Outbreak investigation of Serratia marcescens bloodstream infection in an obstetric ward for high-risk pregnant women.

BACKGROUND: Serratia marcescens is a gram-negative bacterium that is widespread in the environment. S. marcescens bacteremia can be fatal during pregnancy and cause persistent chorioamnionitis. This study reports an outbreak of Serratia marcescens bloodstream infection (BSI) among high-risk pregnant women in an obstetric ward. The purpose of this study is to report our experience with the usefulness of the ATP test in hospital environmental management and to confirm that bloodstream infections of patients with the same strain were correlated by WGS testing. METHODS: This retrospective study collected the data of inpatients with S. marcescens bacteremia in obstetric ward for high-risk pregnant women from August 22, 2021, to October 14, 2021. We performed: an adenosine triphosphate (ATP) bioluminescence test in the environment with a high-contact area; environmental culture; on-site monitoring and staff education; and whole-genome sequencing (WGS) to evaluate genetic relationships among S. marcescens isolates. RESULTS: S. marcescens BSI occurred in four consecutive patients. None of the patients had central venous catheters. An ATP bioluminescence test revealed that high-contact areas and areas for injection preparation were not clean (≥ 1000 relative light units). However, S. marcescens was not identified in the environmental cultures, likely due to intensive environmental cleaning and discarding of potentially contaminated specimens before the culture test. On-site monitoring and education were conducted for 1 month. There were no further reports of BSI until 6 months after the last patient was discharged. WGS performed on three isolates from three patients indicated that the isolated S. marcescens was likely from the same strain. CONCLUSIONS: We controlled an S. marcescens outbreak by improving environmental cleaning as well as education of and behavior changes in healthcare workers. Using the ATP bioluminescence test can provide feedback on environmental cleaning and education. WGS played a role in determining the spread of BSI caused by the same strain.

Hepatocyte-specific deletion of Bis causes senescence in the liver without deteriorating hepatic function.

Bcl-2-interacting cell death suppressor (BIS), also called as BAG3, regulates numerous physiological processes, such as apoptosis, protein quality control, and senescence. Whole-body Bis-knockout (KO) mice exhibit early lethality following cardiac and skeletal muscle dysfunction. The first attempt to generate organ-specific knockout mice resulted in constitutive or inducible heart-specific Bis-knockout mice, which exhibited cardiac dilation and underwent premature death. Here, we generated hepatocyte-specific Bis-knockout (Bis-HKO) mice and found no abnormalities in metabolic function and survival. However, depletion of HSPB8 and accumulation of p62 indicated impaired autophagy in Bis-HKO livers. Interestingly, the number of peroxisomes wrapped by phagophore membranes increased as evidenced by transmission electron microscopy analysis, indicating defects in the progression of pexophagy. In addition, increased dihydroethidine intensities and histone H3 K9me3-positive nuclei indicated increased oxidative stress and senescence induction in Bis-HKO livers. Mechanistically, p27 was upregulated in Bis-HKO livers. In SNU368 hepatocellular carcinoma cells, BIS depletion led to p27 upregulation, and increase in histone H3 K9me3 levels and senescence-associated ß-galactosidase staining; therefore, reproducing the in vivo senescence phenotype. Despite the observation of no metabolic abnormalities, BIS depletion led to defective autophagy, increased oxidative stress, and senescence in Bis-HKO livers. Collectively, our results suggest a role for BIS in maintaining liver regeneration potential under pathological conditions.

Spontaneous reduction of transvaginal small bowel evisceration after abdominal hysterectomy for cervical cancer: A case report.

RATIONALE: Transvaginal evisceration of the small bowel is an extremely rare condition after hysterectomy, which requires urgent surgical intervention to prevent serious bowel morbidity and mortality. PATIENT CONCERNS: A 65-year-old woman presented with sudden-onset severe abdominal pain and a mass protruding through the vagina. The past surgical history was significant, with an abdominal hysterectomy for cervical cancer performed 11 weeks prior to presentation. DIAGNOSIS: Pelvic examination revealed prolapsed small-bowel loops (18-20 cm in length). Pelvic computed tomography scan confirmed the presence of transvaginal evisceration of the small bowel. INTERVENTIONS: Bowel reduction and urgent laparotomy were the selected treatment approaches for a detailed inspection and thorough washing of the intrα-abdominal cavity. A Foley catheter was inserted in the emergency room, with the subject in the lithotomy position. The prolapsed bowel loops spontaneously reduced without manual reduction, and the vault defect was repaired transvaginally. OUTCOMES: The patient experienced no postoperative complications and remained disease-free for 9months postoperatively. LESSONS: Transvaginal evisceration of the small bowel should be considered a surgical emergency. A multidisciplinary approach to prompt case management involving clinicians in gynecology, general surgery, and emergency medicine is vital for preventing serious consequences. Hysterectomy is the most frequently performed gynecological surgical procedure, and evisceration occurs most often after hysterectomy. Therefore, patients should be informed about this rare but possible hysterectomy complication.

Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis.

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.

Successful treatment of locally advanced bulky cervical cancer complicated by irreducible complete uterine prolapse: A case report.

RATIONALE: Cervical cancer complicated by irreducible complete uterine prolapse in elderly patients is extremely rare. No standard treatment has been established for these conditions. PATIENT CONCERNS: A 74-year-old woman with a 30-year history of pelvic organ prolapse presented with irreducible complete uterine prolapse and a large exophytic mass involving the cervix and vaginal wall. DIAGNOSIS: Biopsy of the mass was performed at the referring institution and showed invasive verrucous-type squamous cell carcinoma. INTERVENTIONS: A prolapsed uterus with a tumor mass could not be manually reduced. After completion of concurrent chemoradiotherapy, the tumor mass in the prolapsed uterus decreased and could be reduced manually. Subsequently, the patient underwent hysterectomy and intra-abdominal uterosacral ligament suspension. OUTCOMES: At 19 months of postoperative follow-up, the patient remained disease-free and had no evidence of vault prolapse. LESSONS: This study has important clinical implications and may provide a therapeutic strategy to address unmet medical needs in combination with locally advanced cervical cancer complicated by irreducible complete uterine prolapse. These conditions were successfully treated using a multidisciplinary approach of chemoradiotherapy followed by radical hysterectomy and uterosacral ligament suspension.

Protective Effects and Benefits of Olive Oil and Its Extracts on Women's Health.

Women and men share similar diseases; however, women have unique issues, including gynecologic diseases and diseases related to menstruation, menopause, and post menopause. In recent decades, scientists paid more attention to natural products and their derivatives because of their good tolerability and effectiveness in disease prevention and treatment. Olive oil is an essential component in the Mediterranean diet, a diet well known for its protective impact on human well-being. Investigation of the active components in olive oil, such as oleuropein and hydroxytyrosol, showed positive effects in various diseases. Their effects have been clarified in many suggested mechanisms and have shown promising results in animal and human studies, especially in breast cancer, ovarian cancer, postmenopausal osteoporosis, and other disorders. This review summarizes the current evidence of the role of olives and olive polyphenols in women's health issues and their potential implications in the treatment and prevention of health problems in women.

The Expression and Contribution of SRCs with Preeclampsia Placenta.

The steroid hormones act by binding to their receptors and subsequently interacting with coactivators. Several classes of coactivators have been identified and shown to be essential in estradiol (E2) responsiveness. The major coregulators are the p160 steroid receptor coactivator (SRC) family. Although the function of SRCs in other organs has been well studied, it has not been thoroughly studied in the placenta. In addition, the correlation between preeclampsia (PE) and SRCs has not been examined previously. Therefore, we compared the expression patterns of SRCs in normal and PE placentas. In human PE placental tissues, SRC-1 mRNA, and protein levels were downregulated in the PE group. In addition, to assess the expression of SRCs in a PE environment, we used Reduced Uterine Perfusion Pressure (RUPP) model and placental cells were cultured in hypoxia condition. SRC-1 proteins were reduced in the placenta of PE-like rat RUPP model. Furthermore, SRCs proteins were significantly downregulated in hypoxia-grown placental cells. To examine the interaction between estrogen receptors (ERs) and SRC-1 protein, we performed co-immunoprecipitation. The interaction of SRC-1 with ERα was significantly stronger than that with ERß. In PE placenta, the interaction of both ERα and ERß with SRC-1 was stronger than that in normal placenta. In summary, our results demonstrate that expression levels of SRC-1, not SRC-2 and SRC-3, were decreased in hypoxia-induced PE placenta, which may further reduce the signaling of sex steroid hormones such as E2. The dysregulated signaling of E2 by SRC-1 expression could be associated with the PE placental symptoms of patients.

Enzyme-Aided Extraction of Fucoidan by AMG Augments the Functionality of EPCs through Regulation of the AKT/Rheb Signaling Pathway.

The purpose of the present study is to improve the endothelial progenitor cells (EPC) activation, proliferation, and angiogenesis using enzyme-aided extraction of fucoidan by amyloglucosidase (EAEF-AMG). Enzyme-aided extraction of fucoidan by AMG (EAEF-AMG) significantly increased EPC proliferation by reducing the reactive oxygen species (ROS) and decreasing apoptosis. Notably, EAEF-AMG treated EPCs repressed the colocalization of TSC2/LAMP1 and promoted perinuclear localization of mTOR/LAMP1 and mTOR/Rheb. Moreover, EAEF-AMG enhanced EPC functionalities, including tube formation, cell migration, and wound healing via regulation of AKT/Rheb signaling. Our data provided cell priming protocols to enhance therapeutic applications of EPCs using bioactive compounds for the treatment of CVD.

MHY2233 Attenuates Replicative Cellular Senescence in Human Endothelial Progenitor Cells via SIRT1 Signaling.

Cardiovascular diseases (CVDs) are a major cause of death worldwide. Due to the prevalence of many side effects and incomplete recovery from pharmacotherapies, stem cell therapy is being targeted for the treatment of CVDs. Among the different types of stem cells, endothelial progenitor cells (EPCs) have great potential. However, cellular replicative senescence decreases the proliferation, migration, and overall function of EPCs. Sirtuin 1 (SIRT1) has been mainly studied in the mammalian aging process. MHY2233 is a potent synthetic SIRT1 activator and a novel antiaging compound. We found that MHY2233 increased the expression of SIRT1, and its deacetylase activity thereby decreased expression of the cellular senescence biomarkers, p53, p16, and p21. In addition, MHY2233 decreased senescence-associated beta-galactosidase- (SA-ß-gal-) positive cells and senescence-associated secretory phenotypes (SASPs), such as the secretion of interleukin- (IL-) 6, IL-8, IL-1α, and IL-1ß. MHY2233 treatment protected senescent EPCs from oxidative stress by decreasing cellular reactive oxygen species (ROS) levels, thus enhancing cell survival and function. The angiogenesis, proliferation, and migration of senescent EPCs were enhanced by MHY2233 treatment. Thus, MHY2233 reduces replicative and oxidative stress-induced senescence in EPCs. Therefore, this novel antiaging compound MHY2233 might be considered a potent therapeutic agent for the treatment of age-associated CVDs.

Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage.

Angiogenesis plays a critical role in embryo development, tissue repair, tumor growth and wound healing. In the present study, we investigated the role of the serine/threonine kinase Akt in angiogenesis. Silencing of Akt1 in human umbilical vein endothelial cells significantly inhibited vascular endothelial growth factor (VEGF)-induced capillary-like tube formation. Mice lacking Akt1 exhibited impaired retinal angiogenesis with delayed endothelial cell (EC) proliferation. In addition, VEGF-induced corneal angiogenesis and tumor development were significantly inhibited in mice lacking Akt1. Loss of Akt1 resulted in reduced angiogenic sprouting, as well as the proliferation of ECs and mural cells. Addition of culture supernatant of vascular smooth muscle cells (VSMCs) in which Akt1 was silenced suppressed tube formation, the stability of preformed tubes and the proliferation of ECs. In addition, attachment of VSMCs to ECs was significantly reduced in cells in which Akt1 was silenced. Mural cell coverage of retinal vasculature was reduced in mice lacking Akt1. Finally, mice lacking Akt1 showed severe retinal hemorrhage compared to the wild-type. These results suggest that the regulation of EC function and mural cell coverage by Akt1 is important for blood vessel maturation during angiogenesis.

Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of ß2-Adrenergic Receptor.

Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.

Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities.

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

Amniotic fluid index, single deepest pocket and transvaginal cervical length: Parameter of predictive delivery latency in preterm premature rupture of membranes.

OBJECTIVE: Prediction of delivery latency complicated with preterm premature rupture of membrane (PPROM) is crucial for reducing maternal and neonatal complications. Therefore, we investigated the correlations between latency period and cut-off values of ultrasonographic parameters, ultimately predicting delivery latency. MATERIALS AND METHODS: The retrospective study was performed on 121 PPROM patients enrolled between March 2010 and July 2015. Parameters including amniotic fluid index (AFI), single deepest pocket (SDP) and transvaginal cervical length (TVCL) were measured in 99 singleton pregnancies with PPROM. Latency was defined as the period from sonographic measurements to delivery day. The parameters were analyzed independently by Wilcoxon rank sum test and Fisher's exact test. Cut-off values were determined using a receiver operating characteristic (ROC) curve. RESULTS: In delivery latency within 3 days, AFI and SDP were decreased with significantly shorter TVCL. AFI and SDP had the highest sensitivity (82.2%) and SDP combined with TVCL showed the highest specificity (75.9%) in area under curve (AUC) value. The predicted median latency period was less than 2 days within the cutoff value of parameter (AFI ≤ 7.72, SDP ≤ 3.2 and TVCL ≤ 1.69). CONCLUSION: AFI and SDP combined with TVCL could be useful predictive parameters of the latency interval from PPROM to delivery.

Leptin, leptin receptors and hypoxia-induced factor-1α expression in the placental bed of patients with and without preeclampsia during pregnancy.

The mechanism underlying the pathogenesis of preeclampsia (PE) has been previously investigated but remains to be elucidated. Among numerous biomarkers that are associated with the pathogenesis of PE, leptin is most frequently investigated. Although studies concerning the association between PE and the expression of leptin in the serum and placenta have been conducted, the results are conflicting and inconsistent. Furthermore, the expression of leptin and its receptors in the placental bed and their association with PE, to the best of our knowledge, has not been previously reported. Therefore, to determine the association between the expression of leptin and its receptor, and pathogenesis and onset period of PE, placental bed tissues were obtained from cesarean section deliveries. The mRNA and protein expression levels of leptin and its receptor were investigated in normal pregnancies (n=18), pregnancies complicated with early­onset PE (n=9) and late­onset PE (n=9) by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the mRNA and protein expression of leptin in the placental bed was significantly increased in the PE groups compared with normal controls and was associated with the onset period of PE. Furthermore, as evidenced by immunostaining, leptin was upregulated in endothelial cells of the placental bed in the PE groups, with a particularly strong upregulation in activated endothelial cells from patients with early­onset PE. The results of the present study indicate that altered expression of leptin in the placental bed may contribute to the pathogenesis of PE.

Cosmetic outcomes of cesarean section scar; subcuticular suture versus intradermal buried suture.

OBJECTIVE: The objective of the study was to compare cosmetic outcomes and overall satisfaction rate of cesarean section scar between conventional subcuticular suture and intradermal buried vertical mattress. METHODS: Patients were enrolled to the study by chart review. A scar assessment was obtained retrospectively through a telephone survey. The patient component of the patient and observer scar assessment scale (POSAS) was utilized along with the overall satisfaction of the patient regarding their cesarean section scar and their willingness to choose the same skin closure technique when anticipating their next cesarean section. RESULTS: A total of 303 cases of cesarean section was recruited, 102 finished telephone surveys were calculated for the analyses. Subcuticular suture was regarded as control group (n=52) and intradermal buried suture as test group (n=50). The PSAS score of the test group (mean, 21.8) was lower than that of the control group (mean, 28), with a statistical significance (P=0.02). Overall satisfaction rate did not differ between the two groups. Two parameters of the PSAS score and the level of overall satisfaction showed significant correlation (Pearson's r, -0.63; P<0.01). CONCLUSION: We suggested the use of intradermal buried vertical mattress as a cosmetically superior skin closure method for application in cesarean sections over subcuticular stitch.

Feasibility of Immediate in-Intensive Care Unit Pulmonary Rehabilitation after Lung Transplantation: A Single Center Experience.

BACKGROUND: Physical function may influence perioperative outcomes of lung transplantation. We investigated the feasibility of a pulmonary rehabilitation program initiated in the immediate postoperative period at an intensive care unit (ICU) for patients who underwent lung transplantation. METHODS: We retrospectively evaluated 22 patients who received pulmonary rehabilitation initiated in the ICU within 2 weeks after lung transplantation at our institution from March 2015 to February 2016. Levels of physical function were graded at the start of pulmonary rehabilitation and then weekly throughout rehabilitation according to criteria from our institutional pulmonary rehabilitation program: grade 1, bedside (G1); grade 2, dangling (G2); grade 3, standing (G3); and grade IV, gait (G4). RESULTS: The median age of patients was 53 years (range, 25 to 73 years). Fourteen patients (64%) were males. The initial level of physical function was G1 in nine patients, G2 in seven patients, G3 in four patients, and G4 in two patients. Patients started pulmonary rehabilitation at a median of 7.5 days (range, 1 to 29 days) after lung transplantation. We did not observe any rehabilitation-related complications during follow-up. The final level of physical function was G1 in six patients, G3 in two patients, and G4 in 14 patients. Fourteen of the 22 patients were able to walk with or without assistance, and 13 of them maintained G4 until discharge; the eight remaining patients never achieved G4. CONCLUSIONS: Our results suggest the feasibility of early pulmonary rehabilitation initiated in the ICU within a few days after lung transplantation.

Prognostic value of preoperative lymphocyte-monocyte ratio in elderly patients with advanced epithelial ovarian cancer.

OBJECTIVE: To investigate the prognostic significance of preoperative lymphocyte-monocyte ratio (LMR) in elderly patients with advanced epithelial ovarian cancer (EOC) receiving primary cytoreductive surgery and adjuvant platinum-based chemotherapy. METHODS: A total of 42 elderly patients (≥65 years) diagnosed with EOC who are receiving primary cytoreductive surgery and adjuvant platinum-based chemotherapy from 2009 to 2012 was included. LMR was calculated from complete blood cell count sampled before operation. Receiver operating characteristic (ROC) curves were used to calculate optimal cut-off values for LMR. Prognostic significance with respect to overall survival (OS) and progression-free survival (PFS) were determined using log-rank test and Cox regression analysis. RESULTS: The optimized LMR cut-off value determined by ROC curve analysis was 3.63 for PFS and OS. The high LMR group (LMR ≥3.63) was found to be significantly more associated with optimal debulking (P=0.045) and platinum response (P=0.018) than the low LMR group. In addition, Kaplan-Meier analysis revealed the LMR-high group was significantly more associated with high PFS and OS rates (P=0.023 and P=0.033, respectively), and univariate analysis revealed that a high LMR, histology type, and optimal debulking and platinum responses were significantly associated with prolonged PFS and OS. However, subsequent Cox multivariate analysis showed only optimal debulking and platinum response were independent prognostic factors of PFS or OS. CONCLUSION: This study suggests that LMR might be associated with treatment and survival outcomes in elderly patients with EOC receiving standard oncology treatment.

Peptide YY producing strumal carcinoid tumor of the ovary in a postmenopausal woman: a rare cause of chronic constipation.

Strumal carcinoid tumor of the ovary is a rare subtype of ovarian carcinoid tumors; it is characterized by an intimate mixture of thyroid and carcinoid tissues. We present a case of a 64-year-old woman who presented with the chief complaint of persistent, severe constipation for over 5 years; she was later found to have an ovarian strumal carcinoid tumor. Computed tomography showed a well-defined solid mass measuring 6.4 cm at the right adnexa. The patient underwent right salpingo-oophorectomy and was histopathologically diagnosed as having a strumal carcinoid tumor. Immunohistochemical examination showed immunoreactivity for peptide YY (PYY), which exerts an inhibitory effect on the peristaltic actions of the distal intestine. After surgery, the patient's constipation resolved rapidly, suggesting a correlation between PYY producing ovarian carcinoid tumor and constipation. This is the first case report of PYY producing primary strumal carcinoid tumor of the ovary associated with persistent, severe constipation from Korea.

Lymphoepithelioma-like carcinoma of the uterine cervix.

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is exceedingly uncommon. We herein report a rare case of cervical LELC. A 45-year-old woman was admitted to gynecology department with vaginal bleeding for one month. Liquid-based cytology revealed atypical endometrial cells, not otherwise specified on her cervix. On a hysteroscopy, an endocervical mass was identified and the pathologic result was consistent with poorly differentiated squamous cell carcinoma. Magnetic resonance imaging and positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography revealed a 3.1-cm endocervical mass without distant metastasis or enlarged lymph nodes. The International Federation of Gynecology and Obstetrics stage was IB1. A radical hysterectomy and bilateral pelvic lymph node dissection were performed. The pathologic diagnosis was a poorly differentiated carcinoma, showing features of LELC. She has been followed for 8 months without adjuvant treatment since the surgery, during which time there has been no evidence of tumor recurrence or metastasis.

Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling pathway.

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.