[Molecular mechanisms of androgens regulating the eNOS expression in rat corpus cavernosum].

OBJECTIVE: To investigate whether androgens can regulate the expression of eNOS in rat corpus cavernosum through AKT3, PIK3CA, CALM, and CAV1 and influence erectile function. METHODS: Thirty-six 8-week-old male SD rats were randomly divided into groups A (4-week control), B (6-week control), C (4-week castration), D (6-week castration), E (4-week castration + testosterone replacement), and F (6-week castration + testosterone replacement). Both the testis and epididymis were removed from the rats in groups C, D, E and F, and on the second day after surgery, the animals of groups E and F were subcutaneously injected with testosterone propionate at 3 mg per kg of the body weight qd alt while all the others with isodose oil instead. At 4 weeks (for groups A, C and E) and 6 weeks (for groups B, D and F) after treatment, we detected the maximum intracavernous pressure (ICPmax), the mean carotid arterial pressure (MAP) and their ratio (ICPmax/MAP), measured the level of serum testosterone (T), and determined the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 in the corpus cavernosum by Western blot and immunohistochemistry. RESULTS: No statistically significant differences were observed in the body weight and MAP among different groups. The serum T level and ICPmax/MAP were remarkably lower in groups C and D than in the other four groups (P<0.01) as well as in groups E and F than in A and B (P<0.05) but exhibited no significant differences either between E and F or between A and B. Immunohistochemistry showed that eNOS and P-eNOS were mainly expressed in the vascular endothelial cell membrane and cavernous vascular lumen, while AKT3, PIK3CA, CALM and CAV1 chiefly in the vascular endothelial cell cytoplasm and membrane, with a few in the smooth muscle cells. Western blot analysis manifested that the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 were markedly lower in groups C and D than in A, B, E and F (P<0.01) as well as in D than in C (P<0.05) but those in groups E and F did not showed any significant difference from those in A and B, nor E from F or A from B. CONCLUSIONS: Androgens can improve erectile function by upregulating the expressions of AKT3, PIK3CA, CALM and CAV1 protein molecules and activating eNOS after its phosphorylation, though the exact molecular mechanisms are yet to be further studied.

Periosteal osteosarcoma and Marfan's syndrome: A case report and literature review.

Periosteal osteosarcoma (POS) is a rare primary malignant bone tumor arising from the surface of long bones. In addition, Marfan's syndrome (MFS) is an infrequent hereditary autosomal dominant connective tissue disorder with high penetrance and variable phenotypes, which primarily affects the ocular, skeletal and cardiovascular systems. The present study reported a case of POS and MFS co-occurring in a child. A 6-year-old girl with MFS presented with pain, swelling and deformity in the right thigh following a fall. The patient was diagnosed with a right femoral shaft fracture and underwent open internal fixation surgery at a local hospital. At 2 weeks following surgery, the patient's parents observed increased swelling in the right thigh and thus, revisited the clinic. X-ray examination revealed extensive osteotylus around the fracture site and the clinician decided to remove the internal fixation. Following removal of the implant, aggravated swelling and superficial venous engorgement were observed. The patient was then admitted to Nanfang Hospital, where magnetic resonance imaging was performed, which identified symptoms of an abnormal periosteal reaction with bone erosion, indicating POS. The patient underwent a wide resection of the tumor and the histopathological examination confirmed the diagnosis of POS. No recurrence was identified at 9 months postoperatively. In conclusion, the present case report may result in increased awareness of the possibility of malignant bone tumors in a hereditary patient with osteotylus overgrowth following fracture surgery; in addition, the present case indicated a possible correlation between POS and MFS.

Clinical Characteristics and Treatment of Extremity Chronic Osteomyelitis in Southern China: A Retrospective Analysis of 394 Consecutive Patients.

Although extremity chronic osteomyelitis is common in China, updated data were still limited regarding its characterizations. The present study aimed to review clinical features of extremity chronic osteomyelitis in Southern China.A retrospective analysis was conducted in the patients who had sought medical attention from January 2010 to April 2015 for extremity chronic osteomyelitis in Nanfang Hospital in Southern China. Clinical data were collected and analyzed.A total of 394 patients (307 males and 87 females) were included, giving a gender ratio of 3.53. The median age at first diagnosis was 42 years for all. The most frequent type was traumatic osteomyelitis (262 cases, 66.50%), which was mainly caused by open injury (166 cases, 63.36%) and during a road accident (91 cases, 34.73%). Single-site infection accounted for 81.98% (323 cases), with tibia (126 cases), femur (79 cases), calcaneus (37 cases), and toes (37 cases) as the top sites. The positive rate of intraoperative culture was 70.63% (214/303), 78.97% (169/214) of which was monomicrobial infection. Staphylococcus aureus (59 cases) was the most frequent bacteria for monomicrobial infection, followed by Pseudomonas aeruginosa (29 cases) and Escherichia coli (11 cases). The positive ratios of preoperative serum white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were 21.63%, 64.92%, 53.27%, 42.25%, 72.82%, and 66.67%, respectively. The most frequently used intravenous antibiotic was cephalosporins. The overall cure rate was 77.74%, with a total amputation rate of 16.75%.In this representative Chinese cohort, extremity chronic osteomyelitis was mostly caused by open injury and during a road accident, predominated in males and favored the tibia. S. aureus was the most frequent pathogenic organism. Preoperative elevated levels of serum IL-6, TNF-α, and ESR may be helpful diagnostic indicators of the disease. Most patients achieved a favorable clinical efficacy after appropriate treatment.

Pigmented villonodular synovitis: a retrospective multicenter study of 237 cases.

PURPOSE: To review clinical characteristics of pigmented villonodular synovitis (PVNS) in China. METHODS: Electronic medical records (EMR) of four Chinese institutes were queried for patients with histologically proven PVNS between January 2005 and February 2014. Their data were collected including gender, age at diagnosis, clinical presentation, affected site, symptom duration, comorbidities, treatment strategy, recurrence and routine laboratories. RESULTS: A total of 237 patients with biopsy-proven PVNS were investigated. The gender ratio was 1.35 for a female predominance (101 males and 136 females). The average age was 36 years (range, 2 to 83 years). The median delay from initial clinical symptom to diagnosis was 18 months. Main affected areas were the knee (73.84%) and the hip (18.14%). Forty patients had a clear history of joint trauma. Six patients were concurrently diagnosed with PVNS and avascular necrosis (AVN). Five patients suffered from PVNS following implantation of orthopaedic devices including artificial prosthesis, plate and wire. One hundred and twenty-nine patients underwent arthroscopic synovectomy and 108 open synovectomy. Altogether 48 patients (26 males and 22 females) had recurrence of disease. The relapse rate was 24% (knee) and 6.98% (hip), 20.93% (open surgery) and 19.44% (arthroscopy), respectively. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) rate were elevated in 45.83% and 38.41% of the patients respectively. CONCLUSIONS: To our knowledge, this study is the largest sample size of PVNS patients reported as well as the largest sample of PVNS with concurrent AVN reported to date. Our outcomes suggest that PVNS shows a female predominance, occurs mostly between 20-40 years and favors the knee and hip. Recurrence is frequent, particularly in the knee. Serum ESR and CRP may be elevated in some patients. Additionally, the present study supports the theory of an association between PVNS and orthopedic surgery, which is not limited to joint replacement.

Eucommia ulmoides Oliv. bark aqueous extract inhibits osteoarthritis in a rat model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. bark (EU) is a common traditional Chinese herbal medicine for treatment of osteoarthritis (OA), but its therapeutic effect on OA and the underlying mechanisms have not been fully clarified. Our previous study showed that Eucommia ulmoides Oliv. bark aqueous extract (EUE) had a protective effect on cartilage, and this study was aimed to investigate the anti-osteoarthritis effect and mechanisms of EUE in a rat model of osteoarthritis. MATERIALS AND METHODS: Thirty-two 5-week-old specific pathogen-free Sprague-Dawley rats which were randomized into four even groups (n=8). Group A received sham operation while the OA model was established using the modified Hulth technique in groups B, C and D. For eight weeks after operation, in addition to routine feeding, group A received gavage with deionized water, group B with deionized water, group C with 1.35 g/kg/day EUE, and group D with 2.7 g/kg/day EUE. Eight weeks postoperatively, all of the animals were euthanized for radiological, gross and histopathological observations to evaluate the effect of EUE on OA and to determine its potential mechanisms. RESULTS: Radiological and histopathological observations showed that the articular degenerative changes were significantly more alleviated in groups C and D than in group B, while there were no obviously degenerative manifestations in group A. Mankin׳s scores in groups C and D were significantly lower than in group B (P<0.01). The severity of OA was significantly less in group D than in group C (P<0.01). The IL-1ß and IL-6 contents in serum and MMP-3 secretion in articular cartilage were significantly lower in groups C and D than those in group B (P<0.01), and significantly lower in group D than those in group C (P<0.01). Compared with group B, phosphorylated Akt was significantly down-regulated in groups C and D. CONCLUSIONS: EUE may inhibit the progression of osteoarthritis by inhibiting the PI3K/Akt pathway to delay cartilage degeneration, reduce inflammatory cytokines and prevent MMP-3 secretion. Therefore, EU is a potential therapeutic agent for OA, but its efficacy is limited.

[Non-coding RNAs in castration-resistant prostate cancer].

Non-coding RNAs (ncRNAs) are a large class of RNA molecules that do not encode proteins, regulate gene expressions multifacetedly, and influence the metabolism, proliferation, differentiation and apoptosis of cells as well as the occurrence and progression of tumors. Some of the ncRNAs act as cancer genes, such as miR-19a, miR-125b, miR-616, miR-7, miR-221, MALAT-1, and PRNCR1, which are upregulated in castration-resistant prostate cancer (CRPC) tissues or cell lines, and promote the development and progression of CRPC, some act as tumor suppressor genes, including miR-185, miR-342, miR-15, miR-16, and miR-146, which are downregulated in CRPC tissues or cell lines and inhibit or delay the occurrence of CRPC, and still others, such as miR-7, miR-19a, miR-125b, miR-221, and MALAT-1, are differentially expressed in the serum or tissue and can be used as potential biomarkers for the early diagnosis and prognosis of CRPC. This article presents an overview on the roles of ncRNAs in the occurrence, progression, diagnosis, and prognosis of CRPC and advances in their studies.