Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Reconfigurable reflective multifunction OAM metasurface based on spin-decoupling.

This Letter develops a spin-decoupled reconfigurable reflective orbital angular momentum (OAM) metasurface (MTS). The reconfigurability is realized by switching the feed among left-hand circular polarization (LHCP), right-hand circular polarization (RHCP), and linear polarization (LP) incidences, and the reconfigurable design principle is provided. This Letter also proposes a design method for the desired energy ratio between the co-polarized and cross-polarized beams. Compared with published multifunction MTSs, the designed MTSs have the following advantages: multi-polarizations, arbitrary beam numbers and modes, composite waveform (pencil and OAM beams), high aperture efficiency (21.1%, 14.6%, 6.63% for RHCP, LP, and LHCP incidences, respectively), high purity (above 92.41%), required energy distribution ratio, and reconfigurability. The MTSs have potential prospects in high-capacity wireless communications.

Microbial spectrum and risk factors of endogenous endophthalmitis in a tertiary center of Northern China.

AIM: To study the clinical features, microbial spectrum, associated factors and prognosis of endogenous endophthalmitis (EE) in a group of Chinese patients. METHODS: The medical records from 32 eyes of 29 patients diagnosed with EE in Peking Union Medical College Hospital from January 2009 to October 2019 were reviewed. RESULTS: The initial visual acuity (VA) of 30 eyes in this study was worse than 20/400. Twenty-three eyes were diagnosed with fungal endophthalmitis and nine with bacterial endophthalmitis. The most common fungal and bacterial isolates were Candida and Klebsiella pneumoniae, respectively. Several rare fungi and bacteria species were also isolated from our patients, including Cryptococcus, Paecilomyces, Brucella, and Bacillus licheniformis. The leading risk factor for EE was diabetes. The most common extraocular infection locus was genitourinary tract. Vitrectomy was performed on twenty-nine eyes. Eight eyes achieved final VA of 20/400 or better. EE caused by Candida had a better prognosis. CONCLUSION: The visual outcome of EE is based on pathogens and prompt intervention. Early vitrectomy and antimicrobial treatment are beneficial for EE.

Clinical features and treatment outcomes of intraocular lymphoma: a single-center experience in China.

AIM: To investigate the clinical manifestations, diagnostic approaches, treatments, and outcomes of intraocular lymphoma. METHODS: In this retrospective study, 16 patients (28 eyes) with intraocular lymphoma were recruited in the Department of Ophthalmology, Peking Union Medical College Hospital, from 2004 to 2019. All patients underwent comprehensive ophthalmic examinations. Vitreous specimens of 13 patients were sent for cytopathology examination and other adjunctive diagnostic procedures. Three patients were diagnosed with intraocular lymphoma according to analysis of the histopathological results of systemic lymphoma by one clinician. Twenty-three eyes were treated with intravitreal administration of methotrexate, 4 eyes could not receive ocular treatment due to life-threatening lymphoma, and 1 eye did not require ocular treatment because the fundus lesions regressed after systematic chemotherapy. RESULTS: In 28 eyes, 25 eyes were diagnosed with vitreoretinal lymphoma, and 3 eyes were diagnosed with ciliary body lymphoma, all of which were non-Hodgkin diffuse large B cell lymphomas. The final visual acuity improved in 15 eyes (54%), remained unchanged in 5 eyes (18%), and decreased in 8 eyes (29%). Anterior segment inflammation disappeared or reduced in 8 and 5 eyes, respectively; and 15 eyes had no anterior segment reaction. Twenty eyes had mild vitreous opacity, 1 eye had mild vitritis, and 7 eyes had pars plana vitrectomy combined with silicone oil tamponade. Fundus lesions disappeared in 9 eyes and were relieved in 5 eyes; 4 eyes showed no changes, and the remaining 10 eyes' fundus were normal. CONCLUSION: The clinical manifestations of intraocular lymphoma are diverse, and the misdiagnosis rate is high. Cytopathological analysis of vitreous is one of the gold standards for the diagnosis. Immunohistochemistry, gene rearrangement and flow cytometric immunophenotypic analysis can improve the diagnostic rate. Ocular chemotherapy or radiotherapy regimens may preserve visual acuity, and a multidisciplinary team can provide individualized treatment for the patients.

A promising approach for screening pulmonary hypertension based on frontal chest radiographs using deep learning: A retrospective study.

BACKGROUND: To date, the missed diagnosis rate of pulmonary hypertension (PH) was high, and there has been limited development of a rapid, simple, and effective way to screen the disease. The purpose of this study is to develop a deep learning approach to achieve rapid detection of possible abnormalities in chest radiographs suggesting PH for screening patients suspected of PH. METHODS: We retrospectively collected frontal chest radiographs and the pulmonary artery systolic pressure (PASP) value measured by Doppler transthoracic echocardiography from 762 patients (357 healthy controls and 405 with PH) from three institutes in China from January 2013 to May 2019. The wohle sample comprised 762 images (641 for training, 80 for internal test, and 41 for external test). We firstly performed a 8-fold cross-validation on the 641 images selected for training (561 for pre-training, 80 for validation), then decided to tune learning rate to 0.0008 according to the best score on validation data. Finally, we used all the pre-training and validation data (561+80 = 641) to train our models (Resnet50, Xception, and Inception V3), evaluated them on internal and external test dataset to classify the images as having manifestations of PH or healthy according to the area under the receiver operating characteristic curve (AUC/ROC). After that, the three deep learning models were further used for prediction of PASP using regression algorithm. Moreover, we invited an experienced chest radiologist to classify the images in the test dataset as having PH or not, and compared the prediction accuracy performed by deep learing models with that of manual classification. RESULTS: The AUC performed by the best model (Inception V3) achieved 0.970 in the internal test, and slightly declined in the external test (0.967) when using deep learning algorithms to classify PH from normal based on chest X-rays. The mean absolute error (MAE) of the best model for prediction of PASP value was smaller in the internal test (7.45) compared to 9.95 in the external test. Manual classification of PH based on chest X-rays showed much lower AUCs compared to that performed by deep learning models both in the internal and external test. CONCLUSIONS: The present study used deep learning algorithms to classify abnormalities suggesting PH in chest radiographs with high accuracy and good generalizability. Once tested prospectively in clinical settings, the technology could provide a non-invasive and easy-to-use method to screen patients suspected of having PH.

Vascular endothelial growth factor concentration in vitreous humor of patients with severe proliferative diabetic retinopathy after intravitreal injection of conbercept as an adjunctive therapy for vitrectomy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is a progressive stage of diabetic retinopathy featured by the formation of neovascular and proliferative membrane. Vascular endothelial growth factor (VEGF) acts as a pivot factor in the development of neovascularization. This study was to investigate the changes of intravitreal VEGF concentrations of severe PDR after intravitreal injection of conbercept (IVC) and its potential advantages to the following vitrectomy. METHODS: This was a prospective, interventional, randomized controlled study. Sixty eyes (60 patients) with severe PDR and 20 eyes from 20 patients with rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy were enrolled in this study. PDR eyes were randomly assigned to three groups by sortation randomization method with 20 eyes in each based on the interval of preoperative IVC (group A: 7 days, group B: 14 days, group C: non-IVC). Another 20 eyes without diabetes were enrolled as the non-diabetic control group (group D), receiving PPV directly. Vitreous specimens of all 80 patients were collected and evaluated afterwards. The intravitreal VEGF concentration of the four groups, and the total surgical time and the intraoperative bleeding rate of the PDR groups were recorded. RESULTS: The mean intravitreal VEGF concentrations of groups A-D were 66.6 ±â€Š43.3, 93.1 ±â€Š52.3, 161.4 ±â€Š106.1 and 1.8 ±â€Š1.2 pg/mL, respectively. It increased significantly in PDR patients (groups A, B and C) (P = 0.002, <0.001, and <0.001, respectively). PDR patients with preoperative IVC (groups A and B) presented significantly lower VEGF concentrations (P < 0.001 and 0.001), intraoperative bleeding rates (P = 0.004) and total surgical time (P < 0.001, P = 0.003) compared with group C. No statistical differences were presented between groups A and B on the three parameters. CONCLUSION: Seven days and 14 days of preoperative IVC are equally efficient and safe for the vitrectomy of severe PDR patients through decreasing vitreous VEGF concentrations, intraoperative bleeding rate and total surgical times.

Fundus manifestations and HIV viral loads of AIDS patients before and after HAART.

AIM: To investigate the fundus manifestations and human immunodeficiency virus (HIV) viral loads of acquired immune deficiency syndrome (AIDS) patients before and after highly active antiretroviral therapy (HAART). METHODS: This retrospective study included 21 AIDS patients (42 eyes) who presented to the Department of Ophthalmology, Peking Union Medical College Hospital, from 2007 to 2011. Among the patients, 16 showed a good response to HAART, 3 presented drug resistance and 2 were pre-HAART. All patients underwent comprehensive ophthalmic examinations. The HIV viral loads and the CD4+ T-cell counts were also determined. RESULTS: The best-corrected visual acuity (BCVA) of 38 eyes (19 patients) was improved, and cytomegalovirus retinitis (CMVR) in 5 eyes (3 patients) regressed after HAART. Furthermore, 16 patients treated with effective HAART had decreased plasma HIV viral loads (<78 copies/mL) and increased CD4+ T-cell counts (343±161 cells/µL, P<0.005), but the HIV viral load in tears was still detected at 2404 copies/mL. The CD4+ T-cell count was lower in the CMVR group than in the non-CMVR group (P=0.022), but the HIV viral load in the tears was not significantly different between the two groups (P=0.439). CONCLUSION: Most patients with AIDS show a good viral response with a decreased HIV viral load and an increased CD4+ T-cell count in plasma after HAART. However, the HIV viral load remain quite high in the tear samples. Based on our results, we suggest that AIDS patients undergo long-term HAART that should not be interrupted.

Varicella-zoster virus as a causative agent of acute retinal necrosis in younger patients.

BACKGROUND: Herpes virus is considered to be the pathogen of acute retinal necrosis (ARN) infection. Previous studies have found that patients with ARN caused by the varicella-zoster virus (VZV) are often older, and patients with herpes simplex virus (HSV) induced ARN are considerably younger. However, in our clinical work, we find that VZV is also a pathogen in younger ARN patients. We, therefore, aimed to analyze the common etiology of younger ARN patients. METHODS: A retrospective analysis was made of 20 eyes (18 patients) diagnosed as having ARN in the Department of Ophthalmology of Peking Union Medical College Hospital from 2014 to 2016. All patients were reviewed for demographic data, clinical course, clinical manifestations, time from onset to initial physician visit, duration of follow-up, visual acuity at both presentation and final visit, and treatment strategies. A paired t test was used to compare visual acuity between the presenting vision and those of final follow-up. Vitreous or aqueous specimens from 18 eyes of 18 patients were analyzed with multiplex polymerase chain reaction (mPCR)/quantitative PCR (qPCR) and xTAG-liquid chip technology (xTAG-LCT) to determine the causative virus of ARN. RESULTS: Final best visual acuity (BCVA) improved significantly from 1.36 ±â€Š0.95 (median 20/400) to 0.95 ±â€Š0.82 (median 20/100) (t = 2.714, P = 0.015) after systemic and intravitreal antiviral treatment combined with or without pars plana vitrectomy. PCR and xTAG-LCT results showed four of the five samples in the younger group (32.2 ±â€Š5.2 years) and 12 of the 13 samples in the senior group (53.6 ±â€Š4.9 years) were positive for VZV, and two of the five samples in the younger group were positive for HSV-1. CONCLUSIONS: This study demonstrates that VZV is also a common causative virus for ARN in younger patients. Considering this finding, a systemic antiviral treatment protocol should be immediately changed to intravenous ganciclovir when the patient does not respond to acyclovir before determining the causative virus, especially in younger patients.

LncRNA LINC00460 promotes tumor growth of human lung adenocarcinoma by targeting miR-302c-5p/FOXA1 axis.

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers, especially lung adenocarcinoma (LC). In the present study, we aimed to investigate the role and potential mechanism of lncRNA long intergenic non-protein coding RNA 460 (LINC00460) in LC progression using human tissues and cell lines. We observed that LINC00460 was increased in lung adenocarcinoma tissues and cells in comparison to their corresponding controls. Moreover, overexpression of LINC00460 indicated the poor prognosis of lung adenocarcinoma patients. In addition, silencing LINC00460 was able to suppress lung adenocarcinoma cell growth in vitro and in vivo. Rescue assay confirmed that LINC00460 contributed to lung adenocarcinoma progression by regulating miR-302c-5p/FOXA1 signal pathway. In conclusion, LINC00460 promotes LC progression by competitively binding miR-302c-5p and regulating FOXA1 signal pathway. Our findings reveal that LINC00460 may be a potential prognostic biomarker and a candidate target for LC therapy.

Low-density point eating algorithm for surface reconstruction from dense scans.

We present a low-density point eating algorithm for surface reconstruction from dense scans. First, the density map for each scan is estimated and the boundary densities are down-weighted. Subsequently, the poorly scanned low-density overlapping points are eaten up based on a user-specified threshold. Finally, the overlapping areas are thinned by using the moving least-squares operator and the homogeneous points are weighted averaged. The new algorithm can extract smooth but detailed point set surfaces that are as close as possible to the ground truth. The good performance of the new algorithm is demonstrated by comparison with several advanced surface reconstruction algorithms.

Inverted Internal Limiting Membrane Flap Technique for Repair of Large Macular Holes: A Short-term Follow-up of Anatomical and Functional Outcomes.

BACKGROUND: Inverted internal limiting membrane (ILM) flap technique has recently been reported in a limited number of studies as an effective surgical technique for the management of large macular holes (MHs) with fair MH closure rates as well as gains in visual acuity. In the current study, longitudinal changes in multi-focal electroretinogram (mfERG) responses, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated in eyes with large MHs managed by this technique. METHODS: A prospective noncontrolled interventional study of eight patients (eight eyes) with large MHs (minimum diameter >400 µm) was conducted. All MHs were treated with pars plana vitrectomy and indocyanine green-assisted inverted ILM flap technique. SD-OCT images were used to assess the anatomical outcomes of surgery while BCVA and mfERG were used to evaluate the functional outcomes during a 3-month follow-up. RESULTS: All patients underwent successful intended manipulation and translocation of the ILM flap without flap dislocation and achieved complete anatomical closure. Partial microstructural reconstruction, demonstrated on SD-OCT as restoration of the external limiting membrane and the ellipsoid zone, was observed in all cases as early as 1 month after surgery. Functionally, as compared to baseline, all patients showed improvements in BCVA and all but one in mfERG response during follow-up. However, Pearson's test revealed no significant correlations between BCVA and mfERG responses of the fovea and of the macular area at each evaluation time point. CONCLUSIONS: Inverted ILM flap technique appears to be a safe and effective approach for the management of large idiopathic MHs with favorable short-term anatomical and functional results. Postoperative reconstruction of the microstructure generally shows good consistency with improvements in both BCVA and mfERG response, of which the latter might be a supplement for the former in postoperative functional follow-up.

Twist mediates an aggressive phenotype in human colorectal cancer cells.

Epithelial-mesenchymal transition (EMT) is a crucial process providing cancer cells with the ability to migrate and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype and chemoresistance. Twist is a transcription factor that regulates EMT in a various cancer cells, including colorectal cancer (CRC). Our study was done to determine the role of Twist in mediating aggressive phenotype in CRC. Human CRC cell lines were transduced with a retroviral Twist construct or vector control. Migration and invasion abilities were determined in vitro using modified Boyden chamber assays. Mammosphere formation assay was performed to detect CSC characteristics. EMT and CSC markers were detected using western blotting and RT-PCR. Chemosensitivity to oxaliplatin of the transfected cells were determined by the MTT assay. Human CRC specimens were stained for Twist and P-gp expression. Twist overexpression triggered EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration, invasion and mammosphere formation abilities. In addition, Twist-overexpressing CRC cells were more chemo-resistant to oxaliplatin than control cells. Furthermore, Twist over-expression increased P-gp expression in CRC cells, which is a transmembrane glycoprotein conferred multidrug-resistance phenotype to various cancer cells. Importantly, Twist and P-gp were expressed correlatively in human CRC specimens. Thus, Twist is a potential therapeutic target in metastatic CRC.

Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China.

OBJECTIVE: There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. METHODS: A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. RESULTS: The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. CONCLUSIONS: Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

[Think highly of the diagnose and therapy of ocular pathological changes in the HIV infected and AIDS patients].

Acquired immune deficiency syndrome (AIDS) is a kind of fatal disease which involve multiple organs and the public health of global intention. The incidence rate in China is escalating obviously. Currently there is lack of large samples and long-term systematic observations of ocular pathological changes in the human immunodeficiency virus (HIV) infected and AIDS patients. Diagnostic errors and missed diagnosis still exist in hospitals, even in some advanced hospitals. They delay the therapy of patients, also easily result in hospital acquired infections. It is notable that there is insufficient attention to preoperative test of anti-HIV in some hospitals, especially in outpatient surgeries. Therefore potential iatrogenic infection risks are hidden. Some clinical doctors are afraid of AIDS patients, therefore they are lack of subjective initiative to comprehensively examination and treatment the patients. For the past few years, highly active antiretroviral therapy is widely used, AIDS related morbidity and mortality is significantly reduced, and the prevalence rate of ocular complications decreased from 55% to 95%. But due to the HIV/AIDS patient volume increased year by year, and the survival rate raised, prolonged survival, results in the increase of the absolute number of patients with ocular complications. Therefore it is critical to pay attention to the HIV/AIDS ocular lesions in the diagnosis and treatment of iatrogenic infection.

[Fundus manifestation and treatment of Takayasu's arteritis].

OBJECTIVE: To evaluate the fundus manifestation and treatment of Takayasu's arteritis. METHODS: Retrospective case series was taken to study the clinical data of 15 patients (30 eyes) diagnosed with Takayasu's arteritis at Peking Union Medical College Hospital from 1992 to 2010. Examinations included visual acuity, slit-lamp, fundus, fundus fluorescein angiography (FFA), large vascular ultrasound, digital subtraction angiography (DSA), erythrocyte sedimentation rate (ESR) and reactive protein C (CRP). All patients were given systemic corticosteroids, immunosuppressive agents and anticoagulants. Three patients (4 eyes) received retinal photocoagulation, and 1 patient (1 eye) received vitrectomy combined with silicone oil tamponade. RESULTS: Fifteen cases aged 13 - 49 years [mean (33.6 ± 11.1) years] were enrolled, including 2 male and 13 female patients. Two patients recognized by initial presentation of impaired vision prior to the diagnosis of Takayasu's arteritis. Visual acuity: light perception -0.05, 6 eyes; 0.1 - 0.5, 4 eyes; 0.6 - 1.0, 5 eyes; and above 1.0, 15 eyes. The fundus examination revealed chronic ischemic retinopathy in 16 eyes characterized by microaneurysms, cotton-wool spots and peripapillary arteriovenous anastomosis, and complicated by vitreous hemorrhage, retinal detachment and proliferative retinopathy at the late stage. There was hypertensive retinopathy in 14 eyes with features of narrow retinal artery, arteriovenous crossing signs and retinal hemorrhage. FFA showed prolonged arm-to-retina circulation time and retinal circulation time, microaneurysms and neovasculature. Six cases were classified as brachiocephalic arteritis, and 9 patients belonged to extensive arteritis. ESR increased in 9 patients and CRP elevated in 5 patients. Capillary non-perfusion areas in 4 eyes subsided after retinal photocoagulation, and retina reattached in 1 eye after vitrectomy with visual acuity improved from light perception to count finger. CONCLUSIONS: Fundus manifestation of Takayasu's arteritis is usually characterized by chronic ischemic retinopathy and hypertensive retinopathy, and complications such as vitreous hemorrhage, retinal detachment and proliferative retinopathy occur at advanced stage. The first symptom in some patients can be impaired vision. The prognosis could be improved if ophthalmologists know fundus characteristics of Takayasu's arteritis and give timely and correct diagnosis and treatment.