Search

Endocytosis represents a category of regulated active transport mechanisms. These encompass clathrin-dependent and -independent mechanisms, as well as fluid phase micropinocytosis and macropinocytosis, each demonstrating varying degrees of specificity and capacity. Collectively, these mechanisms facilitate the internalization of cargo into cellular vesicles. Pregnancy is one such physiological state during which endocytosis may play critical roles. A successful pregnancy necessitates ongoing communication between maternal and fetal cells at the maternal-fetal interface to ensure immunologic tolerance for the semi-allogenic fetus whilst providing adequate protection against infection from pathogens, such as viruses and bacteria. It also requires transport of nutrients across the maternal-fetal interface, but restriction of potentially harmful chemicals and drugs to allow fetal development. In this context, trogocytosis, a specific form of endocytosis, plays a crucial role in immunological tolerance and infection prevention. Endocytosis is also thought to play a significant role in nutrient and toxin handling at the maternal-fetal interface, though its mechanisms remain less understood. A comprehensive understanding of endocytosis and its mechanisms not only enhances our knowledge of maternal-fetal interactions but is also essential for identifying the pathogenesis of pregnancy pathologies and providing new avenues for therapeutic intervention.

Abstract Background Studies on the choroid of myopic eyes with posterior staphyloma have shown that choroidal thickness decreased. This retrospective study further analysed the effects of posterior scleral staphyloma on choroidal blood vessels and matrix components compared to non-pathological myopia. Methods In this cross-sectional study, ninety-one eyes were divided into pathological (posterior staphyloma) and non-pathological myopia. The latter was further divided into three groups (Group 1: 26 mm ≤ axial length; Group 2: 24 mm ≤ axial length 26 mm.

PurposeWe aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS).MethodsA total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters.ResultsThe angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators.ConclusionsThe OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions.Trial registrationChiCTR2100050428.

Abstract Background Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score. Methods This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations. Results The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P

Ischemic accumulation of succinate causes cerebral damage by excess production of reactive oxygen species. However, it is unknown whether ischemic accumulation of succinate affects neural stem cell proliferation. In this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery. We found that succinate levels increased in serum and brain tissue (cortex and hippocampus) after ischemia/reperfusion injury. Oxygen-glucose deprivation and reoxygenation stimulated primary neural stem cells to produce abundant succinate. Succinate can be converted into diethyl succinate in cells. Exogenous diethyl succinate inhibited the proliferation of mouse-derived C17.2 neural stem cells and increased the infarct volume in the rat model of cerebral ischemia/reperfusion injury. Exogenous diethyl succinate also increased the succinylation of the Rho family GTPase Cdc42 but repressed Cdc42 GTPase activity in C17.2 cells. Increasing Cdc42 succinylation by knockdown of the desuccinylase Sirt5 also inhibited Cdc42 GTPase activity in C17.2 cells. Our findings suggest that ischemic accumulation of succinate decreases Cdc42 GTPase activity by induction of Cdc42 succinylation, which inhibits the proliferation of neural stem cells and aggravates cerebral ischemia/reperfusion injury.

AIM: To explore the difference of tear film stability among different lipid layer thickness.METHOD: A total of 194 dry eye patients(384 eyes)admitted to our hospital from June 2020 to December 2021 were enrolled in this study. The tear meniscus height, the first tear film break-up time and lipid layer thickness were measured by corneal topographer. The tear meniscus height and the first tear film break-up time among different lipid layer thickness were compared and the correlation between them was analyzed.RESULTS: The included patients(384 eyes)were divided into lipid rich group(49 eyes), lipid balance group(27 eyes), slight lipid deficiency group(266 eyes)and significant lipid deficiency group(42 eyes)according to the lipid layer thickness. The differences of the tear meniscus height were statistically different(P=0.022), while the differences of the first tear film break-up time were not statistically different(P=0.322). The lipid layer thickness was positively correlated with tear meniscus height(rs=0.143, P=0.006). There was no correlation between lipid layer thickness and the first tear film break-up time(rs=-0.090, P=0.083), nor was there correlation between tear meniscus height and the first tear film break-up time(rs=0.038, P=0.460).CONCLUSION: There was no significant difference in tear film stability in dry eye patients with different lipid layer thickness.

Abstract Background Ocular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS). Methods In total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA. Results In this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P

Abstract Background The laboratory mouse was domesticated from the wild house mouse. Understanding the genetics underlying domestication in laboratory mice, especially in the widely used classical inbred mice, is vital for studies using mouse models. However, the genetic mechanism of laboratory mouse domestication remains unknown due to lack of adequate genomic sequences of wild mice. Results We analyze the genetic relationships by whole-genome resequencing of 36 wild mice and 36 inbred strains. All classical inbred mice cluster together distinctly from wild and wild-derived inbred mice. Using nucleotide diversity analysis, Fst, and XP-CLR, we identify 339 positively selected genes that are closely associated with nervous system function. Approximately one third of these positively selected genes are highly expressed in brain tissues, and genetic mouse models of 125 genes in the positively selected genes exhibit abnormal behavioral or nervous system phenotypes. These positively selected genes show a higher ratio of differential expression between wild and classical inbred mice compared with all genes, especially in the hippocampus and frontal lobe. Using a mutant mouse model, we find that the SNP rs27900929 (T>C) in gene Astn2 significantly reduces the tameness of mice and modifies the ratio of the two Astn2 (a/b) isoforms. Conclusion Our study indicates that classical inbred mice experienced high selection pressure during domestication under laboratory conditions. The analysis shows the positively selected genes are closely associated with behavior and the nervous system in mice. Tameness may be related to the Astn2 mutation and regulated by the ratio of the two Astn2 (a/b) isoforms.

Abstract Background To investigate the structural and functional changes of the retina in patients with different degrees of internal carotid artery (ICA) stenosis. Methods This cross-sectional study included patients with varying degrees ICA stenosis. Clinical characteristics of 41 patients were collected after being divided into four groups according to the ICA stenosis indicated by computed tomographic angiography (Group 0: without ICA stenosis, Group 1: ipsilateral slight ICA stenosis, Group 2: ipsilateral moderate ICA stenosis, Group 3: ipsilateral severe ICA stenosis). Retinal vessel caliber (RVC) was measured quantitatively with the Integrative Vessel Analysis software. The retinal sensitivity was examined with the MP-3 microperimeter. The relationships among central retinal artery equivalent (CRAE), central retinal vein equivalent, arteriole to venule ratio (AVR), mean retinal sensitivity (MS) and ICA stenosis degree were analysed. Results The CRAE in Group 3 were significantly smaller compared with Group 0, Group 1 and Group 2 (P

Abstract Background Preeclampsia (PE), a placenta-associated pregnancy complication, is the leading cause of maternal and perinatal morbidity and mortality. Met/Erk signaling is inhibited in the placentas of patients with early-onset preeclampsia (E-PE), but the underlying mechanisms remain elusive. In this study, the expression modes of Met and endocytic vesicles in normal and preeclamptic placentas were compared. Biotinylation internalization/recycling assays were used to measure the endocytosis of Met under hypoxia and normoxia in HTR8/SVneo cells. In addition, the expression level of Cbl, a specific E3 ligase of Met, was measured under hypoxia and normoxia, and the endocytosis of Met was studied by using confocal microscopy. Results We found considerable intracellular accumulation of Met, which was colocalized with caveolin-1 (CAV-1), in trophoblasts from E-PE placentas. Prolonged hypoxic stimulation led to the remarkable augmentation of CAV-1-mediated Met endocytosis in HTR8/SVneo cells. In addition, the expression of Cbl was substantially repressed by sustained hypoxia, disrupting ubiquitin degradation and the subsequent intracellular accumulation of Met in HTR8/SVneo cells. The abnormal degradation of Met hampered the ability of hepatocyte growth factor (HGF) to promote trophoblast cell invasion. In E-PE placentas, aberrant upregulation of CAV-1 and downregulation of Cbl were observed in parallel to the intracellular accumulation of Met. Conclusions These findings reveal that prolonged hypoxic stress induces the augmentation of endocytosis and repression of ubiquitin-mediated Met degradation, which leads to the impaired regulation of trophoblast invasion by HGF/Met signaling. These data provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype.

Abstract. Serving as the interface between the fetal and maternal environments during gestation, the placenta plays critical roles in the protection of the developing fetus and the maintenance of maternal health. The placenta is primarily derived from the embryonic trophectoderm which differentiates into various subtypes of trophoblast cells through villous and extravillous pathways. The interactions among trophoblasts and multiple decidual cells and immune cells at the maternal-fetal interface fundamentally form the functional units of the placenta, which are responsible for blood perfusion and maternal-fetal material exchange, immune tolerance, and the regulation of pregnancy adaptation. Defects in placental development and functional maintenance are in tight association with adverse pregnancy outcomes such as preeclampsia. In this article, we review recent advances on human trophoblast cell differentiation and the construction of placental functional units and discuss the placental and maternal factors that may contribute to the occurrence of preeclampsia.

An orthogonal set of states in multipartite systems is called to be strong quantum nonlocality if it is locally irreducible under every bipartition of the subsystems \cite{Halder19}. In this work, we study a subclass of locally irreducible sets: the only possible orthogonality preserving measurement on each subsystems are trivial measurements. We call the set with this property is locally stable. We find that in the case of two qubits systems locally stable sets are coincide with locally indistinguishable sets. Then we present a characterization of locally stable sets via the dimensions of some states depended spaces. Moreover, we construct two orthogonal sets in general multipartite quantum systems which are locally stable under every bipartition of the subsystems. As a consequence, we obtain a lower bound and an upper bound on the size of the smallest set which is locally stable for each bipartition of the subsystems. Our results provide a complete answer to an open question (that is, can we show strong quantum nonlocality in $\mathbb{C}^{d_1} \otimes \mathbb{C}^{d_1}\otimes \cdots \otimes \mathbb{C}^{d_N} $ for any $d_i \geq 2$ and $1\leq i\leq N$?) raised in a recent paper \cite{Shi22N}. Compared with all previous relevant proofs, our proof here is quite concise.

AIM: To observe the location characteristics of the earliest tear film breakup in elderly patients with dry eyes.METHODS: Cross-sectional study. The 154 elderly patients with dry eyes in our hospital from July 2019 to December 2019 were included, with 143 right eyes, 124 left eyes, and 71 patients were males, 83 patients were females, aged 68-90(mean: 73.40±4.13)years old. The location of the earliest tear film breakup was investigated by using corneal topographer. The cornea was separated to four sectors to record the earliest tear film breakup location by anticlockwise order. The sector corresponding to the right eye was nasal superior, temporal superior, temporal inferior and nasal inferior respectively. And it corresponding to the left eye was temporal superior, nasal superior, nasal inferior and temporal inferior respectively. Then the sector which was the earliest tear film breakup location was recorded. At the same time, the distance which was from the earliest tear film breakup location to the centre of cornea was recorded too.RESULTS: The highest constituent ratio of area of right eye was nasal inferior(28.7%), then was temporal inferior(27.3%), nasal superior(20.3%), temporal superior(11.2%), and the constituent ratio of earliest tear film breakup occurred in 2-3 areas at the same time was 12.6%. The constituent ratio of the earliest tear film breakup area of left eye also was nasal inferior(31.5%), then was temporal inferior(25.0%), nasal superior(23.4%), temporal superior(11.3%), the constituent ratio of earliest tear film breakup occurred in 2-3 areas at the same time was 8.9%. There was no difference in the constituent ratio of tear film breakup area between two eyes(χ2=1.443, P=0.837). The distance from the earliest tear film breakup area of the nasal inferior quadrant to the centre of cornea was mostly the zone from 1.5-2mm and 2-2.5mm in both eyes.CONCLUSION: There is a certain regularity in the characteristics of tear film breakup area in elderly patients with dry eyes, and the earliest tear film breakup area of both eyes is mainly occurred in nasal inferior, and there is no significant difference between two eyes.

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8+ effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

Plant exosome-like nanoparticles (ELNs) have shown great potential in treating tumor and inflammatory diseases, but the neuroprotective effect of plant ELNs remains unknown. In the present study, we isolated and characterized novel ELNs from Momordica charantia (MC) and investigated their neuroprotective effects against cerebral ischemia-reperfusion injury. In the present study, MC-ELNs were isolated by ultracentrifugation and characterized. Male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and MC-ELN injection intravenously. The integrity of the blood–brain barrier (BBB) was examined by Evans blue staining and with the expression of matrix metalloproteinase 9 (MMP-9), claudin-5, and ZO-1. Neuronal apoptosis was evaluated by TUNEL and the expression of apoptotic proteins including Bcl2, Bax, and cleaved caspase 3. The major discoveries include: 1) Dil-labeled MC-ELNs were identified in the infarct area; 2) MC-ELN treatment significantly ameliorated BBB disruption, decreased infarct sizes, and reduced neurological deficit scores; 3) MC-ELN treatment obviously downregulated the expression of MMP-9 and upregulated the expression of ZO-1 and claudin-5. Small RNA-sequencing revealed that MC-ELN-derived miRNA5266 reduced MMP-9 expression. Furthermore, MC-ELN treatment significantly upregulated the AKT/GSK3β signaling pathway and attenuated neuronal apoptosis in HT22 cells. Taken together, these findings indicate that MC-ELNs attenuate ischemia-reperfusion–induced damage to the BBB and inhibit neuronal apoptosis probably via the upregulation of the AKT/GSK3β signaling pathway.

Unextendible product basis (UPB), a set of incomplete orthonormal product states whose complementary space has no product state, is very useful for constructing bound entangled states. Naturally, instead of considering the set of product states, Bravyi and Smolin considered the set of maximally entangled states. They introduced the concept of unextendible maximally entangled basis (UMEB), a set of incomplete orthonormal maximally entangled states whose complementary space contains no maximally entangled state [Phys. Rev. A 84, 042,306 (2011)]. An entangled state whose nonzero Schmidt coefficients are all equal to 1/k is called a special entangled state of “type k”. In this paper, we introduce a concept named special unextendible entangled basis of “type k” which generalizes both UPB and UMEB. A special unextendible entangled basis of “type k” (SUEBk) is a set of incomplete orthonormal special entangled states of “type k” whose complementary space has no special entangled state of “type k”. We present an efficient method to construct sets of SUEBk. The main strategy here is to decompose the whole space into two subspaces such that the rank of each element in one subspace can be easily upper bounded by k while the other one can be generated by two kinds of the special entangled states of “type k”. This method is very effective when k = pm ≥ 3 where p is a prime number. For these cases, we can obtain sets of SUEBk with continuous integer cardinality when the local dimensions are large.

Depletion of hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor (c-Met) in mice leads to fetal lethality and placental maldevelopment. However, the dynamic change pattern of HGF/c-Met signaling during placental development and its involvement in the early differentiation of trophoblasts remain to be elucidated. In this study, using in situ hybridization assay, we elaborately demonstrated the spatial-temporal expression of Hgf and c-Met in mouse placenta from E5.5, the very early stage after embryonic implantation, to E12.5, when the placental structure is well developed. The concentration of the soluble form of c-Met (sMet) in maternal circulation peaked at E10.5. By utilizing the induced differentiation model of mouse trophoblast stem cells (mTSCs), we found that HGF significantly promoted mTSC differentiation into syncytiotrophoblasts (STBs) and invasive parietal trophoblast giant cells (PTGCs). Interestingly, sMet efficiently reversed the effect of HGF on mTSC differentiation. These findings indicate that HGF/c-Met signaling participates in regulating placental trophoblast cell fate at the early differentiation stage and that sMet acts as an endogenous antagonist in this aspect.

The study investigated the regulation of Smad2 by miR-18a and its role in preeclampsia (PE). Bioinformatics analysis showed that both Smad2 and Smad3 were the predicted targets for miR-18a. Mass spectrum analysis showed that two mature Smad2 isoforms existed in human placenta: full length, Smad2(FL), and that lacking exon3, Smad2(Δexon3). The protein level of Smad2(FL), but not Smad2(Δexon3) or Smad3, was significantly increased in severe PE (sPE) placenta, which was inversely correlated with the level of miR-18a. Elevated Smad2(FL) phosphorylation level appeared in sPE placenta, and Smad2 was colocalized with miR-18a in various subtypes of trophoblasts in human placenta. Smad2(FL) was validated as the direct target of miR-18a in HTR8/SVneo cells. miR-18a enhanced trophoblast cell invasion, which was blocked by the overexpression of Smad2(FL). Furthermore, overexpression of miR-18a repressed Smad2 activation and the inhibition of trophoblast cell invasion by transforming growth factor-β (TGF-β). In conclusion, our results suggest that miR-18a inhibits the expression of Smad2(FL), but not Smad2(Δexon3) or Smad3, which can reduce TGF-β signaling, leading to the enhancement of trophoblast cell invasion. A lack of miR-18a, which results in the upregulation of Smad2(FL), contributes to the development of PE.

AIM: To evaluate whether narrowing of internal carotid artery siphon (ICAS) may increase the risk of developing non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: Totally 30 consecutive patients who had unilateral NAION and 30 gender-matched control subjects were recruited in the present study. The diameter of ICAS of all the participants were measured using head-and-neck computed tomographic angiography (CTA). Color doppler flow imaging (CDI) was used to measure the haemodynamics parameters of ICAS and short posterior ciliary arteries (SPCAs) in all subjects. Comparison of parameters between the NAION patients and controls as well as between the two sides within the patients were performed. The correlation between the diameter of ICAS and NAION was analyzed. RESULTS: A comparison of parameters between the affected side of the NAION patients and the controls, including the diameter of ICAS, the resistance index (RI) of ICAS, the blood flow velocities of SPCAs and RI of SPCAs, showed significantly difference (P

Blood–brain barrier (BBB) dysfunction causing edema and hemorrhagic transformation is one of the pathophysiological characteristics of stroke. Protection of BBB integrity has shown great potential in improving stroke outcome. Here, we assessed the efficacy of exosomes extracted from healthy rat serum in protection against ischemic stroke in vivo and in vitro. Exosomes were isolated by gradient centrifugation and ultracentrifugation and exosomes were characterized by transmission electron microscopy (TEM) and nanoparticle tracking video microscope. Exosomes were applied to middle cerebral artery occlusion (MCAO) rats or brain microvascular endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD) injury. Serum-derived exosomes were injected intravenously into adult male rats 2 h after transient MCAO. Infarct volume and gross cognitive function were assessed 24 h after reperfusion. Poststroke rats treated with serum-derived exosomes exhibited significantly reduced infarct volumes and enhanced neurological function. Apoptosis was assessed via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and the expression of B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3 24 h after injury. Our data showed that serum exosomes treatment strikingly decreased TUNEL+ cells in the striatum, enhanced the ratio of Bcl-2 to Bax, and inhibited cleaved caspase-3 production in MCAO rats and OGD/reoxygenation insulted bEnd.3 cells. Under the consistent treatment, the expression of microtubule-associated protein 1 light chain 3B-II (LC3B-II), LC3B-I, and Sequestosome-1 (SQSTM1)/p62 was detected by Western blotting. Autolysosomes were observed via TEM. We found that serum exosomes reversed the ratio of LC3B-II to LC3B-I, prevented SQSTM1/p62 degradation, autolysosome formation, and autophagic flux. Together, these results indicated that exosomes isolated from healthy serum provided neuroprotection against experimental stroke partially via inhibition of endothelial cell apoptosis and autophagy-mediated BBB breakdown. Intravenous serum-derived exosome treatment may, therefore, provide a novel clinical therapeutic strategy for ischemic stroke.

AIM: To investigate the affecting factors of parapapillary gamma and delta zones and other fundus morphological features in high myopia. METHODS: Seventy high myopia patients were included in this retrospective observational study and 47 patients were female. Patients were divided into three groups: no posterior staphyloma (no PS), PS with myopic traction maculopathy (PS with MTM), and PS without MTM using 3-dimensional magnetic resonance imaging and optical coherence tomography. MTM patients were further classified into three types [epiretinal membrane, macular hole, and macular retinoschisis (MRS)]. Diameters of the gamma and delta zones were measured among other morphometric variables using fundus photographs. RESULTS: Of the 70 individuals (127 eyes), the mean age was 57.46±13.56y. In univariate analysis, morphological features changed most dramatically in PS with MTM patients, who had the largest gamma zone diameters, the largest disk-fovea distance (DFD) and disk-fovea angle, and the smallest angle kappa and vertical distance of temporal arterial arcade. However, their horizontal delta zone diameter was smaller than in the patients with PS yet without MTM. In multivariate analysis, with axial length (AL) and age adjusted, the horizontal diameter in the delta zone of the PS without MTM group was still significantly larger than in the PS with MTM group (P=0.024). Comparing the three subtypes of MTM patients, the diameters of the gamma zone and DFD in MRS group were the largest. CONCLUSION: The characteristics of the gamma and delta zones change inconsistently in different stages of high myopia. These changes may be associated with anatomical changes caused by local traction. Factors such as PS, AL and age play an important role. These findings may provide a hint about the pathogenesis of traction in high myopia.

Abstract Background Endoscopic biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is the most common form of palliation for malignant hilar obstruction. However, ERCP in such cases is associated with a risk of cholangitis. The incidence of post-ERCP cholangitis is particularly high in Bismuth type IV hilar obstruction, and this risk is further increased when the contrast injected for cholangiography is not drained. The present study aims to compare the incidence of cholangitis associated with the use of a contrast agent, air and CO2 for cholangiography in type IV hilar biliary lesions. Methods The clinical data of consecutive 70 patients with type IV hilar obstruction, who underwent ERCP from October 2013 to November 2017, were retrospectively analyzed. These patients were divided into three groups based on the agent used for cholangiography: group A, contrast (n = 22); group B, air (n = 18); group C, CO2 (n = 30). These three methods of cholangiography were chronologically separated. Prior to the ERCP, MRCP was obtained from all patients to guide the endoscopic intervention. Results At baseline, there was no significant difference in terms of the patient’s age, gender, symptoms and liver function tests among the three groups (P > 0.05). The complication rates were significantly higher in group A than in groups B and C (63.6% vs. 26.7 and 27.8%, P 0.05). Furthermore, there was no significant difference between groups B and C in terms of primary end points. Conclusion CO2 or air cholangiography during ERCP for type IV hilar obstruction is associated with reduced risk of post-ERCP cholangitis, when compared to conventional contrast agents.

Tomato (Solanum lycopersicum) stress resistance and fruit total soluble solid (TSS) content have changed dramatically during selective breeding, and transcriptome variation has played a critical role in this rewiring. However, the single tomato reference genome impedes characterization of whole-transcriptome variation during domestication and breeding at the population level. Here, we constructed a pan-transcriptome of orange-stage tomato fruit, and investigated global expression presence/absence variation (ePAV) and differentially expressed genes (DEGs) based on RNA sequencing (RNA-seq) data from 399 tomato accessions. A total of 7 181 genes absent from the reference genome were identified, 6 122 of which were ePAV genes during tomato domestication and breeding including resistance genes such as late blight resistance gene PIM_DN29746_c0_g3_i1 and peroxidase P7-like gene PIM_DN30274_c0_g2_i1. In addition, 3 629 genes were significantly differentially expressed during tomato selection, among which 19 genes were associated with the reduced fruit TSS content of modern tomato cultivars, including LIN5, TIV1, and seven novel sugar transporter genes. Our results indicate that natural and artificial selection greatly shaped the tomato transcriptome, thereby altering the fruit TSS content and resistance to abiotic and biotic stresses.

AIM: To evaluate the effect of internal limiting membrane (ILM) peeling with indocyanine green (ICG), brilliant blue G (BBG), triamcinolone acetonide (TA), trypan blue (TB), or without dye for the treatment of idiopathic macular hole (IMH). METHODS: A search was conducted using PubMed, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) for related studies published before October 2018. RESULTS: A total of 29 studies and 2514 eyes were included in this network Meta-analysis. For IMH closure, the rank from the best to the worse treatment was: BBG, TB, TA, ICG, and no dye. There was a significant difference in postoperative IMH closure rate between BBG and no dye. The rank of the best to the worse treatment to improve visual acuity was: BBG, TB, no dye, TA, and ICG. The improvement rate of visual acuity after using BBG was significantly higher than ICG. The improvement rate of visual acuity was more favorable with TB than ICG, TA, and no dye. CONCLUSION: BBG can contribute to better anatomical and functional outcomes compared to other dyes for ILM peeling in patients with IMH. The results show that the best treatment of ILM peeling with dyes is BBG.

AIM: To compare the differences and agreement of ocular biometric parameters in highly myopic eyes obtained by optical biometric measurement instruments, the OA-2000 and IOLMaster 500. METHODS: Totally, 90 patients (90 eyes) were included. They were divided into high myopia group and control group. Ocular parameters, including axial length (AL), mean keratometry (Km), anterior chamber depth (ACD), and white to white (WTW), were obtained from the OA-2000 and IOLMaster 500. RESULTS: For the control group, we applied Bland-Altman graphs to assess the 95% limits of agreement (LoA) for most parameters including AL, ACD, Km, and WTW (-0.24 to 0.29 mm, -0.22 to 0.45 mm, -0.39 to 0.31 D, and -0.90 to 0.86 mm, respectively). In high myopia patients, AL, ACD, Km values had wider 95% LoA (-0.34 to 0.32 mm, -0.36 to 0.34 mm, -0.57 to 0.47 D, respectively), except WTW (-0.80 to 0.68 mm). Differences were not statistically significant between these two instruments (P>0.05). CONCLUSION: Most parameters obtained by the OA-2000 and IOLMaster 500 are comparable, including the AL, ACD, and K values. Among them, the agreement of the high myopia patients is poor compared to the patients without high myopia.

Decidual macrophages (dMϕ) are the second largest population of leukocytes at the maternal–fetal interface and play critical roles in maintaining pregnancy. Our previous studies demonstrated the active involvement of monoclonal nonspecific suppressor factor-β (MNSFβ) in embryonic implantation and pregnancy success. MNSFβ is a ubiquitously expressed ubiquitin-like protein that also exhibits immune regulatory potential, but its function in human dMϕ remains unknown. Here, we observed that the proportion of CD11chigh (CD11cHI) dMϕ was significantly increased in dMϕ derived from patients with recurrent pregnancy loss (RPL dMϕ) compared to those derived from normal pregnant women (Control dMϕ). The production of MNSFβ and TNFα by RPL dMϕ was also significantly increased compared to that by Control dMϕ. Conditioned medium from RPL dMϕ exerted an inhibitory effect on the invasiveness of human trophoblastic HTR8/SVneo cells, and this effect could be partially reversed by a neutralizing antibody against TNFα. Bioinformatics analysis indicated a potential interaction between MNSFβ and RC3H1, a suppressor of TNFα transcription. Immunoprecipitation experiments with human Mϕ differentiated from the human monocyte cell line Thp1 (Thp1-derived Mϕ) proved the binding of MNSFβ to RC3H1. Specific knockdown of MNSFβ in Thp1-derived Mϕ led to a marked decrease in TNFα production, which could be reversed by inhibiting RC3H1 expression. Interestingly, a significant decrease in the protein level of RC3H1 was observed in RPL dMϕ. Together, our findings indicate that aberrantly increased MNSFβ expression in dMϕ may promote TNFα production via its interaction with RC3H1, and these phenomena could result in the disruption of the immune balance at the maternal–fetal interface and thus pregnancy loss.

The maternal recognition of pregnancy is a necessary prerequisite for gestation maintenance through prolonging the corpus luteum lifespan and ensuring progesterone production. In addition to pituitary prolactin and placental lactogens, decidual derived prolactin family members have been presumed to possess luteotropic effect. However, there was a lack of convincing evidence to support this hypothesis. Here, we unveiled an essential role of uterine Notch2 in pregnancy recognition and corpus luteum maintenance. Uterine-specific deletion of Notch2 did not affect female fertility. Nevertheless, the expression of decidual Prl8a2, a member of the prolactin family, was downregulated due to Notch2 ablation. Subsequently, we interrupted pituitary prolactin function to determine the luteotropic role of the decidua by employing the lipopolysaccharide-induced prolactin resistance model, or blocking the prolactin signaling by prolactin receptor-Fc fusion protein, or repressing pituitary prolactin release by dopamine receptor agonist bromocriptine, and found that Notch2-deficient females were more sensitive to these stresses and ended up in pregnancy loss resulting from abnormal corpus luteum function and insufficient serum progesterone level. Overexpression of Prl8a2 in Notch2 knockout mice rescued lipopolysaccharide-induced abortion, highlighting its luteotropic function. Further investigation adopting Rbpj knockout and DNMAML overexpression mouse models along with chromatin immunoprecipitation assay and luciferase analysis confirmed that Prl8a2 was regulated by the canonical Notch signaling. Collectively, our findings demonstrated that decidual prolactin members, under the control of uterine Notch signaling, assisted pituitary prolactin to sustain corpus luteum function and serum progesterone level during post-implantation phase, which was conducive to pregnancy recognition and maintenance.

Background: Previous studies suggested that probiotics intervention may be one of the methods for preventing and/or treating gastric ulcer. Objective: The aim of the study was to compare the preventive effects of a spaceflight mutant Lactobacillus reuteri F-9-35 and its wild type on ethanol-induced gastric injury in rats. Design: Forty rats were randomly allocated into five groups: a normal group (NOR), ethanol group (EtOH), skim milk group (MILK), L. reuteri F-9-35 group (F935) and wild-type group (WT). The NOR and EtOH groups received 1 ml of distilled water by daily gavage for 14 days. The MILK group received 1 ml of skim milk alone, while the F935 and WT groups were administered 1 ml of skim milk containing the mutant and wild type (1 × 1010 colony-forming unit/ml) by daily gavage for 14 days, respectively. Acute gastric injury was induced by absolute alcohol 1 h after the final administration of different treatments, except for the NOR group. Results: Pretreatment with L. reuteri F-9-35, but not milk alone or milk with the L. reuteri wild type, showed significant reduction of ethanol-induced gastric injury, as evidenced by lowering of ulcer index, ulcer area (%), and histological lesion. F-9-35 decreased the levels of lipid peroxidation and myeloperoxidase and increased mucus, glutathione, and nitric oxide levels in gastric tissue. Moreover, F-9-35 inhibited the expression of proinflammatory genes including gastric tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 and decreased the activity of nuclear factor kappa B (NF-κB). Conclusion: These findings indicated that L. reuteri F-9-35 pretreatment can attenuate ethanol-induced gastric injury in rats by inhibiting oxidative stress and inflammatory response. Together, L. reuteri F-9-35 has potential preventive efficacy on gastric ulcer.

In placental mammals, reproductive success, and maternal-fetal health substantially depend on a well-being placenta, the interface between the fetus and the mother. Disorders in placental cells are tightly associated with adverse pregnancy outcomes including preeclampsia (PE), fetal growth restriction, etc. MicroRNAs (miRNAs) represent small non-coding RNAs that regulate post-transcriptional gene expression and are integral to a wide range of healthy or diseased cellular proceedings. Numerous miRNAs have been detected in human placenta and increasing evidence is revealing their important roles in regulating placental cell behaviors. Recent studies indicate that placenta-derived miRNAs can be released to the maternal circulation via encapsulating into the exosomes, and they potentially target various maternal cells to provide a hormone-like means of intercellular communication between the mother and the fetus. These placental exosome miRNAs are attracting more and more attention due to their differential expression in pregnant complications, which may provide novel biomarkers for prediction of the diseases. In this review, we briefly summarize the current knowledge and the perspectives of the placenta-derived miRNAs, especially the exosomal transfer of placental miRNAs and their pathophysiological relevance to PE. The possible exosomal-miRNA-targeted strategies for diagnosis, prognosis or therapy of PE are highlighted.

A set of multipartite orthogonal product states is locally irreducible, if it is not possible to eliminate one or more states from the set by orthogonality-preserving local measurements. An effective way to prove that a set is locally irreducible is to show that only trivial orthogonality-preserving local measurement can be performed to this set. In general, it is difficult to show that such an orthogonality-preserving local measurement must be trivial. In this work, we develop two basic techniques to deal with this problem. Using these techniques, we successfully show the existence of unextendible product bases (UPBs) that are locally irreducible in every bipartition in $d\otimes d\otimes d$ for any $d\geq 3$, and $3\otimes3\otimes 3$ achieves the minimum dimension for the existence of such UPBs. These UPBs exhibit the phenomenon of strong quantum nonlocality without entanglement. Our result solves an open question given by Halder et al. [Phys. Rev. Lett. 122, 040403 (2019)] and Yuan et al. [Phys. Rev. A 102, 042228 (2020)]. It also sheds new light on the connections between UPBs and strong quantum nonlocality.

Purpose. To investigate the outcome of pars plana vitrectomy (PPV) with suitable internal limiting membrane peeling (ILM) and air tamponade for patients with highly myopic foveoschisis-associated lamellar macular hole (MH). Methods. This retrospective interventional case series included 11 patients with highly myopic foveoschisis-associated lamellar MH who underwent PPV and indocyanine green-aided ILM peeling up to the temporal vascular arcades. Following air tamponade after surgery, all patients were instructed to maintain a face-down position. The patients were followed up for over 1 year and evaluated for MH closure and the best-corrected visual acuity before and after surgery. Results. The mean ± standard deviation values of patient age, axial length, and follow-up duration were 67.82 ± 6.54 years, 29.21 ± 1.95 mm, and 24.27 ± 8.11 months, respectively. After surgery, the lamellar MH closed in all eyes, and 10 eyes showed vision improvement at the 1-month, 3-month, and final follow-up evaluations. One patient showed decreased vision at 2 years after surgery, with patchy chorioretinal atrophy in the macular region. Myopic foveoschisis showed resolution in three eyes and alleviation in eight. Ten patients underwent cataract surgery during PPV. Conclusion. Extension of ILM peeling up to the temporal vascular arcades and air tamponade after PPV may improve the visual function and rate of MH closure for patients with highly myopic foveoschisis-associated lamellar MH.

AIM: To demonstrate the differences of retinal and choroidal structure changes in internal carotid artery (ICA) patients of China by enhanced-depth imaging optical coherence tomography (EDI-OCT). METHODS: A retrospective review was conducted of 46 patients with a diagnosis of ICA stenosis greater than 65% on only one side (the opposite ICA Stenosis had less than 40% stenosis) from June 2015 through June 2016. All of the patients were combined with amaurosis fugax, but without any abnormality with other ocular examination. Thickness and volume of choroid and retina were manually measured by EDI-OCT. Differences were compared between ICA stenosis eyes and fellow eyes. RESULTS: There were no significant differences in the retinal thickness, macular retinal nerve fiber layer (mRNFL) thickness, inner thickness, or outer retinal thickness between the ICA Stenosis group and the control group (P=0.834, 0.187, 0.552, and 0.903, respectively). The mean central choroidal thickness of the ICA Stenosis group was significantly lower than that of the control group (239.70±23.76 µm vs 257.46±22.13 µm, P

Background: Collapsin response mediator protein-2 (CRMP2) has been shown to be involved in ischemia/hypoxia (IH) injury. We determined whether CRMP2 modulates ischemic injury in the retinal of Ocular ischemic syndrome (OIS). This study was to explore the molecular mechanisms underlying OIS in a novel mice model. Methods: Experiments were performed on adult male C57/BL6 mice that received bilateral internal carotid arteries ligation for 1, 2, or 4 weeks. The mice received injection of calpeptin group before occlusion for 4 weeks or not. The expression of CRMP2 in the retinal was examined by western blotting (WB) analysis and immunohistochemical analysis (IHC). The effects of ischemic injury on retinal were evaluated by fundus examination, fundus fluorescein angiography, electroretinogram, cell counting of retinal ganglion cell (RGC), and measurement of the thickness of the retina. Results: The veins dilated after chronic ischemia. In the electroretinography, the amplitudes of a- and b-waves kept diminishing in an ischemia time-dependent manner. Moreover, the tail vein-retinal circulation time prolonged in the 1- and 2-week group. In comparison, thickness of the retina decreased gradually with the ischemia time elapsed. WB analysis showed the CRMP2 and p-CRMP2 levels decreased in the 2- and 4-week groups. The results of IHC analysis were compatible with our results of WB. The loss of RGCs, decrease of the total reaction time and reduction of CRMP2 was alleviated by intravitreal injection of calpeptin. Conclusions: These results revealed that bilateral ligation of the internal carotid artery causes retinal ischemia in mice. Moreover, CRMP2 might play a pivotal role during the ischemic injury in the retina and inhibit the cleavage of CRMP2 can ameliorate the IH injury.

Low temperature is an important abiotic stress that negatively affects morphological growth and fruit development in melon (Cucumis melo L.). Chilling stress at the seedling stage causes seedling injury and poor stand establishment, prolonging vegetative growth and delaying fruit harvest. In this study, association mapping was performed for chilling tolerance at the seedling stage on an expanded melon core collection containing 212 diverse accessions by 272 SSRs and 27 CAPSs. Chilling tolerance of the melon seedlings was evaluated by calculating the chilling injury index (CII) in 2016 and 2017. Genetic diversity analysis of the whole accession panel presented two main groups, which corresponded to the two subspecies of C. melo, melo, and agrestis. Both the subspecies were sensitive to chilling but with agrestis being more tolerant. Genome-wide association study (GWAS) was conducted, respectively, on the whole panel and the two subspecies, totally detecting 51 loci that contributed to 74 marker-trait associations. Of these associations, 35 were detected in the whole panel, 21 in melo, and 18 in agrestis. About half of the associations identified in the two subspecies were also observed in the whole panel, and seven associations were shared by both the subspecies. CMCT505_Chr.1 was repeatedly detected in different populations with high phenotypic contribution and could be a key locus controlling chilling tolerance in C. melo. Nine loci were selected for evaluation of the phenotypic effects related to their alleles, which identified 11 elite alleles contributing to seedling chilling tolerance. Four such alleles existed in both the subspecies and six in either of the two subspecies. Analysis of 20 parental combinations for their allelic status and phenotypic values showed that the elite alleles collectively contributed to enhancement of the chilling tolerance. Tagging the loci responsible for chilling tolerance may simultaneously favor dissecting the complex adaptability traits and elevate the efficiency to improve chilling tolerance using marker-assisted selection in melon.

AIM: To compare the effect of cataract surgery in renal transplantation and hemodialysis patients.METHODS: We evaluated 51 eyes of 31 renal transplantation patients, 41 eyes of 29 hemodialysis patients and 45 eyes of 32 normal control patients who received phacoemulsification and intraocular lens (IOL) implantation from January, 2000 to August, 2014 in the Beijing Friendship Hospital. Each individual underwent a blood routine and a kidney function examination. Routine ophthalmologic examination included best-corrected visual acuity (BCVA), a slit-lamp examination to detect cataract type, determination of intraocular pressure, a corneal endothelial count, and fundus examination. All patients received phacoemulsification and an IOL implantation.CONCLUSION: This study showed that the PSC was more in the renal transplantation patients. BCVA was better and fundus lesions were less frequent in the renal transplantation group than in the hemodialysis group after cataract surgery. The multiple linear regression was showed that the Hb was positively correlated with postoperative BCVA, while Cr was negatively correlated with postoperative BCVA. These results may act as indicators in predicting visual acuity for the renal transplantation and hemodialysis patients.

Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b. An evident decrease in Rap1b expression was observed in preeclamptic placentas when compared with the control placentas, which was negatively correlated with the level of miR-518b. Based on the data of in situ hybridization and immunohistochemistry showing that Rap1b exhibited similar localization with miR-518b in villous cytotrophoblast cells and column trophoblasts, we further explored their function in regulating trophoblast cell proliferation. In HTR8/SVneo cells, exogenous transfection of miR-518b reduced the expression of Rap1b, and dual-luciferase reporter assay validated Rap1b as the direct target of miR-518b. The small RNA could increase the BrdU incorporation and the ratio of cells at S phase, and enhance the phosphorylation of Raf-1 and ERK1/2. Such growth-promoting effect could be efficiently reversed by Rap1b overexpression. The data indicate that miR-518b can promote trophoblast cell proliferation via Rap1b–Ras–MAPK pathway, and the aberrant upregulation of miR-518b in preeclamptic placenta may contribute to the excessive trophoblast proliferation. The study provides new evidence to further understand the etiology of preeclampsia.

Purpose. To determine the effect of osthole on the retina in a chronic cerebral hypoperfusion (CCH) rat model and to investigate its therapeutic activity. Methods. Seventy-two rats were randomly allocated into 6 groups. CCH was induced by permanent bilateral common carotid artery occlusion (BCCAO) in five groups. Sham surgery was performed without occlusion of the artery in the sixth group (control group). Animals were administered with saline (model group), osthole (osthole-IG group), aspirin (aspirin group), or ginaton (ginaton group); the osthole-PI group was performed with peribulbar injection of osthole. Four rats in each group were sacrificed every 5 days after drug administration, and histopathology along with morphology of retina were observed. Fundus fluorescein angiography was performed before the animals were sacrificed at day 15. Retinal Akt, NF-κB, Bax, and Bcl-2 levels were assessed using immunohistochemistry, immunofluorescence, and reverse-transcription PCR; retinal injury was assessed using TUNEL in situ; retinal levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Results. Fundus fluorescein angiography revealed the retinal vascular diameter in the osthole-IG group rats to be wider than that in the model, osthole-PI, aspirin, or ginaton group rats. Histological analysis of retinal tissue revealed an increase in retinal thickness in all treatment groups, and significant improvement was noticed in the osthole-IG group. TUNEL staining revealed fewer apoptotic cells in the osthole-IG and osthole-PI groups than in the other groups. For immunohistochemistry results, in the osthole-IG group, levels of NF-κB and Akt were lower than those in the other treated groups, while levels of the ratio Bcl-2/Bax were higher. Levels of MDA were lower and levels of SOD were higher in the osthole-IG group than in the other groups. Conclusions. Osthole protects the retina from ischemia injury secondary to CCH induced by BCCAO, mainly through anti-inflammatory, antioxidant, and antiapoptotic effects.

Purpose: To evaluate the effectiveness of nursing core competency standard education in undergraduate nursing training. Methods: Forty-two nursing undergraduates from the class of 2007 were recruited as the control group receiving conventional teaching methods, while 31 students from the class of 2008 were recruited as the experimental group receiving nursing core competency standard education. Teaching outcomes were evaluated using comprehensive theoretical knowledge examination and objective structured clinical examination. Results: The performance in the health information collection, physical assessment, scenario simulation and communication in the experimental group were significantly higher than those of the control group (p

Calcineurin (CN) is a serine/threonine phosphatase which plays important roles in meiosis maturation in invertebrate oocytes; however, the role of CN in mouse oocytes is relatively unexplored. In this study, we examined the expression, localization and functional roles of CN in mouse oocytes and granulosa cells. The RT-PCR results showed that the β isoform of calcineurin A subunit (Cn A) expressed significantly higher than α and γ isoforms, and the expression of Cn Aβ mRNA obviously decreased in oocytes in which germinal vesicle breakdown (GVBD) occurred, while only B1 of calcineurin B subunit (Cn B) was detected in oocytes and stably expressed during oocytes maturation. The following fluorescence experiment showed that Cn A was mainly located in the nucleus of germinal vesicle (GV) stage oocytes and gruanlosa cells, and subsequently dispersed into the entire cytoplasm after GVBD. The decline of Cn A in oocytes suggested that it may play an important role in GVBD. To further clarify the role of calcineurin during meiotic maturation, FK506 (a calcineurin inhibitor) was used in the culture medium contained hypoxanthine (HX) which could keep mouse oocytes staying at GV stage. As expected, FK506 could induce a significant elevation of GVBD rate and increase the MPF level of denuded oocytes (DOs). Furthermore, FK506 could also play an induction role of GVBD of oocytes in COCs and follicles, and the process could be counteracted by MAPK kinase inhibitor (U0126). Above all, the results implied that calcineurin might play a crucial role in development of mouse oocytes and MPF and MAPK pathways are involved in this process.

AIM:To observe the changes of macular thickness in patients after cataract operation.METHODS: A total of 126 patients(133 eyes)were divided into two groups that were included in this study. The group(68 eyes of 64 case)with phacoemulsification combined intraocular lens implantation and(65 eyes of 62 cases)with manual small incision cataract surgery(MSICS). There was no complication before and during the surgery. Optical coherence tomography(OCT)was examined 1, 3mo before and after surgery. The visual acuity and macular thickness were compared after surgery. The SPSS 17.0 software was used for statistical analysis. The paired t-test was used before and after surgery. Independent-samples t test was used in two groups before and after surgery, α=0.05. RESULTS: The cataract phacoemulsification group: preoperative and 1mo after surgery, the mean macular thickness was 241.3±10.9μm and 279.7±16.5μm,with significant difference(PP>0.05). The mean macular thickness was 279.7±16.5μm 1mo after surgery and 245.6±12.6μm 3mo after surgery with statistical difference(PPP>0.05). One month after surgery and 3mo after surgery, the mean macular thickness were 280.7±16.8μm and 246.6±13.2μm, with statistical difference(PP values were without statistical difference(P>0.05).CONCLUSION: The macular thickness and macular edema can be found 1mo after cataract phacoemulsification and MSICS. Three months post-operatively, macular edema disappears and does not show statistical difference compared with preoperative. The increase of macular thickness has no obvious relationship with the choice of surgery.

Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.

AIM: To evaluate the efficacy and safety of nerve growth factor(NGF)on optic nerve anterior ischemic optic neuropathy.METHODS:A total of 343 eyes of 343 patients with anterior ischemic optic neuropathy were treated with mouse NGF by the dosage of 30μg qd and continuous injected for three weeks, at the same time given expanding vascular medicine and neurotrophic agent. Corrected LogMar visual acuity, visual field mean deviation(MD)values and pattern visual evoked potential(P-VEP)were recorded and analyzed. The adverse reactions in the course of treatment were analyzed in order to evaluate the safety of this method. RESULTS: The patient's vision after treatment were significantly increased compared with that before treatment, MD of visual field and P-VEP display incubation period after treatment were significantly lowered compared with that before treatment, the difference were statistically significant(PCONCLUSION: Mouse nerve growth factor combined with vasodilators and neurotrophin for the treatment of anterior ischemic optic neuropathy had satisfaction efficacy and safety.

BACKGROUND: The World Health Organization reported in 2011 that irrational use of medicines was a serious global problem that is wasteful and harmful. The worst is use of ineffective or harmful interventions which should not be used at all. However, little is known about the changes that 20 years of evidence-based medicine has made particularly in reducing use of ineffective interventions. We surveyed clinicians in China to show how often ineffective interventions were still used in practice. METHODS: 3,246 clinicians from 24 tertiary hospitals were surveyed in person and another 3,063 through an online survey between 2006-2007. The main outcomes are prescription by a clinician, and use in a patient of, an ineffective intervention and of a matched effective intervention in patients with the same disease. 129 ineffective interventions for 68 diseases were identified from the BMJ Clinical Evidence and included in the survey. One effective intervention was identified for each disease and a total of 68 effective interventions were thus also included. The frequency of use of effective interventions was used as a reference for that of ineffective intervention. RESULTS: The mean prescription rate by clinicians is 59.0% (95% confidence interval (95% CI): 58.6% to 59.4%) and 81.0% (95% CI: 80.6% to 81.4%) respectively for ineffective and effective interventions. The mean frequency of use in patients is 31.2% (95% CI: 30.8% to 31.6%) and 56.4% (95% CI: 56.0% to 56.8%) for ineffective and effective interventions respectively. The relative reduction in use of ineffective interventions as compared with that of matched effective interventions is 27.2% (95% CI: 27.0% to 27.4%) and 44.7% (95% CI: 44.3% to 45.1%) for clinician's prescription and use in patients respectively. 8.6% ineffective interventions were still routinely used in practice. CONCLUSIONS: Ineffective interventions were still commonly used. Efforts are necessary to further reduce and eventually eliminate ineffective interventions from practice.

Liquid condensation in the reservoir near a wellbore may kill gas production in gas-condensate reservoirs when pressure drops lower than the dew point. It is clear from investigations reported in the literature that gas production could be improved by altering the rock wettability from liquid-wetness to gas-wetness. In this paper, three different fluorosurfactants FG1105, FC911, and FG40 were evaluated for altering the wettability of sandstone rocks from liquid-wetting to gas-wetting using contact angle measurement. The results showed that FG40 provided the best wettability alteration effect with a concentration of 0.3% and FC911 at the concentration of 0.3%.

Preeclampsia (PE) is a pregnancy-specific syndrome manifested by on-set of hypertension and proteinuria after 20 weeks of gestation. Abnormal placenta development has been generally accepted as initial cause of the disorder. Recently, miR-195 was found to be down-regulated in preeclamptic placentas compared with normal pregnant ones, indicating possible association of this small molecule with placental pathology of preeclampsia. By far the function of miR-195 in the development of placenta remains unknown.Bioinformatic assay predicted ActRIIA as one of the targets for miR-195. By using Real-time PCR, Western blotting and Dual Luciferase Assay, we validated that ActRIIA was the direct target of miR-195 in human trophoblast cells. Transwell insert invasion assay showed that miR-195 could promote cell invasion in trophoblast cell line, HTR8/SVneo cells, and the effect could be abrogated by overexpressed ActRIIA. In preeclamptic placenta tissues, pri-miR-195 and mature miR-195 expressions were down-regulated, whereas ActRIIA level appeared to be increased when compared with that in gestational-week-matched normal placentas.This is the first report on the function of miR-195 in human placental trophoblast cells which reveals an invasion-promoting effect of the small RNA via repressing ActRIIA. Aberrant expression of miR-195 may contribute to the occurrence of preeclampsia through interfering with Activin/Nodal signaling mediated by ActRIIA in human placenta.

Maternal cigarette smoking has adverse effects on pregnancy outcomes. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is an essential cytokine for a normal pregnancy. We investigated the impact of cigarette smoke extract (CSE) on GM-CSF expression in human cytotrophoblast cells and suggested a cellular mechanism underlying the CSE-induced GM-CSF expression. An immortalized normal human trophoblast cell line (B6Tert-1) was treated with CSE. The viability and proliferation of the CSE-treated B6Tert-1 cells were evaluated, and the expression of GM-CSF in these cells was quantified at the mRNA and the protein levels by means of reverse-transcription and quantitative polymerase chain reaction (RT-qPCR); and enzyme-linked immunosorbent assay (ELISA), respectively. Human trophoblast cells treated with CSE had an increased expression of GM-CSF at both the mRNA and the protein levels. The CSE-induced GM-CSF expression was synergistically enhanced by the addition of the proteasome inhibitor MG-132, but inhibited by AG-1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase. Furthermore, CSE treatment increased the phosphorylation of the extracellular-signal regulated kinases (ERK1/2) in the trophoblast cells. The expression of other growth factors such as heparin-binding epidermal growth factor-like growth factor (HB-EGF) and vascular endothelial growth factor (VEGF) was also evaluated. Our data suggested that cigarette smoking and proteasome inhibition synergistically up-regulate GM-CSF cytokine expression by activating the EGFR signaling pathway.

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation. [ABSTRACT FROM AUTHOR]