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Fundus imaging plays a pivotal role in diagnosing retinal and choroidal diseases. Optical coherence tomography angiography (OCTA), by capturing signals to reconstruct vascular structures, offers a clear depiction of retinal vasculature with notable advantages such as rapid scanning and non-invasiveness. Although OCTA, due to its underlying principles, cannot dynamically assess vascular function, exploring its future applications and potential to eventually replace traditional fundus angiography remains a key focus in the medical community. OCTA provides multiple parameters that conventional fundus angiography cannot obtain. With the expanding coverage area of OCTA scans and improvements in artifact elimination, the detection rate of various retinal and choroidal diseases has significantly increased, making the widespread clinical application of OCTA an inevitable trend. Although ultra-widefield OCTA cannot yet fully replace angiography in clinical practice, with continued clinical practice, expanded clinical research, and ongoing technological innovation, OCTA is expected to gradually replace fundus angiography in the future.

Ectomycorrhizal symbiosis, which involves mutually beneficial interactions between soil fungi and tree roots, is essential for promoting tree growth. To establish this symbiotic relationship, fungal symbionts must initiate and sustain mutualistic interactions with host plants while avoiding host defense responses. This study investigated the role of reactive oxygen species (ROS) generated by fungal NADPH oxidase (Nox) in the development of Laccaria bicolor/Populus tremula × alba symbiosis. Our findings revealed that L. bicolor LbNox expression was significantly higher in ectomycorrhizal roots than in free-living mycelia. RNAi was used to silence LbNox, which resulted in decreased ROS signaling, limited formation of the Hartig net, and a lower mycorrhizal formation rate. Using Y2H library screening, BiFC and Co-IP, we demonstrated an interaction between the mitogen-activated protein kinase LbSakA and LbNoxR. LbSakA-mediated phosphorylation of LbNoxR at T409, T477 and T480 positively modulates LbNox activity, ROS accumulation and upregulation of symbiosis-related genes involved in dampening host defense reactions. These results demonstrate that regulation of fungal ROS metabolism is critical for maintaining the mutualistic interaction between L. bicolor and P. tremula × alba. Our findings also highlight a novel and complex regulatory mechanism governing the development of symbiosis, involving both transcriptional and posttranslational regulation of gene networks., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Formate is a major reactive carbon species in one-carbon metabolism, where it serves as an endogenous precursor for amino acid and nucleic acid biosynthesis and a cellular source of NAD(P)H. On the other hand, aberrant elevations in cellular formate are connected to progression of serious diseases, including cancer and Alzheimer's disease. Traditional methods for formate detection in biological environments often rely on sample destruction or extensive processing, resulting in a loss of spatiotemporal information. To help address these limitations, here we present the design, synthesis, and biological evaluation of a first-generation activity-based sensing system for live-cell formate imaging that relies on iridium-mediated transfer hydrogenation chemistry. Formate facilitates an aldehyde-to-alcohol conversion on various fluorophore scaffolds to enable fluorescence detection of this one-carbon unit, including through a two-color ratiometric response with internal calibration. The resulting two-component probe system can detect changes in formate levels in living cells with a high selectivity over potentially competing biological analytes. Moreover, this activity-based sensing system can visualize changes in endogenous formate fluxes through alterations of one-carbon pathways in cell-based models of human colon cancer, presaging the potential utility of this chemical approach to probe the continuum between one-carbon metabolism and signaling in cancer and other diseases.

Aim: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH., Methods: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point., Results: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P =0.014)., Conclusion: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery., Competing Interests: Conflicts of Interest: Cai Y, None; Liu WB, None; Wei D, None; Deng X, None; Li XX, None; Zhao MW, None; Shi X, None; Liang JH, None., (International Journal of Ophthalmology Press.)

In recent years, α-In 2 Se 3 has attracted great attention in miniaturizing nonvolatile random memory devices because of its room temperature ferroelectricity and atomic thickness. In this work, we construct two-dimensional (2D) van der Waals (vdW) heterostructures α-In 2 Se 3 /MoS 2 with different ferroelectric polarization and design a 2D graphene (Gr)/In 2 Se 3 /MoS 2 /Gr ferroelectric tunnel junction (FTJ) with the symmetric electrodes. Our calculations show that the band alignment of the heterostructures can be changed from type-I to type-II accompanied by the reversal of the ferroelectric polarization of In 2 Se 3 . Furthermore, the ferroelectricity persists in Gr/In 2 Se 3 /MoS 2 /Gr vdW FTJs, and the presence of dielectric layer MoS 2 in the FTJs enables the effective modulation of the tunneling barrier by altering the ferroelectric polarization of α-In 2 Se 3 , which results in two distinct conducting states denoted as "ON" and "OFF" with a large tunneling electroresistance (TER) ratio exceeding 10 5 %. These findings suggest the importance of ferroelectric vdW heterostructures in the design of FTJs and propose a promising route for applying the 2D ferroelectric/semiconductor heterostructures with out-of-plane polarization in high-density ferroelectric memory devices.

Multidrug resistance severely limits the efficacy of ovarian cancer (OC) treatment. Recent studies have revealed the carcinogenic role of LINC00707 RNA. However, the role of LINC00707 in the development of multidrug resistance in OC has not been clarified. Therefore, the aim of this study was to investigate the relationship between LINC00707 and multidrug resistance in OC, which can facilitate the development of new therapeutic agents for effectively addressing this issue. The RNA expression of LINC00707, miR-382-5p and leucine-rich repeat kinase 2 (LRRK2) in SKOV3 (a human OC cell line) cells was detected by qRT-PCR. The effects of LINC00707 on the proliferation and viability of SKOV3 cells were determined by MTT assay and colony formation assay. The interaction of LINC00707, miR-382-5p, and LRRK2 was bioinformatically predicted and verified with dual-luciferase reporter assay. In addition, the effect of LINC00707 on drug resistance in SKOV3 cells through targeting the miR-382-5p/LRRK2 axis was explored. The expression of LINC00707 and LRRK2 was significantly increased in SKOV3 cells, while miR-382-5p expression was significantly decreased. The results of bioinformatic prediction and colony formation assay demonstrated that LINC00707 could regulate LRRK2 expression in SKOV3 cells by targeting miR-382-5p. Additionally, knockdown of LINC00707 markedly increased expression of miR-382-5p and decreased that of LRRK2, increased cell proliferation and viability, as well as sensitivity to chemotherapeutic agents in SKOV3 cells. Notably, these manifestations were more obvious with simultaneous knockdown of LINC00707 and miR-382-5p compared with knockdown of LINC00707 alone. LINC00707 is overexpressed in SKOV3 cells and promotes SKOV3 cell proliferation and resistance to chemotherapeutic drugs via targeting the miR-382-5p/LRRK2 axis.

With the explosion of data-centric applications, new in-memory computing technologies, based on nonvolatile memory devices, have become competitive due to their merged logic-memory functionalities. Herein, employing first-principles quantum transport simulation, we theoretically investigate for the first time the electronic and contact properties of two types of monolayer (ML)-MoS 2 ferroelectric field-effect transistors (FeFETs) integrated with ferroelectric BiAlO 3 (0001) (BAO(0001)) polar surfaces. Our study finds that the interfacial properties of the investigated partial FeFET devices are highly tunable by switching the electric polarization of the ferroelectric BAO(0001) dielectric. Specifically, the transition from quasi-Ohmic to the Schottky contact, as well as opposite contact polarity of respective n-type and p-type Schottky contact under two polarization states can be obtained, suggesting their superior performance metrics in terms of nonvolatile information storage. In addition, due to the feature of (quasi-)Ohmic contact in some polarization states, the explored FeFET devices, even when operating in the regular field-effect transistor (FET) mode, can be extremely significant in realizing a desirable low threshold voltage and interfacial contact resistance. In conjunction with the formed van der Waals (vdW) interfaces in ML-MoS 2 /ferroelectric systems with an interlayer, the proposed FeFETs are expected to provide excellent device performance with regard to cycling endurance and memory density.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wang, Guo, Zhao, Song, Guo, Duan, Yan and Zheng.)

Aim: To investigate changes of choroidal thickness (ChT) in children with myopia and the effect of current myopia control interventions on ChT., Methods: Major literature databases were searched for studies relevant to myopia in children. All studies used swept-source optical coherence tomography (SS-OCT) or enhanced depth imaging optical coherence tomography (EDI-OCT) to measure the ChT value. The weighted mean difference (WMD) and 95% confidence interval (CI) were pooled to evaluate ChT in myopia children., Results: A total of 11 eligible articles, including 1693 myopic and 1132 non-myopic eyes, were included in the first Meta-analysis. The sub-foveal choroidal thickness (SFCT; WMD=-40.06, 95%CI, -59.36 to -20.75, P <0.001) and ChT at other sectors were significantly thinner in myopic eyes compared with the non-myopic eyes. The Meta-analysis revealed that the ChT decreased horizontally from the temporal sector toward the nasal sector in the pediatric myopia population. Another 11 studies reporting the effect of myopia control interventions were included in the second Meta-analysis for the relationship between myopia control treatments and ChT. SFCT significantly increased after orthokeratology (OK) treatment and OK combined with 0.01% atropine (OKA) treatment (WMD=19.47, 95%CI, 15.96 to 22.98, P <0.001; WMD=21.81, 95%CI, 12.92 to 29.70, P <0.001, respectively). The forest plots showed that SFCT changed little in myopic children receiving 0.01% atropine ( P =0.30). Furthermore, the Meta-analysis showed that OK treatment had a stronger effect on the value of SFCT in myopic children as compared with 0.01% atropine (WMD=9.86; 95%CI, -0.21 to 19.93, P =0.05). There is no difference between the treatment with OK and OKA treatment in ChT in myopic children ( P =0.37)., Conclusion: The ChT in myopic eyes is thinner than that in non-myopic eyes in pediatric population. Myopia control interventions including OK and OKA lead to ChT thickening, but other treatments such as 0.01% atropine did not show an increase in ChT., (International Journal of Ophthalmology Press.)

Purpose: This study investigated the correlation between corneal biomechanical parameters and the speed of myopia progression., Methods: This is a retrospective, multicenter study. Both Chinese and Caucasian children were involved. The follow-up time was at least 12 months. Ocular biometry data including the central corneal thickness (CCT), axial length (AL), corneal keratometry (K), anterior chamber depth (ACD), white-to-white (WTW) distance, and pupil size (PS) were measured. The age of onset, speed of progression of spherical equivalent (SE), and speed of AL elongation were calculated. Data were analyzed using the R programming language., Results: This study comprised 306 eyes of 153 myopic children. 122 children were Chinese, and 31 children were Caucasian. The myopia progression was faster in Chinese children than that in the Caucasian group in both SE progression speed and AL elongation speed. The CCT was negatively correlated with the SE speed of progression (correlation coefficient, R  = -0.65, and p =7.25 × 10 -38 ) and AL speed ( R  = -0.47 and p =1.62 × 10 -18 ). CCT was positively correlated with the age of onset ( R  = 0.35 and p =4.53 × 10 -10 ). No significant correlation ( R  > 0.3 and p < 0.01) was found between other ocular biometries (K, ACD, WTW, and PS) and the onset and speed of the progression of myopia. The same trends were found in both Chinese and Caucasian children and in both the right eye and left eye., Conclusion: CCT was negatively correlated with myopia (SE) progression speed and AL elongation speed. Thin CCT may be associated with faster myopia progression., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Peng Zhou et al.)

Osteoporosis is a generalized disease of bone that leads to a loss of bone density and bone mass, destruction of bone microstructure, increased brittleness and therefore fracture. At present, the main treatment of Western medicine is drug therapy such as bisphosphonates, calcitriol, vitamin D, etc. However, long-term use of these drugs may bring some adverse reactions. Chinese herbal medicine Cistanche deserticola could regulate bone metabolism by promoting osteoblast activity and inhibiting osteoclast activity with low toxicity and adverse reactions. Therefore, Cistanche deserticola has attracted increasing attention for its efficacy in the prevention and treatment of osteoporosis in recent years. Here we present a literature review of the molecular pathways involved in osteoporosis and the effects of Cistanche deserticola on bone metabolism. Our objective is to clarify the mechanism of Cistanche deserticola in the treatment of osteoporosis., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity., Methods: The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records., Results: The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs . 46.00%, P =0.043; 16.11%±10.35% vs . 12.06%±6.47%, P =0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group ( P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs . 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood ( P =0.011, P =0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs . 12.00 (4.00-101.00) mg/L, P =0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs . 10.46 (2.50-25.73) g/L, P =0.000 3], and higher blood platelet count (PLT) [(205.87×10 9 ±67.98×10 9 ) /L vs . (164.57×10 9 ±69.57×10 9 ) /L, P =0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs . 2.05 (0.42-4.36) g/L, P =0.014]., Conclusion: The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.

Aim: To evaluate the outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for patients with retinal vein occlusion (RVO) related-macular edema (ME) in Tibetan., Methods: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients (93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People's Hospital from Jan 2018 to December 2019 were collected., Results: The mean patient age was 56.8±10.6y, 45 (50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity (BCVA) significantly increased (52.2±21.8 letters) in comparison with the baseline (38.2±24.1 letters, P <0.001); while the central retinal thickness (CRT) significantly reduced (245.5±147.6 µm) in comparison with the baseline (504.1±165.2 µm, P <0.001). The 43.0% of the eyes gained ≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted., Conclusion: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME., (International Journal of Ophthalmology Press.)

Aim: To compare ultra-widefield (24×20 mm 2 ) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions., Methods: Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm 2 ) were performed., Results: Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm 2 vs 0.287±0.108 mm 2 , P =0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm 2 on SS-OCTA and FA, respectively ( P =0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images ( P =0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm 2 , P =0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA ( P <0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability., Conclusion: Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation., (International Journal of Ophthalmology Press.)

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (β=-0.521, P =0.036); patients aged ≥64 years had lower PCS than those aged<55 years (β=-0.636, P =0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (β=1.063, P <0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (β=-0.860, P =0.002), while the PCS of those with severe clinical symptoms was much lower (β=-1.126, P <0.001). Patients treated with combination therapy had higher PCS than untreated patients (β=0.731, P =0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (β=-0.712, P =0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (β=-1.183, P =0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

Polysaccharides have attracted much attention in the food industry due to their diverse biological activities. To date, research on the mechanism of polysaccharide synthesis has mainly focused on the role of crucial enzymes in the polysaccharide synthesis pathway, but other genes that regulate polysaccharide synthesis have not been well explored. In this study, the GlPP2C1 gene, encoding a phosphoprotein type 2C phosphatase, was cloned, and PP2C-silenced strains (PP2C1i-1 and PP2C1i-3) were screened. Measurements of the polysaccharide content and cell wall tolerance revealed that GlPP2C1 silencing increased the polysaccharide content and enhanced cell wall resistance in Ganoderma lingzhi. The contents of intracellular polysaccharides (IPS), extracellular polysaccharides (EPS) and β-1,3-D-glucan in PP2C-silenced strains were increased by 25%, 33% and 36%, respectively, compared with those in the WT strains and strains transformed with an empty vector. Further mechanistic studies showed that GlPP2C1 silencing increased the content of Ganoderma lingzhi polysaccharides (GL-PS) through Slt2. In summary, this study revealed the mechanism through which protein phosphatase regulates GL-PS biosynthesis for the first time.

Aim: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR)., Methods: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family., Results: Two novel mutations of DOCK6 (c.1396C>T and c.4796G>A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents., Conclusion: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist., (International Journal of Ophthalmology Press.)

Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA)., Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly., Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02)., Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Liu, Zhou, Jin, Sun, Zhao, Han, Qu, Shi and Zhao.)

Purpose: To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC)., Methods: We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts., Results: The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression., Conclusions: Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.

Objective: To identify prognostic factors for revitrectomy in patients who underwent pars plana vitrectomy (PPV) for complications with proliferative diabetic retinopathy (PDR). Methods: This study was a retrospective case-control study. Clinical data of PDR patients (290 eyes) at Peking University People's Hospital from December 2019 to December 2020 were retrospectively collected.According to the number of operations, patients were divided into two groups: single PPV group (227 eyes) and revitrectomy PPV group (63 eyes). Follow-up will be conducted up to 6 months postoperatively. The BCVA was compared before and after PPV between the two groups, and postoperative complications of revitrectomy PPV group were analyzed. Quantitative data are presented as medians [ M ( Q 1 , Q 3 )]. Results: The age of single PPV group patients was 55.0 (47.0, 63.0), and the age of revitrectomy PPV group patients was 49.0 (38.0, 57.0). This difference was statistically significant ( P =0.027). The LogMAR visual acuity of two groups were 1.7 (1.0, 2.4) and 2.1 (1.4, 2.4) ( P =0.026) preoperative; the visual acuity of single PPV group was 0.75 (0.43, 1.00) ( P <0.001), and revitrectomy PPV group was 0.95 (0.60, 1.65) ( P <0.001) at 6 months postoperative. The visual acuity improvement of single PPV group was better than revitrectomy PPV group ( P =0.021). Age ( P =0.043, OR =0.97, 95% CI : 0.95-1.00), preoperative BCVA ( P =0.024, OR =1.82, 95% CI : 1.08-3.05), tractional retinal detachment (TRD) ( P =0.033, OR =2.16, 95% CI :1.06-4.37), silicone oil tamponade ( P =0.028, OR =0.48, 95% CI : 0.25-0.92) were prognostic factors of revitrectomy. Conclusion: Young age, low preoperative BCVA, TRD, and silicon oil tamponade were the potential prognostic factors of revitrectomy for PDR patients.

Objective: To explore the feasibility and clinical efficacy of a modified medial collateral ligament indentation technique in total knee arthroplasty (TKA) with severe type II valgus deformity., Methods: Consecutive patients with Krackow type II valgus deformity >20° who underwent a primary unilateral TKA between May 2008 and June 2017 were studied retrospectively. A medial collateral ligament indentation technique was performed in 20 patients (MCLI group), and 23 patients received the routine lateral structures release technique (LSR group). Radiological parameters, such as the valgus angle (VA), and functional outcomes including the use of constraint implants, Knee Society Score (KSS), Knee Society Function score (KSF), and thickness of the polyethylene insert were compared between the two groups., Results: A total of 43 consecutive patients had a minimum 2-year follow-up. The preoperative VA was comparable between the MCLI (23.5° ± 5.8°) and LSR groups (21.3° ± 3.2°, P = 0.134), as was the postoperative VA (1.1° ± 2.1° and 2.5° ± 3.0°, respectively, P = 0.084). The mean KSS and KSF scores in the MCLI group were 30.2 ± 4.8 and 38.8 ± 4.8, respectively, before surgery, and they increased to 91.3 ± 2.6 and 86.5 ± 2.4 at the last follow-up. The scores in the LSR group were 31.5 ± 7.5 and 36.5 ± 7.8 before surgery and 92.4 ± 3.5 and 88.5 ± 3.6 at the last follow-up. While no statistically significant differences in pre- or postoperative functional scores were found between the two groups, the MCLI group had thinner polyethylene inserts (9.5 ± 1.1 mm vs 12.9 ± 1.5 mm) and less use of constrained condylar inserts (15% vs 69.6%). During follow-up, the MCLI group had fewer complications., Conclusion: A modified MCLI technique can achieve good outcomes in TKA with type II valgus deformity of >20°. It can maintain a normal joint line level, reduce the use of constrained condylar knee prostheses, and is a reliable choice for severe genu valgum., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Ganoderma lucidum is a white-rot fungus that produces a range of lignocellulolytic enzymes to decompose lignin and cellulose. The mitogen-activated protein kinase (MAPK) pathway has been implicated in xylanases and cellulases production. As the downstream transcription factor of Slt2-MAPK, the function of Swi6 in G. lucidum has not been fully studied. In this study, the transcription factor GlSwi6 in G. lucidum was characterized and shown to significantly positively regulate cellulases and xylanases production. Knockdown of the GlSwi6 gene decreased the activities of cellulases and xylanases by approximately 31%~38% and 54%~60% compared with those of the wild-type (WT) strain, respectively. Besides, GlSwi6 can be alternatively spliced into two isoforms, GlSwi6A and GlSwi6B, and overexpression of GlSwi6B increased the activities of cellulase and xylanase by approximately 50% and 60%, respectively. Further study indicates that the existence of GlSwi6B significantly increased the concentration of cytosolic Ca 2+ . Our study indicated that GlSwi6 promotes the activities of cellulase and xylanase by regulating the Ca 2+ signaling. These results connected the GlSwi6 and Ca 2+ signaling in the regulation of cellulose degradation, and provide an insight for further improvement of cellulase or xylanase activities in G. lucidum as well as other fungi.

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure. Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study. Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline. Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335-35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen ( P = 0.162), were predictors of the treatment duration. Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Long, Hou, Miao and Zhao.)

Objective: To study the macular choroidal volume (MCV) of patients with highly myopic foveoschisis and its clinical value. Methods: In this cross-sectional study, 39 outpatients (39 eyes) with highly myopic foveoschisis were included from January 2016 to December 2020 in Peking University People's Hospital, including 18 males and 21 females. Their age was (59.3±6.7) years old. Thirty-nine highly myopic patients (39 eyes) with no macular complications were enrolled as control group. The age, gender, and refractive error were matched between two groups. Medical history information and eye examination information including refractive error, axial length and best corrected visual acuity were recorded. All patients had undergone high-resolution enhanced depth imaging optical coherence tomography to measure the retinal and choroidal thickness of multiple parts of the macular zone. According to the image characteristics, myopic foveoschisis patients were divided into the inner and outer myopic foveoschisis subgroups, and the MCV characteristics were analyzed. The independent sample t test, Pearson correlation analysis and linear regression analysis were used. Results: The subfoveal choroidal thickness was (74.9±59.3) and (155.6±47.1) μm, and MCV was (2.3±0.8) and (5.3±1.0) mm 3 in the foveoschisis group and the control group, respectively. The differences were statistically significant ( t =-6.649, -15.229; P <0.01). Although no correlation was found between subfoveal choroidal thickness and central foveal thickness in both groups ( r =0.103, 0.214; P >0.05), MCV was negatively correlated with macular retinal volume (MRV) in the foveoschisis group ( y =-2.90 x +18.48; r 2 =0.47, P = 0.01). In the control group, there was a positive correlation between MCV and MRV ( y =0.74 x +2.02; r 2 =0.64, P =0.01). The best corrected visual acuity was positively associated with MCV in patients with foveoschisis ( r =0.677, P <0.05). The MCV of inner (19 eyes) and outer (15 eyes) foveoschisis subgroups was (2.80±0.81) and (1.92±0.27) mm 3 , and the difference was statistically significant ( t =4.610, P <0.05). Conclusions: The MCV significantly decreased in patients with highly myopic foveoschisis. The smaller the MCV, the scarcer the blood supply of the outer retina, the more serious the foveoschisis, and the larger the MRV. (Chin J Ophthalmol, 2021, 57:419-425) .

Purpose: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months., Methods: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12., Results: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 μm at baseline to 308.73 ± 106.80 μm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm 3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm 3 at baseline to 0.48 ± 0.71 mm 3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm 3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81., Conclusion: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

Aim: To evaluate the two-year outcomes of patients treated for diabetic macular edema (DME) with intravitreal Conbercept (IVC)., Methods: The clinical data of 30 DME patients (36 eyes) were retrospectively reviewed. The patients were treated with IVC for 3mo. Additional IVC was given at subsequent monthly visits, if needed (3+PRN). The patients were followed up for 24mo., Results: The best-corrected visual acuity (BCVA) at 24mo significantly increased (66.7±15.3 letters) in comparison with the baseline (54.4±15.4 letters, P <0.0001). The mean improvement in BCVA was 11.0±2.9 letters. At 24mo, 44.1% of the eyes surveyed gained ≥15 letters, 52.9% of the eyes gained ≥10 letters, and 70.6% of the eyes gained ≥5 letters. No vision loss was noted in 96.8% of the eyes, and 5.9% of the eyes lost ≥5 letters, but ≤10 letters. The central retinal thickness (CRT) at 24mo was significantly reduced (277.1±122.9 µm) in comparison with the baseline (510.9±186.1 µm, P <0.0001). At 24mo, 43.3% of the patients had a CRT ≤250 µm. The mean number of injections over 24mo was 10.6±2.0. No severe eye or systemic adverse events related to either the drug or injection were noted., Conclusion: IVC is safe and effective for the treatment of DME., (International Journal of Ophthalmology Press.)

Purpose: To compare capillaries perfusion in macular areas at different layers and peripapillary region in radial peripapillary capillaries (RPC) between healthy subjects and subjects with obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA)., Methods: Totally 16 eyes with mild-to-moderate OSA, 14 eyes with severe OSA and 22 control eyes were enrolled in this study. Every subject filled out the Berlin questionnaire and received a comprehensive ocular and physical examination. The clinical characteristics were collected, OCT and OCTA scans using OCTA RT XR Avanti (AngioVue software, Optovue Inc., Fremont, CA, USA) were performed and analyzed., Results: Compared to the control group, the severe group had significantly higher VD in parafovea and perifoveal regions (p = 0.031; p = 0.029) at the level of deep capillary plexus (DCP), whereas the mild-to-moderate group had a significantly lower VD in the peripapillary region on RPC network in disc areas (p = 0.013)., Conclusions: Blood flow changes in macular areas might first appear at the DCP layer in OSA patients. Reduced VD in the peripapillary region at the RPC layer might be associated with OSA and cause subsequent RNFL changes.

Background: Epilepsy is a one of the most frequent serious neurological disorders characterized by enduring and unprovoked seizures. The treatments to epilepsy are very limited and many patients are even resistant to current medications due to the elusive pathogenesis. Here, we sought to investigate the functions of lncRNA SNHG1 and miR-154-5p in epilepsy., Methods: We employed both in vivo mouse model and in vitro cell model to study epilepsy. H&E staining and Nissl staining were used to examine the morphology of hippocampus and measure neuronal injury, respectively. TUNEL staining and flow cytometry were performed to determine cell apoptosis. Caspase-3 activity assay kit was used to assess caspase-3 activity. RT-qPCR and western blot were conducted to measure the levels of SNHG1, miR-154-5p, TLR5, and SP1, respectively. Dual luciferase reporter assay was employed to validate the binding relationship of SNHG1/miR-154-5p and miR-154-5p/TLR5. ChIP assay was performed to confirm the transcriptional regulation of SP1 on SNHG1., Results: Elevated SNHG1 and decreased miR-154-5p were observed in both in vivo mouse model and in vitro cell model of epilepsy. Knockdown of SNHG1 or transfection with miR-154-5p mimics significantly ameliorated Mg 2+ free-induced neuronal injury in SH-SY5Y cells. SNHG1 acted as a sponge of miR-154-5p. Moreover, SNHG1 promoted neuronal injury via acting as a miR-154-5p sponge to disinhibit TLR5. Additionally, SP1 activated the transcriptional activity of SNHG1., Conclusion: In summary, SP1 transcriptionally activated-SNHG1 contributes to the development of epilepsy via directly regulating miR-154-5p/TLR5 axis, which provides novel targets in treatment of epilepsy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

When fungi are subjected to abiotic stresses, the polyamines (PAs) level alter significantly. Here, we reveal that the polyamine putrescine (Put) could play an important role in alleviating heat stress(HS)-induced accumulation of nitric oxide (NO). Ornithine decarboxylase (ODC)-silenced mutants that were defective in Put biosynthesis exhibited significantly lower NO levels than the wild type (WT) when subjected to HS. With addition of 5 mM exogenous Put, the ODC-silenced mutant endogenous Put obviously increased under HS. At the same time, the contents of NO in the ODC-silenced mutants recovered to approximately WT levels after the administration of exogenous Put. However, the elevated NO content in the ODC-silenced mutants disappeared when exogenous Put and carboxy-PTIO (PTIO is a specific scavenger of NO) were added. Intriguingly, the content of glutamine (Gln) was significantly increased in the ODC-silenced strains. When exogenous Put was added to the WT, the Gln content was significantly decreased. The appearance of a high level of Gln was accompanied by nitrate reductase (NR) activity reduction. Further studies showed that Put influenced ganoderic acids (GAs) biosynthesis by regulating NO content, possibly through NR, under HS. Our work reported that Put regulates HS-induced NO accumulation by changing the cellular Gln level in filamentous fungi. IMPORTANCE: In our present work, it was HS as an ubiquitous environmental stress that affects the important pharmacological secondary metabolite (GAs) content in G. lucidum. Afterwards, we began to explore the network formed between multiple substances to jointly reduce the massive accumulation of GAs content caused by HS. We firstly focused on Put, a substance that enhances resistance to multiple stresses. Further, we discovered an influence on Put could changing the NO content, which has been shown to decrease the accumulation of GAs via HS. Then, we also found the change of NO content may be due to Put level that would affect intracellular Gln content. It has never been reported. And ultimately, it is Put related network that could reduce HS-inducing secondary metabolite mess in fungi., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objective: To evaluate the potential association between optic nerve invasion and optic nerve obscuration during treatment of advanced retinoblastoma. Methods: Retrospective case series study. Medical records of 77 patients (77 eyes) with advanced retinoblastoma (Group D/E) who were treated with primary or secondary enucleation in the Ophthalmology Department of Peking University People's Hospital from January 1 st 2012 to December 31 th 2015 were retrospectively reviewed. RetCam photographs under general anesthesia at diagnosis and each subsequent follow-up were evaluated for complete obscuration of the optic nerve. The primary endpoints included prelaminar invasion, postlaminar invasion and optic nerve transection invasion. Group difference was calculated with chi-square. Results: There were 46 boys and 31 girls in the study. The mean age at the first diagnosis was (27.1±22.1) months. The optic nerve was obscured in 62 eyes (80.5%) at the first diagnosis and 61 eyes (79.2%) at the last ocular examination prior to enucleation. Twenty-nine eyes (37.7%) underwent primary enucleation. Forty-eight eyes (62.3%) were treated with eye-preserving therapy, followed by enucleation. Fourteen eyes (18.2%) were in Group D and 63 eyes (81.8%) were in Group E. Histopathologic analysis of enucleated eyes without optic nerve obscuration (16 eyes) showed prelaminar invasion in 7 eyes, postlaminar invasion in 2 eyes and optic nerve transection invasion in 0 eyes. Histopathologic analysis of enucleated eyes with optic nerve obscuration (61 eyes) showed prelaminar invasion in 26 eyes, postlaminar invasion in 9 eyes and optic nerve transection invasion in 4 eyes. The difference between two groups did not achieve statistical significance ( P =0.935, 1.000, 0.296). Histopathologic analysis of enucleated eyes with persistent complete obscuration of the optic nerve showed a high risk factor in 10 eyes (10/40), while in 1 eye (1/8) the optic nerve was visible at the initial presentation and obscured before secondary enucleation ( P =0.529). Conclusion: Optic nerve obscuration at the last examination prior to enucleation may not be associated with postlaminar optic nerve invasion in advanced retinoblastoma. (Chin J Ophthalmol, 2020, 56: 681-687) .

Retinal vein occlusion (RVO) is the consequence of obstruction of retinal vein system caused by a variety of etiologies. Its ocular complications include macular edema, retinal ischemia and neovascular glaucoma. Although many drugs for management of RVO are available, some doctors do not fully understand the exact purpose of each treatment. This article starts from the etiology evaluation of RVO, emphasizing that, besides systemic etiology and risk factor management, the treatment of RVO should focus on the three major complications at the same time, rather than just dealing with macular edema. Meanwhile, a regular follow-up for observing the changes of the degree of retinal ischemia is important for whole course management. Anti-vascular endothelial growth factor therapy, the first-line treatment option of RVO, can not only reduce macular edema, but also prevent the complications caused by retinal ischemia and create opportunities for further laser photocoagulation. Laser photocoagulation has an irreplaceable value in the comprehensive treatment of ischemic RVO. Glucocorticoid intraocular implants should not be used alone in the treatment of macular edema secondary to RVO. (Chin J Ophthalmol, 2020, 56:246-249) .

Although many advances have been made in the pathogenesis of epilepsy recently, the pathological mechanisms of epilepsy are still largely unknown. Exploring the pathological mechanisms and developing novel therapeutic strategies for epilepsy are urgently needed. A SD rat model of epilepsy was established with lithium chloride-pilocarpine. Astrocytes were isolated, cultured from 8 to 12 week rats and identified by flow cytometry and immunofluorescence. Immunohistochemical staining was used for MEF2C and NF-κB in paraffin-embedded sections. RT-qPCR and western blot were used to analyze gene expression. ELISA was used to analyze the concentration of IL-6, TNF-α and Cox-2. Cells were transfected with pcDNA-MEFC2, sh-MEFC2, pcDNA-UCA1, sh-UCA1, miR-203 mimic or miR-203 inhibitor. Cell viability was assessed by MTT assay. Dual luciferase assay was used to determine the direct interaction of lncRNA UCA1/miR-203 and miR-203/MEF2C. MEF2C was down-regulated and inhibited NF-κB expression and the secretion of IL-6 and TNF-α in epilepsy. LncRNA UCA1 was also down-regulated in epilepsy. LncRNA UCA1 over-expression increased the expression of MEF2C and its knock-down decreased MEF2C expression. Luciferase activity showed lncRNA UCA1 directly targeted miR-203 and miR-203 directly targeted MEF2C. MiR-203 suppressed the expression of MEF2C, and promoted NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was reversed by MEF2C knock-down. Moreover, lncRNA UCA1 could increase the expression of MEF2C to inhibit NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was also reversed by miR-203 mimic transfection. LncRNA UCA1 inhibited the inflammation via regulating miR-203 mediated regulation of MEF2C/NF-κB signaling in epilepsy. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for epilepsy.

The AMP-activated protein kinase (AMPK)/Sucrose-nonfermenting serine-threonine protein kinase 1 (Snf1) plays an important role in metabolic remodelling in response to energy stress. However, the role of AMPK/Snf1 in responding to other environmental stresses and metabolic remodelling in microorganisms was unclear. Heat stress (HS), which is one important environmental factor, could induce the production of reactive oxygen species and the accumulation of ganoderic acids (GAs) in Ganoderma lucidum. Here, the functions of AMPK/Snf1 were analysed under HS condition in G. lucidum. We observed that Glsnf1 was rapidly and strongly activated when G. lucidum was exposed to HS. HS significantly increased intracellular H 2 O 2 levels (by approximately 1.6-fold) and decreased the dry weight of G. lucidum (by approximately 45.6%). The exogenous addition of N-acetyl-l-cysteine (NAC) and ascorbic acid (VC), which function as ROS scavengers, partially inhibited the HS-mediated reduction in biomass. Adding the AMPK/Snf1 inhibitor compound C (20 μM) under HS conditions increased the H 2 O 2 content (by approximately 2.3-fold of that found in the strain without HS treatment and 1.5-fold of that found in the strain under HS treatment without compound C) and decreased the dry weight of G. lucidum (an approximately 28.5% decrease compared with that of the strain under HS conditions without compound C). Similar results were obtained by silencing the Glsnf1 gene. Further study found that Glsnf1 meditated metabolite distribution from respiration to glycolysis, which is considered a protective mechanism against oxidative stress. In addition, Glsnf1 negatively regulated the biosynthesis of GA by removing ROS. In conclusion, our results suggest that Glsnf1-mediated metabolic remodelling is involved in heat stress adaptability and the biosynthesis of secondary metabolites in G. lucidum., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Verticillium wilt, an infection caused by the soilborne fungus Verticillium dahliae, is one of the most serious diseases in cotton. No effective control method against V. dahliae has been established, and the infection mechanism of V. dahliae in upland cotton remains unknown. GFP-tagged V. dahliae isolates with different pathogenic abilities were used to analyse the colonisation and infection of V. dahliae in the roots and leaves of different upland cotton cultivars, the relationships among infection processes, the immune responses and the resistance ability of different cultivars against V. dahliae. Here, we report a new infection model for V. dahliae in upland cotton plants. V. dahliae can colonise and infect any organ of upland cotton plants and then spread to the entire plant from the infected organ through the surface and interior of the organ. Vascular tissue was found to not be the sole transmission route of V. dahliae in cotton plants. In addition, the rate of infection of a V. dahliae isolate with strong pathogenicity was notably faster than that of an isolate with weak pathogenicity. The resistance of upland cotton to Verticillium wilt was related to the degree of the immune response induced in plants infected with V. dahliae. These results provide a theoretical basis for studying the mechanism underlying the interaction between V. dahliae and upland cotton. These results provide a theoretical basis for studying the mechanism underlying the interaction between V. dahliae and upland cotton., (© 2019 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

The transcription factor PacC/Rim101 participates in environmental pH adaptation, development and secondary metabolism in many fungi, but whether PacC/Rim101 contributes to fungal adaptation to environmental stress remains unclear. In our previous study, a homologous gene of PacC/Rim101 was identified, and PacC-silenced strains of the agaricomycete Ganoderma lucidum were constructed. In this study, we further investigated the functions of PacC in G. lucidum and found that PacC-silenced strains were hypersensitive to environmental stresses, such as osmotic stress, oxidative stress and cell wall stress, compared with wild-type (WT) and empty-vector control (CK) strains. In addition, transmission electron microscopy images of the cell wall structure showed that the cell walls of the PacC-silenced strains were thinner (by approximately 25-30%) than those of the WT and CK strains. Further analysis of cell wall composition showed that the β-1,3-glucan content in the PacC-silenced strains was only approximately 78-80% of that in the WT strain, and the changes in β-1,3-glucan content were consistent with downregulation of glucan synthase gene expression. The ability of PacC to bind to the promoters of glucan synthase-encoding genes confirms that PacC transcriptionally regulates these genes., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objective: To study the effects of human umbilical mesenchymal stem cells (HUMSCs) exosomes on the proliferation and apoptotic as well as migration of human retinal pigment epithelial cells (HRPE) in hypoxia, and explore its mechanism. Method: Direct adherent culture was adopted to cultivate umbilical cord mesenchymal stem cells and amplified to the fourth generation. Markers on the cell surface were identified by flow cytometry. Culture medium was collect without serum from the 4th generation umbilical cord mesenchymal stem cells. Exosomes were separated and extracted, then the ultrastructure was observed under electron microscope and examined expression of CD63 and CD9 protein by Western blot method with isolated and extracted exosomes. HRPE was cultivated in vitro culture, proliferation was detected at the time point of 0, 1, 2, 3, 4, 5 d with MTT assay under hypoxic condition. Meanwhile, the cell migration was quantified by Wound-Healing Assay under hypoxic condition at 0, 24, 48 and 72 h respectively combined with apoptosis test. The HRPE cells in the growth period were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 μg/ml). In all groups, apoptosis was observed by Annexin V/PI dual-dye flow cytometry after 48 h's incubation. Proliferation was observed by MTT assay and the migration was observed with Wound-Healing Assay. Results: Flow cytometry detection of the surface marker of HUMSCs in the 4th generation showed strong positive expression of CD105, CD73, CD90. It was suggested that HUMSCs with isolated culture had MSC specific phenotype with duction of lipids and osteoblasts in vitro. The separated exosomes were observed with spherical membranous structures in different sizes by scanning electron microscopy, and Western blot detected positive expression of CD63 and CD9. In vitro culture of HRPE detected by MTT assay for cell proliferation at the time of hypoxic 0, 1, 2, 3, 4, 5 d, the results showed that, comparing with time point 0 d, other groups had statistically significant OD values. In the first 2 days, the proliferation ability of RPE cells gradually increased as the time of hypoxia prolonged(1.862±0.135, 2.278±0.244). After 3 d, the proliferation ability of RPE cells gradually decreased(1.419±0.124, 1.599±0.156). Wound-Healing Assay results showed that the migration distance gradually increased as[(29.883±4.504), (36.200±1.928) μm] the time of hypoxia increased from 0 to 72 h. The cells were fully covering at the point of 72 h [(1.223±0.194), (0.430±0.299) μm]. Apoptosis test results showed that the number of apoptotic cells was different(3.628%±1.348%, 20.123%±1.183%) with the extension of hypoxia Oxygen before 2 d from 0 to 72 h. At the time of d3, there were more apoptotic cells(42.290%±3.217%). There is a significant difference from pre-2d.RPE cells were divided into 5 groups: the control group, the hypoxia group and the pretreated exosomes group (100, 200, 300 μg/ml).After 48 h hypoxia incubation, MTT assay results showed that, compared with the control group (1.870±0.499), the number of cell proliferation was significantly increased ( t= -3.116, P< 0.05), while compared with the hypoxia group(2.616±0.307), the proliferation number of exosomes was significantly reduced [(2.041±0.115), (1.931±0.205), (1.929±0.025); t =-4.920, -4.540, -5.286, P< 0.01], and there was no significant difference between groups with different doses of the exosomes ( F= 1.181, P> 0.05). Annexin V/PI dual-dye flow cytometry was used to observe the apoptosis results. Compared with the control group 1.180%±0.689%, the number of apoptosis in hypoxia group was significantly increased (19.273%±1.194%, t= -32.141, P< 0.01), while compared with the hypoxia group, the number of apoptosis in the exosomes was significantly decreased (12.318%±1.087%, 11.878%±1.348%, 11.090%±1.716%; t =-10.547, -10.057, 9.589, P< 0.01). There was no significant difference between the groups with different doses of exosomes ( F= 1.173, P> 0.05). Wound-Healing Assay results showed that, compared with the control group(68.047±2.851) μm, the migration distance of the hypoxia group was significantly increased [(13.470±2.255)μm, t= 36.778, P< 0.01] while compared with the hypoxia group, the migration distance of the exosomes was reduced (33.110±1.774, 24.650±1.175, 26.440±1.674; t =11.766, 10.770, 11.311, P< 0.01), and there was no significant difference between the groups of the exosomes ( F= 1.179, P> 0.05). Conclusion: Human umbilical cord mesenchymal stem cells can effectively inhibit the apoptosis and migration of HRPE cells in hypoxia. It provides a theoretical basis for the research and treatment of RPE related diseases. (Chin J Ophthalmol, 2019, 55: 933-941) .

Ganoderma lucidum is widely recognized as a medicinal basidiomycete. It was previously reported that the plant hormone methyl jasmonate (MeJA) could induce the biosynthesis of ganoderic acids (GAs), which are the main active ingredients of G. lucidum . However, the regulatory mechanism is still unclear. In this study, integrated proteomics and metabolomics were employed on G. lucidum to globally identify differences in proteins and metabolites under MeJA treatment for 15 min (M15) and 24 h (M24). Our study successfully identified 209 differential abundance proteins (DAPs) in M15 and 202 DAPs in M24. We also identified 154 metabolites by GC-MS and 70 metabolites by LC-MS in M24 that are involved in several metabolic pathways. With an in-depth analysis, we found some DAPs and metabolites that are involved in the oxidoreduction process, secondary metabolism, energy metabolism, transcriptional and translational regulation, and protein synthesis. In particular, our results reveal that MeJA treatment leads to metabolic rearrangement that inhibited the normal glucose metabolism, energy supply, and protein synthesis of cells but promoted secondary metabolites, including GAs. In conclusion, our proteomics and metabolomics data further confirm the promoting effect of MeJA on the biosynthesis of GAs in G. lucidum and will provide a valuable resource for further investigation of the molecular mechanisms of MeJA signal response and GA biosynthesis in G. lucidum and other related species.

Hydrogen sulfide (H 2 S), an emerging small-molecule signalling agent, was recently shown to play a significant role in many physiological processes, but relatively few studies have been conducted on microorganisms compared with mammals and plants. By studying the pretreatment of H 2 S donor sodium hydrosulfide (NaHS) and the scavenger hypotaurine (HT) and Cystathionine β-synthase silenced strains, we found that H 2 S could alleviate the HS-induced ganoderic acids (GAs) biosynthesis. Our transcriptome results also showed that many signaling pathways and metabolic pathways, such as the glycolysis, TCA, oxidative phosphorylation and pentose phosphate pathway, are influenced by H 2 S. Further experimental results indicated that H 2 S could affect the physiological process of Ganoderma lucidum by interacting with multiple signals, including ROS, NO, AMPK, sphingolipid, mTOR, phospholipase D and MAPK, and physiological and pharmacological analyses showed that H 2 S might alleviate the biosynthesis of GAs by inhibiting the intracellular calcium in G. lucidum., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetic retinopathy (DR) is one of the most important etiologies of diabetic blindness. The vascular endothelial growth factor (VEGF) is thought to mediate pathophysiological changes of DR. Anti-VEGF therapy for DRdevelops rapidly. However, there are some misunderstandings about its clinical application, and the strategy is not clear. Sometimes its therapeutic effects are even exaggerated. In this article, by discussing whether anti-VEGF therapy can reverse the course of DR disease, promote the absorption of vitreous hemorrhage, and replace fundus laser therapy, the application strategy of anti-VEGF therapy for DR is proposed. At present, anti-VEGF therapy cannot completely replace retinal photocoagulation therapy, and its clinical application value should not be exaggerated. More innovative drugs and therapies are expected to provide new ways forthe treatment of DR while preserving visual function. (Chin J Ophthalmol, 2019, 55: 565-568) .

Aim: To explore the process of retinal vascularization and risk factors for retinopathy of prematurity (ROP) treated with intravitreal ranibizumab (IVR) as monotherapy., Methods: Infants with type 1 ROP who received IVR as primary treatment from August 2014 to October 2016 at Peking University People's Hospital's Ophthalmology Department were included in the study. All eyes received 0.25 mg ranibizumab at initial treatment. Retinal vascularization was evaluated clinically. Potential risk factors were also recorded and examined., Results: Retinal vascularization was completed in 126 eyes (62.7%), and retinal vascularization terminated in zone II and zone III with 16 eyes (7.9%) and 44 eyes (21.9%), respectively, after more than 1-year follow-up. In multivariate regression analysis, lower birth weight (BW), severity of ROP and repeated injections were found to be risk factors for peripheral avascular area ( P <0.05)., Conclusion: In our retrospective study, 29.8% of the ROP eyes treated with ranibizumab have peripheral avascular area at the last follow-up. Lighter BW and the severity of ROP are risk factors. Furthermore, repeated injections also increase the risk of retinal peripheral avascular area remaining in ROP patients.

Background: The insecticide exposure has been linked to Parkinson's disease (PD). In the present study, we used a most widely used cell line in study of PD, the SH-SY5Y cells, to investigate mechanisms of chlorpyrifos (CPF) induced cell toxicity and the possible roles of cell pyroptosis and oxidative stress in SH-SY5Y cells, as well as role of miR-181/SIRT1/PGC-1α/Nrf2 signaling pathway in this process., Methods: SH-SY5Y cells were treated with different concentrations of CPF. Cell viability was measured using CCK-8 assay. Cell pyroptosis was determined by immunofluorescence of caspase-1 and TUNEL assay. The miR-181 (has-miR-181-5p) level was determined by qRT-PCR. Expression of SIRT1, PGC-1α, Nrf2, and pyroptosis related proteins NLRP3, caspase-1, IL-1β, and IL-18 was determined by both qRT-PCR and Western blotting., Results: Cell viability was found to be decreased with the increased CPF concentrations. The pyroptosis related proteins, ROS levels, as well as level of caspase-1 and the TUNEL positive cells were all significantly up-regulated by CPF. Meanwhile, expression of miR-181 and pyroptosis proteins was also enhanced, while the SIRT1/PGC-1α/Nrf2 signaling was inhibited by CPF. Knockdown of Nrf2 significantly up-regulated the expression of pyroptosis related proteins, ROS level, caspase-1, and the TUNEL positive cells, while over-expression of Nrf2 resulted in opposite results. The expression of PGC-1α and Nrf2 was significantly down-regulated when SIRT1 was inhibited, while over-expressed SIRT1 led to increased PGC-1α and Nrf2 levels. Besides, miR-181 promoted the CPF induced activation of pyroptosis and oxidative stress, as well as down-regulated SIRT1/PGC-1α/Nrf2 signaling, while inhibition of miR-181 led to opposite results., Conclusions: Chlorpyrifos could inhibit cell proliferation, activate cell pyroptosis and increase susceptibility on oxidative stress-induced toxicity by elevating miR-181 through down-regulation of the SIRT1/PGC-1α/Nrf2 pathway in human neuroblastoma SH-SY5Y cells. This study might give deeper insights for mechanisms of CPF induced toxicity and might give some novel research targets for PD treatment., (© 2019 Wiley Periodicals, Inc.)

The fungal cell wall is very important for cell growth and survival during stress, and the target of rapamycin (TOR) pathway plays a major role in regulating cell growth in response to environmental cues. Ganoderma lucidum is an important edible and medicinal fungus, and the function of TOR in this organism remains unclear. As shown in the present study, the TOR pathway regulates cell wall integrity (CWI) in G. lucidum. Inhibition of TOR signaling by RNA interference (RNAi) or rapamycin treatment reduced the growth of G. lucidum mycelia, increased contents of the cell wall components chitin and β-1,3-glucan, and increased cell wall thickness. Furthermore, inhibition of TOR signaling enhanced the relative level of phosphorylated Slt2, a member of the MAPK cascade involved in CWI signaling. Moreover, when treated with rapamycin, significantly lower chitin and β-1,3-glucan contents were observed in Slt2-silenced strains than in WT strains, indicating that TOR regulates the synthesis of these cell wall components through the Slt2-MAPK pathway. These results indicate a potential relationship between TOR signaling and CWI signaling. Additionally, participation of Slt2-MAPK in TOR-mediated regulation of cell wall component production has not previously been reported in a microorganism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: To describe the involution patterns of vessel growth of retina through fluorescein angiography (FA) of children, who had been under treatment up to 1y previously intravitreal ranibizumab (IVR) as monotherapy for retinopathy of prematurity (ROP)., Methods: This is a retrospective study. The medical information and FA of 17 children (34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters (DD) were analyzed., Results: Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts (100%, 34/34 eyes). Popcorn abnormalities were found in most of the eyes (94.1%, 32/34 eyes). Furthermore, in many cases (23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes (5.9%) showed damage of retinal capillary bed and 3 eyes (8.8%) showed large area of retinal pigment epithelium (RPE) atrophy., Conclusion: Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.

Aim: To evaluate the real-life clinical outcomes of intravitreal injection of conbercept combined rescue therapy for polypoidal choroidal vasculopathy (PCV)., Methods: This was an open label, single center, and interventional study. All enrolled patients were treated initially with three consecutive monthly intravitreal conbercept injections (0.5 mg). Additional conbercept injections were administered upon substantial polyp regression with improved visual acuity (VA). Eyes with partial or no polyp regression and poor VA were rescue treated with photodynamic therapy (PDT) for subfoveal polyps or thermal laser photocoagulation for extrafoveal polyps. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and polyp regression were observed as primary outcomes. Side effects were also collected during the follow-up period., Results: A total of 56 eyes (56 patients) with PCV were included. BCVA increased significantly from the baseline of 43.52±24.21 letters to 55.88±21.94 letters ( P <0.001) at 12mo, while CFT decreased significantly from 457.41±207.86 µm to 247.98±127.08 µm ( P <0.001). All patients showed polyp regression. Twenty-three eyes achieved complete polyp regression after the three initial injections, which increased to 44 eyes at 12mo. Seventeen eyes underwent rescue therapy, among which 2 eyes treated with PDT and 15 eyes treated with laser photocoagulation. A mean of 4.30±1.43 injections were given per eye. No intraocular inflammation, retinal or vitreous hemorrhage, or systemic complication occurred., Conclusion: Conbercept is an effective and safe option for the treatment of PCV in Chinese population. The treatment regimen of three initial conbercept injections followed by additional injections or rescue therapies is efficacious for treating PCV.