Search

Background. Ovarian cancer (OC) is the leading cause of gynecologic malignant tumors. The role of necroptosis-related lncRNAs (NRLs) in OC remains unclear. This study aims to explore the association between NRLs and prognosis in OC patients. Methods. The Cancer Genome Atlas (TCGA) and GTEx datasets were used to obtain OC’s data. A NRLs signature associated with overall survival (OS) was constructed by Cox-LASSO regression analysis in training cohort for calculating risk score and then validated in testing cohort. Subsequently, the area under the curve (AUC) and Kaplan–Meier survival analysis were used to evaluate the predictive accuracy of the risk score. Finally, the immune infiltration and functional enrichment were compared between different risk groups. Results. A 8-NRLs signature including AC245128.3, AL355488.1, AC092794.1, AC068888.2, AL590652.1, AC008982.2, FOXP4-AS1, and Z94721.1 was identified to assess the OS of OC. Kaplan–Meier survival analysis, AUC value, and Cox regression analysis confirmed its predictive value and showed that the clinical outcomes were worse for high-risk patients. There were also differences in immunological functioning and immune pathways between the high-risk and low-risk groups. Conclusions. The signature based on eight NRLs has significant values in predicting prognostic prediction in OC, as well as providing a new sight for targeted therapies.

Aim To introduce the novel use of lauromacrogol for cesarean scar pregnancy (CSP), and to compare the clinical efficacy and safety of curettage combined with ultrasound-guided sclerosant injection (USI) and curettage following uterine artery embolization (UAE) in the treatment of CSP. Methods CSP patients undergoing curettage combined with USI (n = 72) from December 2014 to May 2020 were compared to patient with curettage following UAE (n = 72).The basic clinical findings and clinical outcomes were reviewed between the two groups. Results For USI group, 69 patients underwent successful treatment (95.8% success rate), while the number of cured patients for the UAE group was 70 (97.2% success rate). Differences between USI group and UAE group in intraoperative blood loss (10.0 [10.0-20.0] vs. 10.0 [10.0-20.0] mL) and time for serum β human chorionic gonadotropin (β-hCG) to reduce to normal (28.0 [21.0-40.0] vs. 28.0 [21.0-35.0] days) were not statistically significant. The hospital stay for USI group was significantly shorter than that for UAE group (4.0 [4.0-6.0] vs. 6.0 [5.0-7.0] days, respectively). Statistically significant decreases were noted in hospitalization expenses and adverse events in USI group, compared to UAE group. There was no difference in live birth rate between the two groups with fertility intentions during the follow-up. Conclusion For treatment of CSP, curettage combined with USI yielded clinical results comparable to those of curettage following UAE. Curettage combined with USI was associated with lower hospitalization expenses, shorter hospital stay and less complications, and it merited an effective and safe treatment for CSP.

One type of age-related macular degeneration (AMD), neovascular (nAMD), characterized by choroidal neovascularization (CNV), accounts for the majority of the severe central vision impairment associated with AMD. Endothelial cells (ECs) in direct contact with retinal pigment epithelial (RPE) cells are more prone to the pathological angiogenesis involved in CNV. Herein, we investigated the effect of crosstalk between RPE cells and choroidal endothelial cells (CECs) via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis on the development of choroidal neovascularization (CNV) in vitro and in vivo. ANXA1 expression and secretion from ARPE-19 cells were upregulated by hypoxia. FPR2 expression, especially on the plasma membrane, in HCECs was upregulated under hypoxic conditions. ANXA1 secreted from ARPE-19 cells inhibited NLRP3 inflammasome activation and NLRP3 inflammasome-mediated pyroptosis in HCECs by activating the FPR2/SHP2 axis. Moreover, ANXA1 secreted by ARPE-19 cells promoted behaviors of HCECs, including proliferation, migration, and tube formation, by activating the FPR2/SHP2 axis and inhibiting NLRP3 inflammasome-mediated pyroptosis. Inhibiting the upregulated ANXA1/FPR2/SHP2/NLRP3 inflammasome/pyroptosis axis decreased the volume of CNV. Our data suggest that the crosstalk between RPE cells and CECs via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis promotes CNV. This finding could identify a potential target for the prevention and treatment of CNV.

Objective To introduce an effective approach using the hysteroscopic cold-knife surgery system (HCSS) for suture fixation of the levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with adenomyosis. Design Video description of the surgical procedures to demonstrate the detailed technique. The study was reviewed and approved by the institutional review board of Hangzhou Women’s Hospital. Setting Maternity hospital. Patient(s) A 39-year-old woman diagnosed with adenomyosis had endured 7 years of severe dysmenorrhea and 4 years of heavy menstrual bleeding. She had a past medical history that was significant for expulsion of an LNG-IUD. Transvaginal ultrasonography revealed that her uterus was enlarged by adenomyosis. She insisted on preserving fertility potential. Intervention(s) We proceeded with the HCSS and the uterine cavity was found enlarged significantly. In consideration of the patient’s strong desire for maintaining fertility options, the fixation of the LNG-IUD on the intrauterine posterior wall with an Ethibond suture was performed successfully through an endoscopic needle driver and a knot-pushing device. Proficient endoscopic suturing is the key to the technique. Informed consent was obtained from the patient. Main Outcome Measure(s) Feasibility and value of using the HCSS to fix an LNG-IUD for treatment of adenomyosis. Result(s) The LNG-IUD was fixed successfully by the HCSS with an Ethibond suture on the posterior wall of the uterus within 30 minutes, and the intraoperative blood loss was 2 mL. The patient was discharged 24 hours postoperatively without any adverse perioperative complications. At the one-year follow-up, the patient reported obvious relief of her dysmenorrhea and menorrhagia and no more experience with expulsion. Ultrasound demonstrated normal position of the IUD at 1, 3, 6, and 12 months postoperatively. Conclusion(s) Hysteroscopy presents a clear visual field to locate and fix the IUD. In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of the LNG-IUD using the HCSS can be a minimally invasive and effective alternative for treating adenomyosis, especially in patients who have previously expelled an LNG-IUD, preventing the risk of expulsion.

Wet age‐related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial‐mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti‐vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia‐inducible factor‐1α (HIF‐1α) increases the stability and activation of p53, which activates microRNA‐34a (miRNA‐34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA‐34a that inhibits fibrosis. This study aimed to explore the role of the HIF‐1α/p53/miRNA‐34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia‐induced HIF‐1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE‐19 cells (a human RPE cell line). HIF‐1α‐dependent p53 activation up‐regulated miRNA‐34a expression in ARPE‐19 cells following hypoxia. Moreover, hypoxia‐induced p53‐dependent miRNA‐34a inhibited the expression of Klotho in ARPE‐19 cells. Additionally, the HIF‐1α/p53/miRNA‐34a/Klotho axis facilitated hypoxia‐induced EMT in ARPE‐19 cells. In vivo, blockade of the HIF‐1α/p53/miRNA‐34a/Klotho axis alleviated the formation of mouse laser‐induced CNV and subretinal fibrosis. In short, the HIF‐1α/p53/miRNA‐34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.

To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Moreover, the long-term treatment of vaginal agenesis was followed-up.This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long-term follow-up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS-R).The medians (25th-75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0-59.0) minutes, comparing to 135.0 (117.5-162.5) min for Davydov procedures (p 0.001). The intraoperative blood loss was 20 (7.5-20.0) mL versus 50.0 (50.0-100.0) mL using the modified Vecchietti and Davydov approaches (p 0.001), respectively. In the 39 follow-up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS-R scores between the two groups.Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.

Study Objective To evaluate in vitro fertility (IVF) outcomes of proximal fallopian tube embolization by interventional radiology compared with laparoscopic salpingectomy before embryo transfer (ET) in patients with hydrosalpinx. Design A single-center, off-label, nonrandomized prospective study. Setting Academic university hospital. Patients One hundred and fifty-five patients with hydrosalpinx were identified on ultrasound or hysterosalpingography desiring IVF between April 2016 and December 2017. Interventions Radiologically guided tubal occlusion with embolization microcoils (RTO-EM) and laparoscopic salpingectomy. Measurements and Main Results Of 155 analyzed patients, 42 were treated with RTO-EM and 113 with laparoscopic salpingectomy. The subsequent IVF outcomes including implantation, clinical pregnancy, miscarriage, ectopic pregnancy, and ongoing pregnancy (fetal heartbeat on ultrasound beyond 10 weeks) were compared between the two groups. Implantation and clinical pregnancy per ET cycle in the RTO-EM group were similar to that of the salpingectomy group (26.7% vs. 30.2%, p = .511, and 39.0% vs. 45.3%, p = .400, respectively), with a similar miscarriage rate. There was no statistically significant difference in ectopic pregnancies between the two groups. Moreover, no difference was detected in ongoing pregnancy per cycle between the two groups (33.9% vs. 41.2%, p = .324). The ongoing-pregnancy rate per patient following RTO-EM was 47.6% (20 of 42) compared with 61.9% (70 of 113) following salpingectomy (p = .108; odds ratio: 0.56; 95% confidence interval, 0.27–1.14). Conclusion Pregnancy in the RTO-EM group was comparable to the salpingectomy group in patients with hydrosalpinx prior to ET treatment. Radiologically guided tubal occlusion with embolization microcoils may be an alternative to salpingectomy for patients with hydrosalpinx planning IVF-ET.

Aim To share the experience of local aspiration and instillation of methotrexate (MTX) to selective reduction of live interstitial pregnancy and to evaluate its clinical effect and the outcome of intrauterine pregnancy. Methods Twelve patients with heterotopic interstitial pregnancy were enrolled at Women's Hospital, Zhejiang University School of Medicine, from 2006 to 2017. All the pregnancies were derived from assisted reproductive technology (ART). The transvaginal aspiration to interstitial pregnancy sac and local instillation of MTX (range from 12.5 to 30 mg) were performed for the patients under ultrasound-guide. The prognosis and pregnancy outcomes were followed up. Results No severe side effects of medical treatment were observed in all patients. Three cases underwent subsequent laparotomy cornual resection, and no perioperative complications were found in these three patients. Twelve patients gave birth to 13 healthy infants without congenital anomalies. The average birth weight and gestational age was 2837 g (SD ± 605 g) and 36.8 weeks (SD ± 2.4 weeks). No growth anomalies and mental retardation were observed in live birth offspring. Conclusion The transvaginal ultrasound-guided aspiration and injection of MTX might be a feasible alternative treatment for heterotopic interstitial pregnancy when vital signs of patients are stable.

One type of age-related macular degeneration (AMD), neovascular (nAMD), characterized by choroidal neovascularization (CNV), accounts for the majority of the severe central vision impairment associated with AMD. Endothelial cells (ECs) in direct contact with retinal pigment epithelial (RPE) cells are more prone to the pathological angiogenesis involved in CNV. Herein, we investigated the effect of crosstalk between RPE cells and choroidal endothelial cells (CECs) via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis on the development of choroidal neovascularization (CNV) in vitro and in vivo. ANXA1 expression and secretion from ARPE-19 cells were upregulated by hypoxia. FPR2 expression, especially on the plasma membrane, in HCECs was upregulated under hypoxic conditions. ANXA1 secreted from ARPE-19 cells inhibited NLRP3 inflammasome activation and NLRP3 inflammasome-mediated pyroptosis in HCECs by activating the FPR2/SHP2 axis. Moreover, ANXA1 secreted by ARPE-19 cells promoted behaviors of HCECs, including proliferation, migration and tube formation, by activating the FPR2/SHP2 axis and inhibiting NLRP3 inflammasome-mediated pyroptosis. Inhibiting the upregulated ANXA1/FPR2/SHP2/NLRP3 inflammasome/pyroptosis axis decreased the volume of CNV. Our data suggest that the crosstalk between RPE cells and CECs via the ANXA1/FPR2/NLRP3 inflammasome/pyroptosis axis promotes CNV. This finding could identify a potential target for the prevention and treatment of CNV.

Oxidative stress and inflammation are important pathogenic factors of diabetic retinopathy (DR). DR remains the most common ocular complication caused by diabetes mellitus (DM) and is the leading cause of visual impairment in working-aged people worldwide. Melatonin has attracted extensive attention due to its potent antioxidant and anti-inflammatory effects. In the present study, melatonin inhibited oxidative stress and inflammation by enhancing the expression and activity of silent information regulator factor 2-related enzyme 1 (Sirt1) both in in vitro and in vivo models of DR, and the Sirt1 inhibitor EX-527 counteracted melatonin-mediated antioxidant and anti-inflammatory effects on Müller cells. Moreover, melatonin enhanced Sirt1 activity through the maternally expressed gene 3 (MEG3)/miR-204 axis, leading to the deacetylation of the Sirt1 target genes forkhead box o1 (Foxo1) and nuclear factor kappa B (NF-κB) subunit p65, eventually contribute to the alleviation of oxidative stress and inflammation. The study revealed that melatonin promotes the Sirt1 pathway, thereby protecting the retina from DM-induced damage.

Diabetic retinopathy (DR) is a vision-loss complication caused by diabetes with high prevalence. During DR, the retinal microvascular injury and neurodegeneration derived from chronic hyperglycemia have attracted global attention to retinal Muller cells (RMCs), the major macroglia in the retina contributes to neuroprotection. Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA) dephosphorylates the transcriptional coactivator Yes-associated protein (YAP) to promote the transcription of glutamine synthetase (GS). GS catalyzes the transformation of neurotoxic glutamate (Glu) into nontoxic glutamine (Gln) to activate the mammalian target of rapamycin complex 1 (mTORC1), which promotes the activation of RMCs. In this study, in vitro MIO-M1 cell and in vivo mouse high-fat diet and streptozotocin (STZ)-induced diabetic model to explore the role of the PPP1CA/YAP/GS/Gln/mTORC1 pathway on the activation of MRCs during DR. Results showed that PPP1CA promoted the dephosphorylation and nuclear translocation of YAP in high glucose (HG)-exposed MIO-M1 cells. YAP transcribed GS in HG-exposed MIO-M1 cells in a TEAD1-dependent and PPP1CA-dependent way. GS promoted the biosynthesis of Gln in HG-exposed MIO-M1 cells. Gln activated mTORC1 instead of mTORC2 in HG-exposed MIO-M1 cells. The proliferation and activation of HG-exposed MIO-M1 cells were PPP1CA/YAP/GS/Gln/mTORC1-dependent. Finally, RMC proliferation and activation during DR were inhibited by the PPP1CA/YAP/GS/Gln/mTORC1 blockade. The findings supplied a potential idea to protect RMCs and alleviate the development of DR.

Neovascular age‐related macular degeneration (AMD), which is characterized by choroidal neovascularization (CNV), leads to vision loss. M2 macrophages produce vascular endothelial growth factor (VEGF), which aggravates CNV formation. The histone acetyltransferase p300 enhances the stability of spliced X‐box binding protein 1 (XBP1s) and promotes the transcriptional activity of the XBP1s target gene homocysteine inducible endoplasmic reticulum protein with ubiquitin‐like domain 1 (Herpud1). Herpud1 promotes the M2 polarization of macrophages. This study aimed to explore the roles of the p300/XBP1s/Herpud1 axis in the polarization of macrophages and the pathogenesis of CNV. Hypoxia‐induced p300 interacted with XBP1s to acetylate XBP1s in RAW264.7 cells. Additionally, hypoxia‐induced p300 enhanced the XBP‐1s‐mediated unfolded protein response (UPR), alleviated the proteasome‐dependent degradation of XBP1s and enhanced the transcriptional activity of XBP1s for Herpud1. The hypoxia‐induced p300/XBP1s/Herpud1 axis facilitated RAW264.7 cell M2 polarization. Knockdown of the p300/XBP1s/Herpud1 axis in RAW264.7 cells inhibited the proliferation, migration and tube formation of mouse choroidal endothelial cells (MCECs). The p300/XBP1s/Herpud1 axis increased in infiltrating M2‐type macrophages in mouse laser‐induced CNV lesions. Blockade of the p300/XBP1s/Herpud1 axis inhibited macrophage M2 polarization and alleviated CNV lesions. Our study demonstrated that the p300/XBP1s/Herpud1 axis in infiltrating macrophages increased the M2 polarization of macrophages and the development of CNV.

Purpose This study examined the role of the CSF1/CSF1Raxis in the crosstalk between choroidal vascular endothelial cells (CVECs) and macrophages during the formation of choroidal neovascularization (CNV). Methods Quantitative reverse transcriptase (QRT)-PCR, Western blot and ELISA measured the production and release of CSF1 from human choroidal vascular endothelial cells (HCVECs) under hypoxic conditions. Western blot detected CSF1 released from HCVECs under hypoxic conditions that activated the PI3K/AKT/FOXO1 axis in human macrophages via binding to CSF1R. Transwell migration assay, qRT-PCR, and Western blot detected the effect of CSF1 released from HCVECs on macrophage migration and M2 polarization via the CSF1R/PI3K/AKT/FOXO1 pathway. Incorporation of 5-ethynyl-20-deoxyuridine, transwell migration, and tube formation assays detected the effects of CSF1/CSF1R on the behaviors of HCVECs. Fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and immunofluorescence detected the effect of blockade of CSF1/CSF1R on mouse laser-induced CNV. Color fundus photograph, ICGA, and FFA detected CNV lesions in neovascular AMD (nAMD) patients. ELISA detected CSF1 and CSF1R in the aqueous humor of age-related cataract and nAMD patients. Results CSF1 released from HCVECs under hypoxic conditions activated the PI3K/AKT/FOXO1 axis in human macrophages via binding to CSF1R, promoting macrophage migration and M2 polarization via up-regulation of the CSF1R/PI3K/AKT/FOXO1 pathway. Human macrophages promoted the proliferation, migration, and tube formation of HCVECs in a CSF1/CSFR1-dependent manner under hypoxic conditions. CSF1/CSF1R blockade ameliorated the formation of mouse laser-induced CNV. CSF1 and CSF1R were increased in the aqueous humor of nAMD patients. Conclusions Our results affirmed the crucial role of CSF1/CSF1R in boosting the formation of CNV and offered potential molecular targets for the treatment of nAMD.

Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Muller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response.

Primary ovarian insufficiency (POI) leads to infertility and premature menopause in young women. The genetic etiology of this disorder remains unknown in most patients. Using whole exome sequencing of a large Chinese POI pedigree, we identified a heterozygous 5 bp deletion inducing a frameshift in BNC1, which is predicted to result in a non-sense-mediated decay or a truncated BNC1 protein. Sanger sequencing identified another BNC1 missense mutation in 4 of 82 idiopathic patients with POI, and the mutation was absent in 332 healthy controls. Transfection of recombinant plasmids with the frameshift mutant and separately with the missense mutant in HEK293T cells led to abnormal nuclear localization. Knockdown of BNC1 was found to reduce BMP15 and p-AKT levels and to inhibit meiosis in oocytes. A female mouse model of the human Bnc1 frameshift mutation exhibited infertility, significantly increased serum follicle-stimulating hormone, decreased ovary size and reduced follicle numbers, consistent with POI. We report haploinsufficiency of BNC1 as an etiology of human autosomal dominant POI.

Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.

Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease.

Neovascular age-related macular degeneration (nAMD), featured as choroidal neovascularization (CNV), can cause blindness in the elderly population. MLN4924, a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally down-regulated protein 8)-activating enzyme (NAE), inhibits the proliferation, angiogenesis and inflammation of multiple cancers via up-regulating hedgehog pathway-regulated autophagy. MLN4924 intraperitoneal injection mitigated the leakage, area and volume of mouse laser-induced CNV lesion. Additionally, compared to CNV 7 d group, MLN4924 treated mouse retina-retinal pigment epithelium (RPE)-choroid complex showed decreased expression of hedgehog pathway-associated molecules patched 1 (PTCH1), smoothened (SMO), GLI family zinc finger 1 (GLI1) and GLI family zinc finger 2 (GLI2) with increased expression of autophagy-associated molecules sequestosome 1 (p62) and LC microtubule-associated protein 1 light chain 3 (LC3). Meanwhile, human choroidal endothelial cells (HCECs) exposed to hypoxia condition also showed decreased expression of hedgehog pathway-associated molecules and increased expression of autophagy-associated molecules. Compared to hypoxia + MLN4924 group, SMO agonist SAG up-regulated hedgehog pathway and down-regulated autophagy, whereas autophagy inhibitor PIK-III inhibited autophagy with no effect on hedgehog pathway, indicating that MLN4924 facilitated autophagy of HCECs via hindering hedgehog pathway under hypoxia condition. Finally, MLN4924 inhibited proliferation, migration and tube formation of HCECs via boosting hedgehog pathway-regulated autophagy. In summary, MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. The results provide a potential interfering strategy for nAMD targeting the autophagy of choroidal endothelial cells.

Aims: Early evaluation of pelvic floor muscle (PFM) in postpartum women is important for the treatment of stress urinary incontinence (SUI). Digital vaginal palpation and electromyography (EMG) evaluation based on Glazer protocol are widely used for the assessment of PFM. However, the correlation among digital palpation, EMG, and morbidity of postpartum SUI is still unclear. This study aims to investigate the relationship between postpartum SUI and PFM examinations. Methods: This hospital-based cross-sectional study included 1,380 parturients during September 2016 to January 2018. We collected the clinical characteristics, PFM strength, and EMG variables of parturients 6–8 weeks after birth. Then the correlation among the results of EMG, digital palpation, and the occurrence of SUI was analyzed. Results: There is no significant difference in digital palpation scores of PFM strength between SUI and non-SUI parturients. The EMG values were closely related to SUI: the multivariate logistic regression revealed that the most reliable evaluation indicators of postpartum SUI were pelvic floor contractile amplitude of endurance contraction (B = 0.021, p = 0.019) and pretest resting baseline (B = 0.056, p = 0.019). Correlation analysis demonstrated that the contraction variables of EMG had a significant correlation with the digital palpation PFM strength in postpartum women (r = 0.467–0.545, p < 0.001). Conclusion: The EMG proved to be reliable in assessing the PFM function in postpartum women. The decreased PFM activity, according to EMG, was correlated with postpartum SUI. Although digital palpation scores were positively correlated with EMG results, no correlation was observed with SUI incidence.

The changes of sialic acid (SA) expression on cell surface are closely associated with various malignant diseases. The analysis of SA expression is therefore becoming an important parameter in clinical diagnosis. In this paper, we reported a sensitive electrochemical cytosensor for the analysis of SA expression on cell surface using three-dimensional architecture of Au@BSA and nanoprobes of carbon nanospheres modified with Au nanoparticles (CNS/AuNPs). Au@BSA microspheres provided an effective matrix for binding of Concanavalin A (Con A) which acted as the recognizer and capturer for cells via the specific affinity to mannose and the core trimannoside of N-glycan on the cell surface. On the basis of the specific recognition of Sambucus nigra agglutinin (SNA) to cell surface sialic acid groups, the SNA and HRP modified CNS/AuNPs nanoprobes were introduced onto the electrode surface, and amplified signals were produced by an enzymatic catalytic reaction of HRP toward the oxidation of hydroquinone (HQ) by H2O2. This cytosensor was successfully applied to the analysis of SA expression on cell surface disturbed by sialidase and to detect MCF-7 cells and BGC-823 cells with a low detection limit of 40 cells mL−1 and 120 cells mL−1. Therefore, the proposed strategy offers a new way for insight into the SA function in biological processes and helps improve cancer diagnosis and treatment.

Based on melamine binding-triggered triplex formation and subsequent activation of Mg(2+)-dependent DNAzymes, a novel strategy for DNAzyme regulation was proposed and developed for melamine recognition.

It is widely acknowledged that sialic acid (SA) overexpression on cell surfaces has been thought to be a characteristic feature associated with many malignant diseases. In this paper, we report a new strategy for SA expression evaluation and electrochemical cytosensing of living cells. High selectivity and sensitivity were achieved by combining 3-aminophenylboronic acid (APBA) modified carbon nanospheres (CNS-APBA) for SA recognition and horseradish peroxidases (HRP) decorated on gold nanoparticles (Au-HRP NPs) for signal amplification. The HRP labels can effectively catalyze the oxidation of aniline in the presence of H2O2 to form polyaniline (PAn). The relatively positive detection potential range for PAn completely excluded the conventional interference from dissolved oxygen. Based on the dual signal amplification by functionalized carbon nanospheres and enzymatically produced polyaniline, the designed cytosensor can be used for SA evaluation on cancer cell surfaces and highly sensitive cell detection with a wide calibration range (from 5.0 × 102 to 1.0 × 106 cells per mL for MCF-7 cells and from 1.0 × 103 to 1.0 × 106 cells per mL for BGC-823 cells) and a low detection limit (25 cells per mL for MCF-7 cells and 800 cells per mL for BGC-823 cells). This strategy provides a valuable tool for the evaluation of sialic acid on cancer cells and great potency for cancer study.

In this paper, a reaction-diffusion equation with discrete time delay that describes the dynamics of the blood cell production is analyzed. The existence of the traveling wave front solutions is demonstrated using the technique of upper and lower solutions and the associated monotone iteration.

This study was carried out to explore associations between assisted reproductive technology (ART) and maternal and neonatal outcomes compared with similar outcomes following spontaneously conceived births. We conducted a retrospective cohort study of pregnancies conceived by ART (N = 2641) during 2006–2014 compared to naturally conceived pregnancies (N = 5282) after matching for maternal age and birth year. Pregnancy complications, perinatal complications and neonatal outcomes of enrolled subjects were investigated and analysed by multivariate logistic regression. We found that pregnancies conceived by in vitro fertilization (IVF) were associated with a significantly increased incidence of gestational diabetes mellitus, gestational hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of membranes, placental adherence, postpartum haemorrhage, polyhydramnios, preterm labour, low birth weight, and small-for-date infant compared with spontaneously conceived births. Pregnancies conceived by intracytoplasmic sperm injection (ICSI) showed similar elevated complications, except some of the difference narrowed or disappeared. Singleton pregnancies or nulliparous pregnancies following ART still exhibited increased maternal and neonatal complications. Therefore, we conclude that pregnancies conceived following ART are at increased risks of antenatal complications, perinatal complications and poor neonatal outcomes, which may result from not only a higher incidence of multiple pregnancy, but also the manipulation involved in ART processes.

A melamine aptamer derived from an abasic-site-containing triplex molecular beacon (tMB) was designed and developed for sensitive recognition of melamine by integrating tMBs and fluorescent silver nanoclusters (Ag NCs).

In this paper, a two-species cooperating model with free diffusion and self-diffusion is investigated. The existence of the global solution is first proved by using lower and upper solution method. Then the sufficient conditions are given for the solution to blow up in a finite time. Our results show that the solution is global if the intra-specific competition is strong, while if the intra-specific competition is weak and the self-diffusion rate is small, blow-up occurs provided that the initial value is large enough or the free diffusion rate is small. Numerical simulations are also given to illustrate the blow-up results. MSC:35K57, 92D25.

This paper proposed an improved face recognition method based on Gabor wavelet transform and SVM. Firstly, the approach utilizes discrete Gabor wavelet transform to face images. then the dimensions of Gabor feature vectors are reduced and transform feature base can be got by using the improved Fisher face method proposed in this paper. by projecting the face image onto the base, the transform coefficient used to be the input of classifier can be got. Finally face image can be classified using a SVM with error correction. Experiment results show that the method of this paper is robust and effective.