malformation of the maxilla after enucleation of a hemophilic pseudotumor: A case report.

BACKGROUND: Hemophilic pseudotumor (HP) is a rare complication in patients with hemophilia. The lesion most frequently occurs in the long bones, pelvis, small bones of the hands and feet, or rarely in the maxillofacial region. Postoperative changes in HP are seldom arrested, whereas angiogenesis characterized by disturbed wound healing in HP may cause vascular malformations. CASE SUMMARY: We report the case of an 11-year-old boy who was affected by maxillary intraosseous venous malformation. Enucleation of an HP without factor replacement was performed initially on the right side of the maxilla 3 years ago. The patient was referred to us because of painless swelling in the same location. Factor replacement and subtotal maxillectomy were performed. Pathological examinations revealed intraosseous venous malformation. CONCLUSION: This study is the first to document the development of intraosseous venous malformation after enucleation of an HP in the maxillofacial region. Angiogenesis characterized by disturbed wound healing in patients with hemophilia may be pivotal in the pathogenesis of this condition.

Silencing of lysyl oxidase­like 2 inhibits the migration, invasion and epithelial­to­mesenchymal transition of renal cell carcinoma cells through the Src/FAK signaling pathway.

The aim of the present study was to investigate the effects of lysyl oxidase­like 2 (LOXL2) on the invasion, migration and epithelial­to­mesenchymal transition (EMT) of renal cell carcinoma (RCC) cells through the steroid receptor coactivator (Src)/focal adhesion kinase (FAK) signaling pathway. RCC tissues and adjacent normal tissues were collected from 80 patients with RCC. Immunohistochemistry was used to determine the positive expression rate of the LOXL2 protein. The expression levels of LOXL2 in the HK­2, 786­O, ACHN, Caki1 and A498 cell lines were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The high LOXL2­expressing 786­O cells were selected for gene silencing experiments, whereas Caki1 cells, which exhibited low LOXL2 expression, were used for overexpression experiments. RT­qPCR and western blot analysis were applied to determine the expression of LOXL2, FAK, Src, matrix metalloproteinase (MMP)­9, epithelial (E)­cadherin, neuronal (N)­cadherin and vimentin. A MTT assay, a Transwell assay, a wound healing assay and flow cytometry were performed to detect cell proliferation, invasion, migration, cell cycle distribution and apoptosis, respectively. The protein expression rate of LOXL2 in RCC tissues was higher compared with that in adjacent normal tissues. Compared with adjacent normal tissues, the mRNA and protein expression levels of LOXL2, FAK, Src, MMP­9, N­cadherin and vimentin and the levels of FAK and Src phosphorylation were increased, while the mRNA and protein expression levels of E­cadherin were decreased in RCC tissues. Following the transfection of 786­O cells with small interfering (si) RNA against LOXL2, the mRNA and protein expression levels of FAK, Src, MMP­9, N­cadherin and vimentin and the levels of phosphorylated FAK and Src were notably decreased in the si­LOXL2 and PP2 inhibitor treated groups, while that of E­cadherin was substantially increased. Additionally, cell proliferation, invasion, migration and the percentage of RCC cells in the G1 phase were reduced, and cell apoptosis was increased. Additionally, Caki1 cells transfected with LOXL2 exhibited an opposite trend. In summary, these results indicate that LOXL2 silencing inhibits the invasion, migration and EMT in RCC cells through inhibition of the Src/FAK signaling pathway.

IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C.

Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.

Risk factors for erectile dysfunction in patients with urethral strictures secondary to blunt trauma.

INTRODUCTION: Erectile dysfunction (ED) is a well-known consequence of pelvic fracture, particularly in cases involving urethral injury. There are several risk factors that may be related to ED. However, no systemic approach is used to assess erectile function secondary to urethral trauma. AIM: To investigate ED associated with urethral injury secondary to pelvic fracture and perineal trauma. METHODS: Forty patients with traumatic urethral strictures secondary to blunt traumatic impact episode to the pelvis or perineum were included in our study. Pelvic fractures and urethral strictures were categorized according to injury types and radiological findings. All patients underwent nocturnal penile tumescence (NPT) monitoring, dynamic color-duplex Doppler ultrasonography (D-CDDU) before surgery. NPT monitoring was conducted again after surgery. MAIN OUTCOME MEASURES: The events of NPT and D-CDDU were recorded. RESULTS: In all patients, 11 had organic ED demonstrated by NPT. Vascular pathology was identified in three of 11 patients (27%). The peak systolic velocity of cavernosal artery was lower in patients with pubic diastasis in comparison to those without diastasis (P < 0.05). Significant changes in penile length and circumference were noted in posterior urethral injury compared with anterior urethral injury during erection (P < 0.05). The erectile duration time has a similar statistical difference in two groups mentioned above. However, no significant difference could be observed in the end-to-end anatomosis procedure before and after surgery (P > 0.05). CONCLUSIONS: The pelvic fracture type, especially pubic diastasis, is a risk factor for ED following urethral injury. Location of the stricture is also a risk factor for subsequent erectile dysfunction.