Objective:To study the expression and significance of gelsolin and cyclinD1 in epithelial ovarian tumors.Methods:The expression of gelsolin and cyclinD1 were detected by immunohistochemistry(S-P technique) in 65 cases of epithelial ovarian tumors,18 cases of ovarian borderline tumors and 24 normal ovarian tissue samples.Results:Expression of gelsolin in borderline tumors(33.3%) and malignant epithelial ovarian cancer(16.9%) were much lower than that in normal ovarian tissues(75.0%)(P0.01);however,there was no significant difference in the expression of gelsol between borderline tumor and malignant ovarian tumor(P0.05);The expression rates of cyclinD1 were respectively 38.9%,67.7%,and 8.3% in borderline tumor,malignant epithelial ovarian tumors and normal ovarian tissues,the differences were significant(P0.01,P0.05).The expression of gelsolin and cyclinD1 had no correlation with age,pathological features such as pathological type,histological differentiation and clinical stage(P0.05).Conclusions:The low expression of gelsolin and over expression of cyclinD1 may play an important role in the pathogenesis and progression of epithelial ovarian tumors,and might involve in the early stage of tumorigenesis.
Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear. This study aimed to elucidate the role of high mobility group box 1 (HMGB1) in NETs involved in the pathogenesis of PE. The concentration of NETs was detected in the plasma of patients with PE using enzyme-linked immunosorbent assay (ELISA). Placental samples were collected from patients with PE to detect the expression of HMGB1 through Western Blot and PCR. For in vitro experiments, human trophoblast HTR-8/SVneo cells were treated with NETs, and their proliferation, invasion, migration, and apoptosis ability; degree of oxidative stress; and secretion of inflammatory factors were detected. Compared with that in normal pregnant women, an increase in the release of NETs was observed in the peripheral blood of patients with PE. HMGB1 was increased in the placenta of PE patients and colocalized with NETs. The treatment of human trophoblast HTR-8/SVneo cells with NETs resulted in the inhibition of HTR-8/SVneo cell invasion and migration and increases in the release of reactive oxygen species (ROS), and several inflammatory factors (IL-1β, IL-6, IL-8, and TNF-α). These damaging effects can be reversed by the HMGB1 scavenger glycyrrhizin, which indicates that NETs can mediate trophoblast damage and the expression of several inflammatory factors through HMGB1. NETs can cause trophoblast inflammation-related functional damage through HMGB1 during the occurrence and development of preeclampsia. HMGB1 produces a marked effect in the PE cascade of oxidative stress involving NETs. Inhibiting HMGB1 to suppress NETs damage is a possible approach for the future treatment of PE.
Excessive deposition of extracellular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was undertaken to investigate the activity of matrix metalloproteinase-2 (MMP-2), the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in kidney tissues of diabetic rats, and to explore the degradative pathway of type IV collagen (IV-C) and the renal protective effects of ACE inhibition-benazepril.Twenty-four healthy male Wistar rats were divided randomly into normal control group (NC group), untreated diabetes mellitus group (DM group), and diabetes mellitus group treated with benazepril (DL group). The rat model of diabetes mellitus was induced by intraperitoneal injection of streptozocin (60 mg/kg). After the establishment of DM model, benazepril (10 mg.kg(-1).d(-1)) was given to the DL group for 12 weeks, and the same volume of water was given to the other two groups. At the end of 12 weeks, renal function was evaluated with 24-hour urinary protein (Upro), clearance of creatinine (Ccr), and blood urea nitrogen (BUN). MMP-2 activity was determined by gelatin zymography. The levels of MMP-2, TIMP-2 and collagen IV (IV-C) protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-2 and TIMP-2 was measured by reverse transcription polymerase chain reaction (RT-PCR).The levels of BUN, Upro and Ccr in the DM group were higher than those in the NC group. In the DM group, the mRNA, enzymatic activity and proteins of MMP-2 decreased, but the expressions of IV-C and TIMP-2 increased. All diabetes-associated changes in renal function and MMP/TIMP were attenuated after benazepril treatment with reduced IV-C accumulation.The changes of MMP-2 and TIMP-2 expressions in kidney tissues of diabetes rats may contribute to the occurrence and progression of diabetic nephropathy. Benazepril could exert protective effects on diabetic nephropathy, owing to the upregulation of MMP-2 and downregulation of TIMP-2 expressions, which further inhibits the excessive deposition of extracellular matrix in the glomerulus.
The present study was designed to explore the roles of MMP-2/TIMP-2 in cardiac fibrosis and to study the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI) on cardiac remodelling in streptozotocin(STZ)-induced diabetic rats.Male Wistar rats were randomly divided into three groups: a normal control group (NC), a diabetes mellitus-untreated group (DM) and a diabetes mellitus benazepril-treated group (DB). Diabetes mellitus was induced in the DM and DB groups by intraperitoneal injection of streptozotocin (60 mg/kg). DB rats were treated with benazepril 10 mg/kg/day for 12 weeks by remedial perfusing of the stomach. In the DM group, compared with the NC group, the gene and protein expression of MMP-2 decreased while the TIMP-2 gene and protein expression increased in heart tissues, along with a markedly cardiac collagen deposition.All the above changes were attenuated by benazepril treatment in the DB group.The imbalance of MMP-2 and TIMP-2 expressions in heart tissues might participate in interstitial fibrosis in diabetic myocardiopathy. Benazepril may ameliorate cardiac fibrosis partly by regulating the MMP-2/TIMP-2 system.
Objective:To assess the technical feasibility of sigmoid colon vaginoplasty in patients with Mayer-Rokitansky-Kuster-Hauser(MRKH) syndrome.Methods: 32 patients with MRKH syndrome underwent sigmo-id colon vaginoplasty.The operative technique and the operation complications,the anatomical and functional results of the neovagina were evaluated.Results: The mean operation duration was 156 min(range 130～180 min).The mean fall of haemoglobin was 20 g/L(range 15~33 g/L).The complications included rectal injury(n=1),urinary tract infection(n=1),infection in incision wound(n=1).The mean hospital stay was 10.6 d(range 9~22 d).The mean length of neovagina was 10.7 cm(range 10~12 cm) and the width was about 4 cm.There was an obvious decrease of the discharge and stink of neovagina in the initial 6 months.The patients with regular intercourse achieved satisfaction in half a year or one year after operation.Conclusion: sigmoid colon vaginoplasty is an effective approach MRKH syndrome.
Hyperinsulinemia and insulin resistance are present in the majority of women with polycystic ovary syndrome (PCOS). Both metformin and rosiglitazone can improve the ovulation and endocrine disorders of the patients. How about the combination of the two? It is rarely reported. This study aimed to compare the therapeutic efficacy of metformin versus metformin plus rosiglitazone in patients with PCOS.Fifty-eight women with PCOS were randomly assigned to two groups. Metformin group (29) was treated with metformin mono-therapy and metformin plus rosiglitazone group (29) was treated with metformin plus rosiglitazone for 6 months. Treatment was discontinued once pregnancy was diagnosed.Fasting insulin, postprandial insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), triglyceride, lower density cholesterol and testosterone level decreased significantly in both groups (P < 0.05). Metformin plus rosiglitazone had a better effect than metformin mono-therapy. Body mass index decreased by 7.8% in metformin group while no significant change in metformin plus rosiglitazone group. There were eight pregnancies, six in metformin plus rosiglitazone group (one abortion) and two in metformin group. There was no congenital anomaly at birth and seven infants developed well at one year's follow-up.Metformin can improve insulin resistance and imbalance of endocrine hormones. Metformin plus rosiglitazone has a more pronounced therapeutic effect and achieved more pregnancies than mono-therapy with metformin. The use of metformin and rosiglitazone before pregnancy has no obvious side effect on the development of the infants. Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.
The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells.Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16.Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis.Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.
To the editor: Renal cell carcinoma (RCC) is a malignant kidney tumor that originates from renal tubular epithelial system, and 30% of patients with RCC have metastasis at the time of initial diagnosis.1 Frequent sites of RCC metastases include lung, regional lymphatic nodes, liver, bone, and brain,2 while vaginal metastasis of RCC was extremely rare and mostly occurred in the left kidney. We reported a rare case of a patient with metastatic RCC to vagina and investigated the symptoms, diagnosis, therapies, and possible metastatic mechanisms. A 22-year-old female patient was admitted to the urological surgical department of Fujian medical university affiliated hospital with gross hematuria for 10 days. The physical examination revealed the presence of a mass sized 13.5 cm × 9.0 cm with median quality, clear boundary, and poor motility in the right lower abdomen. The girl had female pubic hair distribution and no abnormal secretion was noted outside the vagina and urethra. Magnetic resonance imaging (MRI) of the abdomen and pelvis showed the right RCC (Figure 1A), and the ultrasound was performed to reveal a right renal tumor sized about 13 cm × 9 cm. The patient underwent right radical nephrectomy and Fuhrman Grade 2 RCC was revealed during the operation. Pathological examination showed clear cell subtype.Figure 1.: MRI examination and histopathological results. A: Preoperative MRI showed right RCC sized about 13.5 cm × 9.0 cm. No abnormal condition was noted in the contralateral kidney. B: Pathological analysis showed neoplastic tissues underlying vaginal mucosa (HE staining, original magnification ×400).After surgery, the patient was followed up with systematic urological examinations, including serum chemistry studies, chest radiographs, and computed tomography (CT) of the abdomen and pelvis. Eight months after the operation, she was admitted to the department of gynecology in Shandong provincial hospital with irregular vaginal bleeding for 3 months. Vaginal tumor was noted by ultrasound and MRI examinations. The tumor, sized 4 cm × 3 cm and irregular patterns, lied in the posterior wall of the vagina, 2 cm proximal to the vaginal orifice. Tumor excision was performed under spinal anesthesia and subsequent pathological examination demonstrated metastatic adenocarcinoma. Considering the clinical history and immunohistochemical study, the tumor was thought to be primary renal carcinoma. The pathological study presented clear cell carcinoma, Fuhrman Grade 2 (Figure 1B). Clinical history and histopathological results supported the diagnosis of metastatic vaginal lesion of primary RCC. No other metastatic focus was noted. After surgery, the girl was treated with Sutent (Sunitinib malate), a novel molecular-targeted medicine applied to advanced tumors with distant metastasis. Sutent was regarded as a postoperative therapy and the recommended dose was one 50 mg oral dose once daily on a schedule of 4 weeks on treatment followed by 2 weeks off treatment. Dose increase or reduction of 12.5 mg increments was recommended based on individual safety and tolerability. No local relapse or distant metastasis was founded 2 months after the vaginal lesion excision. Literature revealed that most cases of RCC with vaginal metastasis took place in the left kidney carcinomas and the dissemination usually occurred in the left wall of the vagina.3 The angiography demonstrated that the retrograde flow is from the left renal vein to the ovarian vein and uterovaginal plexus,4 so the reproductive vein (ovarian vein) reflux has always been considered to be the main dissemination route.
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