Peripapillary atrophy area predicts the decrease of macular choroidal thickness in young adults during myopia progression.

OBJECTIVE: This study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia. METHODS AND ANALYSIS: In this longitudinal investigation, 431 eyes-342 categorised as non-high myopia (non-HM) and 89 as HM-were examined for 2 years. Participants were examined with swept-source optical coherence tomography. The macular ChT, PPA area and axial length (AL) were measured at baseline and follow-up visits. Multiple regression analysis was performed to identify factors associated with ChT changes. The areas under the receiver operating characteristic curves were analysed to ascertain the predictive capacity of the PPA area and axial elongation for the reduction in macular ChT. RESULTS: Initial measurements revealed that the average macular ChT was 240.35±56.15 µm in the non-HM group and 198.43±50.27 µm in the HM group (p<0.001). It was observed that the HM group experienced a significantly greater reduction in average macular ChT (-7.35±11.70 µm) than the non-HM group (-1.85±16.95 µm, p=0.004). Multivariate regression analysis showed that a greater reduction of ChT was associated with baseline PPA area (ß=-26.646, p<0.001) and the change in AL (ß=-35.230, p<0.001). The combination of the baseline PPA area with the change in AL was found to be effective in predicting the decrease in macular ChT, with an area under the curve of 0.741 (95% CI 0.694 to 0.787). CONCLUSION: Over 2 years, eyes with HM exhibit a more significant decrease in ChT than those without HM. Combining the baseline PPA area with the change in AL could be used to predict the decrease of macular ChT.

Development and validation of nomograms to predict clinical outcomes of preeclampsia.

Background: Preeclampsia (PE) is one of the most severe pregnancy-related diseases; however, there is still a lack of reliable biomarkers. In this study, we aimed to develop models for predicting early-onset PE, severe PE, and the gestation duration of patients with PE. Methods: Eligible patients with PE were enrolled and divided into a training (n = 253) and a validation (n = 108) cohort. Multivariate logistic and Cox models were used to identify factors associated with early-onset PE, severe PE, and the gestation duration of patients with PE. Based on significant factors, nomograms were developed and evaluated using the area under the curve (AUC) and a calibration curve. Results: In the training cohort, multiple gravidity experience (p = 0.005), lower albumin (ALB; p < 0.001), and higher lactate dehydrogenase (LDH; p < 0.001) were significantly associated with early-onset PE. Abortion history (p = 0.017), prolonged thrombin time (TT; p < 0.001), and higher aspartate aminotransferase (p = 0.002) and LDH (p = 0.003) were significantly associated with severe PE. Abortion history (p < 0.001), gemellary pregnancy (p < 0.001), prolonged TT (p < 0.001), higher mean platelet volume (p = 0.014) and LDH (p < 0.001), and lower ALB (p < 0.001) were significantly associated with shorter gestation duration. Three nomograms were developed and validated to predict the probability of early-onset PE, severe PE, and delivery time for each patient with PE. The AUC showed good predictive performance, and the calibration curve and decision curve analysis demonstrated clinical practicability. Conclusion: Based on the clinical features and peripheral blood laboratory indicators, we identified significant factors and developed models to predict early-onset PE, severe PE, and the gestation duration of pregnant women with PE, which could help clinicians assess the clinical outcomes early and design appropriate strategies for patients.

Association of macular outward scleral height with axial length, macular choroidal thickness and morphologic characteristics of the optic disc in Chinese adults.

PURPOSE: To identify the relationship of macular outward scleral height (MOSH) with axial length (AL), macular choroidal thickness (ChT), peripapillary atrophy (PPA), and optic disc tilt in Chinese adults. METHODS: In this cross-sectional study, 1088 right eyes of 1088 participants were enrolled and assigned into high myopia (HM) and non-HM groups. MOSH was measured in the nasal, temporal, superior, and inferior directions using swept-source optical coherence tomography images. The clinical characteristics of MOSH and the association of MOSH with AL, macular ChT, PPA, and tilt ratio were analysed. RESULTS: The mean age of participants was 37.31 ± 18.93 years (range, 18-86 years), and the mean AL was 25.78 ± 1.79 mm (range, 21.25-33.09 mm). MOSH was the highest in the temporal direction, followed by the superior, nasal, and inferior directions (all p < 0.001). The MOSH of HM eyes was significantly higher than that of non-HM eyes, and it was positively correlated with AL in the nasal, temporal, and superior directions (all p < 0.001). Macular ChT was independently associated with the average MOSH (B = -0.190, p < 0.001). Nasal MOSH was positively associated with the PPA area and the presence of a tilted optic disc (both p < 0.01). Eyes with a higher MOSH in the superior (odds ratio [OR] = 1.008; p < 0.001) and inferior directions (OR = 1.006; p = 0.009) were more likely to have posterior staphyloma. CONCLUSION: MOSH is an early indicator of scleral deformation, and it is correlated positively with AL and negatively with ChT. A higher nasal MOSH is associated with a larger PPA area and the presence of a tilted optic disc. Higher MOSH values in the superior and inferior directions were risk factors for posterior staphyloma. CLINICAL TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov (Reg. No. NCT03446300).

Prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Chinese girls and women aged 9 to 45 years, 2018-2020.

Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9­45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified.

A novel peptide derived from the mannose binding lectin inhibits LPS-activated TLR4/NF-κB signaling and suppresses ocular inflammation.

Uveitis is a major cause of vision impairment worldwide. Current treatments have limited effectiveness but severe complications. Mannose binding lectin (MBL) is an important protein of the innate immune system that binds to TLR4 and suppresses LPS-induced inflammatory cytokine secretion. MBL-mediated inhibition of inflammation via the TLR4 pathway and MBL-derived peptides might be a potential therapeutics. In this study, we designed a novel MBL-derived peptide, WP-17, targeting TLR4. Bioinformatics analysis was conducted for the sequence, structure and biological properties of WP-17. The binding of WP-17 to THP-1 cells was analyzed using flow cytometry. Signaling molecules were analyzed by western blotting, and activation of NF-κB was measured by immunofluorescence-histochemical analysis. Effects of WP-17 were studied in vitro using LPS-stimulated THP-1 cells and in vivo in endotoxin-induced uveitis (EIU). Our results showed that WP-17 could bind to TLR4 expressed on macrophages, thus downregulating the expression levels of MyD88, IRAK-4, and TRAF-6, and inhibiting the downstream NF-kB signaling pathway and LPS-induced expression of TNF-α and IL-6 in THP-1 cells. Moreover, in EIU rats, intravitreal pretreatment with WP-17 demonstrated significant inhibitory effects on ocular inflammation, attenuating the clinical and histopathological manifestations of uveitis, reducing protein leakage and cell infiltration into the aqueous humor, and suppressing TNF-α and IL-6 production in ocular tissues. In summary, our study provides the first evidence of a novel MBL-derived peptide that suppressed activation of the NF-кB pathway by targeting TLR4. The peptide effectively inhibited rat uveitis and may be a promising candidate for the management of ocular inflammatory diseases.

Using a combination of peripapillary atrophy area and choroidal thickness for the prediction of different types of myopic maculopathy.

PURPOSE: To analyse the topographic characteristics in macular choroidal thickness (mChT) and ocular biometry in myopic maculopathy and to explore the potential cut-off value for prediction of myopic maculopathy (MM). METHODS: All participants underwent detailed ocular examinations. MM was subdivided into thin choroid, Bruch's membrane (BM) defects, choroidal neovascularization (CNV), and myopic tractional maculopathy (MTM) according to OCT-based classification system. Peripapillary atrophy area (PPA), tilt ratio, torsion, and mChT were individually measured. RESULTS: A total of 1947 participants were included. In multivariate logistics models, older age, longer axial length, larger PPA area, and thinner average mChT were more likely to have MM and different type of MM. Female participants were more likely to have MM and BM defects. A lower tilt ratio was more likely to be associated with CNV and MTM. The area under the curve (AUC) of single tilt ratio, PPA area, torsion, and topographic of mChT for MM, thin choroid, BM Defects, CNV, and MTM were 0.6581 to 0.9423, 0.6564 to 0.9335, 0.6120 to 0.9554, 0.5734 to 0.9312, 0.6415 to 0.9382, respectively. After combining PPA area and average mChT for predicting MM, thin choroid, BM defects, CNV, and MTM, the AUC of the combination were 0.9678, 0.9279, 0.9531, 0.9213, 0.9317, respectively. CONCLUSION: Progressive and continuous PPA area expanding and thin choroid play a role in the development of myopic maculopathy. The present study showed that a combination of peripapillary atrophy area and the choroidal thickness could be used to predict MM and each type of MM.

Artificial optimization of bamboo Ppmar2 transposase and host factors effects on Ppmar2 transposition in yeast.

Mariner-like elements (MLEs) are promising tools for gene cloning, gene expression, and gene tagging. We have characterized two MLE transposons from moso bamboo, Ppmar1 and Ppmar2. Ppmar2, is smaller in size and has higher natural activities, thus making it a more potential genomic tool compared to Ppmar1. Using a two-component system consisting of a transposase expression cassette and a non-autonomous transposon cotransformed in yeast, we investigated the transposition activity of Ppmar2 and created hyperactive transposases. Five out of 19 amino acid mutations in Ppmar2 outperformed the wild-type in terms of catalytic activities, especially with the S347R mutant having 6.7-fold higher transposition activity. Moreover, 36 yeast mutants with single-gene deletion were chosen to screen the effects of the host factors on Ppmar2NA transposition. Compared to the control strain (his3Δ), the mobility of Ppmar2 was greatly increased in 9 mutants and dramatically decreased in 7 mutants. The transposition ability in the efm1Δ mutant was 15-fold higher than in the control, while it was lowered to 1/66 in the rtt10Δ mutant. Transcriptomic analysis exhibited that EFM1 defection led to the significantly impaired DDR2, HSP70 expression and dramatically boosted JEN1 expression, whereas RTT10 defection resulted in significantly suppressed expression of UTP20, RPA190 and RRP5. Protein methylation, chromatin and RNA transcription may affect the Ppmar2NA transposition efficiency in yeast. Overall, the findings provided evidence for transposition regulation and offered an alternative genomic tool for moso bamboo and other plants.

Choroidal Thickness and Its Association With Age, Axial Length, and Refractive Error in Chinese Adults.

Purpose: To identify the association between the choroidal thickness (ChT) with age and axial length (AL) under different refractive errors (REs) in Chinese adults. Methods: Swept-source optical coherence tomography was used to measure ChT in 2126 right eyes of 2126 participants. The participants were classified as having pathologic myopia (PM), high myopia without PM (HM), low myopia (LM), and nonmyopia (non-M) according to their REs and META-PM (the Meta-Analysis of Pathologic Myopia) classification criteria. Results: The mean age was 52.49 ± 20.39 years (range, 18-93 years), and the mean RE was -5.27 ± 5.37 diopters (D; range, -25.5 to +7.75 D). The mean average ChT was 159.25 ± 80.75 µm and decreased in a linear relationship from non-M to PM (190.04 ± 72.64 µm to 60.99 ± 37.58 µm, P < 0.001). A significant decline in ChT was noted between 50 and 70 years (r = -0.302, P < 0.001) and less rapidly after the age of 70 years (r = -0.105, P = 0.024). No correlation was noted between age and ChT under 50 years (P = 0.260). A significantly higher association with AL was noted in the central fovea (ßHM = -23.92, ßLM = -23.88, ßNon-M = -18.80, all P < 0.001) and parafoveal ChT (ßHM = -22.87, ßLM = -22.31, ßNon-M = -18.61, all P < 0.001) when compared with the perifoveal region (ßHM = -19.80, ßLM = -18.29, ßNon-M = -13.95, all P < 0.001). Within each group of PM, HM, LM, and non-M, regression analysis showed that the coefficients of age and AL with different macular regions of ChT varied significantly. Conclusions: ChT was negatively correlated with age after 50 years. The thinning of the choroid was more prominent in the center and parafoveal regions as AL increased. Varied distributions of ChT decrease associated with AL and age were noted among different refractive groups.

Morphological characteristics of the optic nerve head and impacts on longitudinal change in macular choroidal thickness during myopia progression.

PURPOSE: The aim of this study was to investigate the association between morphological characteristics of Bruch's membrane opening distance (BMOD), border length (BL), border tissue angle (BTA), peripapillary atrophy (PPA) as well as axial length (AL) and incident decreased macular choroidal thickness (mChT) in young healthy myopic eyes. METHODS: A total of 323 participants aged 17-30 years were included in the current 2-year longitudinal study. Each participant underwent detailed ocular examinations at baseline and follow-up. Data of AL, refraction error, PPA area, BMOD, BL, BTA and mChT were measured individually. Incident decreased mChT was defined as follow-up mChT of participants decreased into the lowest quartile of baseline mChT. RESULTS: Subjects with longer AL, longer BMOD were more likely to have incident decreased mChT (odds ratio [OR], 1.56; 2.09, respectively, per 1 Z-score increment), whereas larger BTA was less likely to develop decreased mChT (odds ratio [OR], 0.51, per 1 Z-score increment). The area under the receiver operating curve (AUROC) of basic risk model for incident decreased mChT was 0.6284. After adding BMOD, BTA and AL separately to the basic risk model, the AUROC of the combination could reach 0.6967, 0.6944 and 0.7383, respectively. After combining BMOD, BTA and AL to the basic model, the AUROC of the combination showed the highest AUROC of 0.7608. CONCLUSIONS: Bruch's membrane opening distance and AL are significant risk factors for incident decreased mChT, whereas BTA played protective role in the deterioration of mChT. In addition, a combination of BMOD, BTA and AL could serve as earlier predictors of the attenuation of mChT in myopia progression.

Simulation Studies Provide Evidence of Aerosol Transmission of SARS-CoV-2 in a Multi-Story Building via Air Supply, Exhaust and Sanitary Pipelines.

A cross-layer non-vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in a quarantine hotel in Guangzhou, Guangdong Province, China in June 2021. To explore the cross-layer transmission path and influencing factors of viral aerosol, we set up different scenarios to carry out simulation experiments. The results showed that the air in the polluted room can enter the corridor by opening the door to take food and move out the garbage, then mix with the fresh air taken from the outside as part of the air supply of the central air conditioning system and re-enter into different rooms on the same floor leading to the same-layer transmission. In addition, flushing the toilet after defecation and urination will produce viral aerosol that pollutes rooms on different floors through the exhaust system and the vertical drainage pipe in the bathroom, resulting in cross-layer vertical transmission, also aggravating the transmission in different rooms on the same floor after mixing with the air of the room and entering the corridor to become part of the air supply, and meanwhile, continuing to increase the cross-layer transmission through the vertical drainage pipe. Therefore, the air conditioning and ventilation system of the quarantine hotel should be operated in full fresh air mode and close the return air; the exhaust volume of the bathroom should be greater than the fresh air volume. The exhaust pipe of the bathroom should be independently set and cannot be interconnected or connected in series. The riser of the sewage and drainage pipeline of the bathroom should maintain vertical to exhaust independently and cannot be arbitrarily changed to horizontal pipe assembly.

Distribution and association of visual impairment with myopic maculopathy across age groups among highly myopic eyes - based on the new classification system (ATN).

PURPOSE: To investigate the percentages and risk factors for visual impairment (VI) across age groups in a highly myopic cohort with a wide range of age (18-93 years). METHODS: A total of 2099 eyes (1220 participants) were enrolled. All participants underwent detailed ocular examinations. Myopic maculopathy (MM) was assessed as myopic atrophy maculopathy (MAM), myopic traction maculopathy (MTM) or myopic neovascular maculopathy (MNM) based on the ATN system. RESULTS: Most participants younger than 50 years had normal vision, while the cumulative risk of VI and blindness gradually increased after 50-59 years. The percentage of each type of MM increased nonlinearly with ageing (all p < 0.001), with an accelerated period of increase after 45 years for MAM, and after 50 years for MTM and MNM. Axial length (AL) ≥30 mm was the only associated factor for mild VI or worse in participants aged 18-39 years (p < 0.001). Older age, AL ≥30 mm and the presence of MAM were predictors for mild VI or worse in the group aged 40-49 years (all p < 0.05). In participants aged ≥50 years, older age, female sex, longer AL and increased severity of MM were risk factors for VI and blindness (all p < 0.05). CONCLUSION: The percentages of MM and related VI increased nonlinearly with older age, with a turning point at 45 years for MAM, preceding that of MTM, MNM and VI by 5 years, warranting future longitudinal studies to confirm. Different age groups presented different risk factors for VI. Timely screening should be in place for middle-aged high myopes.

Laboratory management for large-scale population screening for SARS-CoV-2.

INTRODUCTION: The aim of this study was to investigate the improvements in laboratory testing procedures and the quality and safety management for large-scale population screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Because of epidemic prevention and control needs in Hebei Province, on January 7, 2021, the Health Commission of Zhejiang Province sent a medical team to Hebei Province, to carry out SARS-CoV-2 nucleic acid testing. Screening for the SARS-CoV-2 nucleic acid test was performed using reverse-transcription polymerase chain reaction (RT-PCR). Practical tests and repeated process optimization were adopted to explore the optimal solution for improving laboratory testing procedures and the quality of and safety management for large-scale population screening for SARS-CoV-2. RESULTS: The Zhejiang medical team completed 250,000 pooled SARS-CoV-2 nucleic acid samples in 24 days in Shijiazhuang, with a peak daily testing capacity of 40,246 samples testing. There were no false-negative or false-positive results, and no laboratory personnel was infected with SARS-CoV-2. Significant achievements have been made in SARS-CoV-2 prevention and control. CONCLUSIONS: This report summarizes the effort of the medical team regarding their management of the quality and safety of laboratory tests and proposes corresponding empirical recommendations to provide a reference for future large-scale population screening SARS-CoV-2.

The interleukin 6 trans-signaling increases prostaglandin E2 production in human granulosa cells†.

As a potent autocrine regulator, the proinflammatory cytokine interleukin 6 (IL6) is expressed in granulosa cells and is involved in the modulation of various follicular functions, including follicular development and ovulation. At present, the detailed molecular mechanisms by which IL6 regulates the event of ovulation remain to be elucidated. In the present study, primary and immortalized (SVOG) human granulosa-lutein (hGL) cells were used to investigate the effects of IL6 on the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and the subsequent synthesis of prostaglandin E2 (PGE2) and to investigate the underlying molecular mechanisms. We found that instead of classic signaling, IL6/soluble form of the IL6 receptor (sIL-6Ralpha) trans-signaling induced the expression of PTGS2 and production of PGE2 in both SVOG cells and primary hGL cells. Moreover, IL6/sIL-6Ralpha activated the phosphorylation of Janus-activated kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which in turn induced STAT3 nuclear translocation. In addition, these effects were suppressed by the addition of inhibitors (AG490 for JAK2 and C188-9 for STAT3) and by the small interfering RNA-mediated knockdown of STAT3. In addition, suppressor of cytokine signaling 3 (SOCS3) acts as a negative-feedback regulator in IL6/sIL-6Ralpha-induced cellular activities, including the activation and nuclear translocation of STAT3, upregulation of PTGS2 expression, and increase in PGE2 production in SVOG cells. In conclusion, IL6 trans-signaling upregulates the expression of PTGS2 and increases the production of PGE2 via the JAK2/STAT3/SOCS3 signaling pathway in hGL cells. Our findings provide insights into the molecular mechanisms by which IL6 trans-signaling may potentially modulate the event of ovulation in human ovaries.

Morphological differences between two types of Bruch's membrane defects in pathologic myopia.

PURPOSE: To investigate morphological differences between two types of Bruch's membrane (BM) defects-patchy atrophy (PA) and CNV-related macular atrophy (CNV-MA) METHODS: Eyes presenting with PA or CNV-MA were included. Scleral thickness (ST), choroidal thickness (CT), and scleral morphological characteristics were obtained by swept-source optical coherence tomography (SS-OCT). Fundus photographs were performed to measure the size of PA and CNV-MA lesions. RESULTS: Among a total of 167 eyes evaluated, 106 eyes had PA and 61 eyes had CNV-MA. In addition, dome-shaped macula (DSM) was identified in 20 (18.87%) and 10 (16.39%) eyes among PA and CNV-MA, respectively. The eyes of CNV-MA without DSM showed a thicker subfoveal ST (278.61 ± 56.17 vs 231.58 ± 66.09 mm, P < 0.001), a thinner subfoveal CT, and a higher rate of scleral perforating vessels (70.6% vs 50.0%, P = 0.021) when compared with those of PA without DSM. The size of PA/CNV-MA lesions was associated with CT in eyes without DSM. However, it was only associated with bulge height in eyes with DSM (r = 0.5, P = 0.013). CONCLUSIONS: The eyes with CNV-MA had a thicker sclera than those with PA, which add another evidence to indicate the absence of the progressive relationship between two types of BM defects. The enlargement of lesions in BM defects between eyes with and without DSM may be caused by different mechanical forces. SS-OCT, which focuses on scleral and choroid morphology, may be necessary for more accurate classification of pathologic myopia.

GDF8 Promotes the Cell Invasiveness in Human Trophoblasts by Upregulating the Expression of Follistatin-Like 3 Through the ALK5-SMAD2/3 Signaling Pathway.

Growth differentiation factor 8 (GDF8) and its antagonist follistatin-like 3 (FSTL3) are expressed in the placenta during early pregnancy. These two factors may have a role to play in the regulation of normal placentation. However, whether GDF8 can regulate the expression of FSTL3 in human trophoblasts remains to be elucidated. In this study, we aimed to investigate the effects of GDF8 on the expression of FSTL3 and the underlying molecular mechanisms using human trophoblasts as a study model. Our results showed that GDF8 significantly upregulates the expression and production of FSTL3, which further promotes cell invasiveness in immortalized extravillous cytotrophoblast cells and primary extravillous cytotrophoblast cells obtained from human first-trimester placentae. Additionally, using an siRNA-mediated knockdown approach, we found that this regulatory effect is most likely mediated by the ALK5-Sma- and Mad-related protein (SMAD)2/3-induced signaling pathway. These findings deepen our understanding of the functional roles of GDF8 and FSTL3 in the regulation of cell invasiveness of trophoblasts.

Morphologic Features of Myopic Choroidal Neovascularization in Pathologic Myopia on Swept-Source Optical Coherence Tomography.

Purpose: To investigate the morphologic features and identify the risk factors of myopic choroidal neovascularization (CNV). Methods: Eighty-eight eyes of 69 consecutive patients with myopic CNV were included in this study. About 109 eyes of 78 pathologic myopia patients without myopic CNV were randomly selected as the control group. Morphologic features and parameters including scleral thickness (ST), choroidal thickness (CT), posterior staphyloma height and the presence of scleral perforating vessels were obtained and measured by swept-source optical coherence tomography (SS-OCT). Binary logistic regression analysis was performed to identify the risk factors for myopic CNV. Results: Patients with myopic CNV had relatively shorter axial length (P < 0.001) and thicker sclera (P < 0.001) compared to those without. After adjusting age, gender and axial length, thick sclera (OR = 1.333, P < 0.001 per 10-µm increase) and thin choroid (OR = 0.509, P < 0.001 per 10-µm increase) were associated with the presence of myopic CNV. Scleral perforating vessels were detected in the area of myopic CNV in 78.67% of the subjects. Conclusions: A relatively thicker sclera and a thinner choroid are the biological indicators for myopic CNV on SS-OCT. Scleral perforating vessels may also play a pivotal role in the formation of myopic CNV.

Follistatin-like 3, an activin A binding protein, is involved in early pregnancy loss.

BACKGROUND: Early pregnancy loss (EPL), a common and severe complication in pregnancy, has a long-term personal and social impact. It was previously reported that follistatin-like 3(FSTL3), an activin A binding protein, contributes to the invasion and migration of trophoblast. Simultaneously, activin A induces the release of FSTL3 and the elevated activin A is found to be associated with pregnancy loss in women. This study aimed to identify the roles of FSTL3 in the establishment and maintenance of pregnancy, and to determine whether FSTL3 is involved in the pathophysiology of EPL. METHODS: Endometrial Ishikawa cells and JAR cells were cultured and FSTL3 siRNA was used to silence FSTL3. The trophoblast spheroids mimicking embryos were used in an embryonic adhesion system. The system aimed to investigate the role of FSTL3 silence on embryonic adhesion onto endometrial cell in vitro. The ICR mice model in vivo was used to investigate whether the FSTL3 works in embryonic implantation. The western blotting was used to determine the expression of FSTL3 and activin A. RESULTS: In the in vitro study, silence of FSTL3 in JAR cells significantly reduced the number of trophoblast spheroids adhered onto Ishikawa cells compared with the scramble siRNA. For the in vivo study, the number of embryos implanted in the uterine horn injected with FATL3 siRNA mixture was significantly less than that in control group. In the case control study, both the expression of FSTL3 and activin A in EPL women were significantly higher than that in controls. CONCLUSIONS: FSTL3 plays a biological role in the establishment and maintenance of normal pregnancy. Moreover, FSTL3 may be involved in the early pregnancy loss via neutralizing the elevated activin A.

Declined placental PLAC1 expression is involved in preeclampsia.

BACKGROUND: This study aimed to clarify the change of the expression of placenta-specific 1 (PLAC1) in the placenta of preeclamptic women and to explore the regulatory effects on thophoblast by PLAC1. METHODS: Nineteen women with preeclampsia and 19 with normal pregnancies were recruited, and then we determined the expression of PLAC1 by immunohistochemistry (IHC) and Western blotting. To observe the effect of hypoxia on the expression of PLAC1, trophoblasts were cultured at the normoxia or hypoxia condition. Small interference of ribonucleic acid (siRNA) was used to silence PLAC1. The proliferation, migration and invasion of trophoblasts were evaluated with cell counting kit-8 and transwell analysis, and the apoptosis of trophoblast was evaluated by flow cytometry with FITC and PI staining. RESULTS: Placental PLAC1 expression was significantly decreased in severe preeclampsia compared with control (P < .001). The expression of PLAC1 in trophoblasts was significantly decreased after treated with low oxygen concentration (P = .018). PLAC1 siRNA significantly inhibited the proliferation (P < .001), the migration (P < .001) and invasion (P < .001) of trophoblasts, but increased the apoptosis (P = .004 for Swan-71; P = .031 for Jar). CONCLUSIONS: The expression of PLAC1 was declined in preeclampsia and this inhibited the function of trophoblast, suggesting PLAC1 may play a role in the development of preeclampsia.

Involvement of follistatin-like 3 in preeclampsia.

INTRODUCTION: Preeclampsia is a main cause of maternal and perinatal mortality and morbidity. The expression of follistatin-like 3 (FSTL3) is enhanced in maternal serum and placenta of preeclamptic women. However, whether FSTL3 is involved in the pathophysiologic of preeclampsia has not been clarified yet. METHOD: Trophoblast cell lines Swan71 and JAR cells were cultured and siRNA was used to silence FSTL3. The expression of FSTL3 was determined by Western blotting. The matrigel-coated transwell and wound healing assays were used to assess invasion and migration, cell proliferation and apoptosis were detected by CCK-8 and flow cytometric analysis, respectively. Oil red O staining was used to detect the lipid storage in trophoblast. RESULTS: Hypoxia culture significantly enhanced the expression of FSTL3 by trophoblast. Down-regulation of FSTL3 significantly suppressed the proliferation, migration, invasion and lipid storage but increased apoptosis of trophoblast. DISCUSSION: Aberrant expression of FSTL3 in preeclampsia led to the dysfunction of trophoblast, indicating its involvement in the pathogenesis of preeclampsia.

Alteration in methylation level at differential methylated regions of MEST and DLK1 in fetus of preeclampsia.

OBJECTIVES: Offspring born to preeclamptic women are at high risk for metabolic diseases in later life, but the mechanisms are not known. The purposes of the current investigation were to clarify the changes in DNA methylation at MEST and DLK1 DMRs in fetus of preeclampsia and to explore the possible mechanisms behind the high risk of adult diseases in the offspring of preeclampsia. METHODS: Fetal lymphocytes were isolated from umbilical cord blood of 78 women with preeclampsia and 95 women with normal pregnancy. Genomic DNA was extracted and then DNA methylation levels of MEST and DLK1 DMRs were determined by MassARRAY quantitative methylation analysis. RESULTS: The methylation levels were detected in 20 CpG sites of MEST DMR and 16 sites of DLK1 DMR. Methylation changes were significantly different at CPG1, 3, 4, 7.8, 15, 18.19, and 20 of MEST between preeclampsia and normal pregnancy (P = 0.014, 0.001, <0.001, <0.001, = 0.001,  = 0.005, and = 0.003, respectively). Significant differences were also observed at CPG 3 and 9 of DLK1 (P = 0.002 and 0.027, respectively). However, overall methylation at these DMRs were not affected. CONCLUSION: We conclude methylation changes at some CpG sites of MEST and DLK DMRs in preeclamptic group. This may be among the mechanisms behind the high risk of adult diseases in the later life of offspring born to preeclamptic pregnancies. ABBREVIATIONS: DMR: Differentially Methylated Region; MEST: Mesoderm Specific Transcript.