Discovery of hydroxamate as a promising scaffold dually inhibiting metallo- and serine-ß-lactamases.

The bacterial infection mediated by ß-lactamases MßLs and SßLs has grown into an emergent health threat, however, development of a molecule that dual inhibits both MßLs and SßLs is challenging. In this work, a series of hydroxamates 1a-g, 2a-e, 3a-c, 4a-c were synthesized, characterized by 1H and 13C NMR and confirmed by HRMS. Biochemical assays revealed that these molecules dually inhibited MßLs (NDM-1, IMP-1) and SßLs (KPC-2, OXA-48), with an IC50 value in the range of 0.64-41.08 and 1.01-41.91 µM (except 1a and 1d on SßLs, IC50 > 50 µM), and 1f was found to be the best inhibitor with an IC50 value in the range of 0.64-1.32 and 0.57-1.01 µM, respectively. Mechanism evaluation indicated that 1f noncompetitively and irreversibly inhibited NDM-1 and KPC-2, with Ki value of 2.5 and 0.55 µM, is a time- and dose-dependent inhibitor of both MßLs and SßLs. MIC tests shown that all hydroxamates increased the antimicrobial effect of MER on E. coli-NDM-1 and E. coli-IMP-1 (expect 1b, 1d, 1g and 2d), resulting in a 2-8-fold reduction in MICs of MER, 1e-g, 2b-d, 3a-c and 4b-c decreased 2-4-fold MICs of MER on E. coli-KPC-2, and 1c, 1f-g, 2a-c, 3b, 4a and 4c decreased 2-16-fold MICs of MER on E. coli-OXA-48. Most importantly, 1f-g, 2b-c, 3b and 4c exhibited the dual synergizing inhibition against both E. coli-MßLs and E. coli-SßLs tested, resulting in a 2-8-fold reduction in MICs of MER, and 1f was found to have the best effect on the drug-resistant bacteria tested. Also, 1f shown synergizing antimicrobial effect on five clinical isolates EC04, EC06, EC08, EC10 and EC24 that produce NDM-1, resulting in a 2-8-fold reduction in MIC of MER, but its effect on E. coli and K. pneumonia-KPC-NDM was not to be observed using the same dose of inhibitor. Mice tests shown that the monotherapy of 1f or 4a in combination with MER significantly reduced the bacterial load of E. coli-NDM-1 and E. coli-OXA-48 cells in liver and spleen, respectively. The discovery in this work offered a promising bifunctional scaffold for creating the specific molecules that dually inhibit MßLs and MßLs, in combating antibiotic-resistant bacteria.

[Differential Analysis of Macular Structure and Microcirculation in Both Eyes of Patients With Myopic Anisometropia].

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.

Exploration of Hippocampal Functional Connectivity Alterations in Patients with High Myopia via Seed-Based Functional Connectivity Analysis.

Aim: The objective of this study was to examine changes in functional connectivity (FC) in the hippocampus among patients with high myopia (HM) compared to healthy controls (HCs) through the utilization of seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) was conducted on a sample of 82 patients diagnosed with high myopia (HM) and 59 HCs. The two groups were matched based on age, weight and other relevant variables. Using seed-based FC analysis to detect alterations in hippocampal FC patterns in HM patients and HCs. Furthermore, a correlation analysis was performed to examine the associations between the mean functional connectivity (FC) signals in various brain regions of patients with HM and their corresponding clinical manifestations. Results: The FC values in the left temporal pole-temporal gyrus (L-TPOsup), right hippocampus (R-HIP), left medial temporal gyrus (L-MTG) and left hippocampus in HM patients were significantly lower than those of healthy subjects. In the left temporal pole-superior temporal gyrus (L-TPOsup), right orbital part of middle frontal gyrus (RO-MFG), left fusiform gyrus (L-FG), left cerebellum superior (L-Cbe6), left middle temporal gyrus (L-MTG), right thalamus (R-THA), and right hippocampus, FC values were also significantly lower. Conclusion: Brain dysfunction was observed in various regions of the HM patients, suggesting the existence of neurobiological alterations that could lead to impairments in visual cognition, movement, emotional processing, and visual memory.

Machine learning analysis reveals aberrant dynamic changes in amplitude of low-frequency fluctuations among patients with retinal detachment.

Background: There is increasing evidence that patients with retinal detachment (RD) have aberrant brain activity. However, neuroimaging investigations remain focused on static changes in brain activity among RD patients. There is limited knowledge regarding the characteristics of dynamic brain activity in RD patients. Aim: This study evaluated changes in dynamic brain activity among RD patients, using a dynamic amplitude of low-frequency fluctuation (dALFF), k-means clustering method and support vector machine (SVM) classification approach. Methods: We investigated inter-group disparities of dALFF indices under three different time window sizes using resting-state functional magnetic resonance imaging (rs-fMRI) data from 23 RD patients and 24 demographically matched healthy controls (HCs). The k-means clustering method was performed to analyze specific dALFF states and related temporal properties. Additionally, we selected altered dALFF values under three distinct conditions as classification features for distinguishing RD patients from HCs using an SVM classifier. Results: RD patients exhibited dynamic changes in local intrinsic indicators of brain activity. Compared with HCs, RD patients displayed increased dALFF in the bilateral middle frontal gyrus, left putamen (Putamen_L), left superior occipital gyrus (Occipital_Sup_L), left middle occipital gyrus (Occipital_Mid_L), right calcarine (Calcarine_R), right middle temporal gyrus (Temporal_Mid_R), and right inferior frontal gyrus (Frontal_Inf_Tri_R). Additionally, RD patients showed significantly decreased dALFF values in the right superior parietal gyrus (Parietal_Sup_R) and right paracentral lobule (Paracentral_Lobule_R) [two-tailed, voxel-level p < 0.05, Gaussian random field (GRF) correction, cluster-level p < 0.05]. For dALFF, we derived 3 or 4 states of ALFF that occurred repeatedly. There were differences in state distribution and state properties between RD and HC groups. The number of transitions between the dALFF states was higher in the RD group than in the HC group. Based on dALFF values in various brain regions, the overall accuracies of SVM classification were 97.87, 100, and 93.62% under three different time windows; area under the curve values were 0.99, 1.00, and 0.95, respectively. No correlation was found between hamilton anxiety (HAMA) scores and regional dALFF. Conclusion: Our findings offer important insights concerning the neuropathology that underlies RD and provide robust evidence that dALFF, a local indicator of brain activity, may be useful for clinical diagnosis.

Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis.

Aim: This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis. Methods: Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis. Results: In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05). Conclusion: Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Exploration of abnormal dynamic spontaneous brain activity in patients with high myopia via dynamic regional homogeneity analysis.

Aim: Patients with high myopia (HM) reportedly exhibit changes in functional brain activity, but the mechanism underlying such changes is unclear. This study was conducted to observe differences in dynamic spontaneous brain activity between patients with HM and healthy controls (HCs) via dynamic regional homogeneity (dReHo) analysis. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 82 patients with HM and 59 HCs who were closely matched for age, sex, and weight. The dReHo approach was used to assess local dynamic activity in the human brain. The association between mean dReHo signal values and clinical symptoms in distinct brain areas in patients with HM was determined via correlation analysis. Results: In the left fusiform gyrus (L-FG), right inferior temporal gyrus (R-ITG), right Rolandic operculum (R-ROL), right postcentral gyrus (R-PoCG), and right precentral gyrus (R-PreCG), dReHo values were significantly greater in patients with HM than in HCs. Conclusion: Patients with HM have distinct functional changes in various brain regions that mainly include the L-FG, R-ITG, R-ROL, R-PoCG, and R-PreCG. These findings constitute important evidence for the roles of brain networks in the pathophysiological mechanisms of HM and may aid in the diagnosis of HM.

Abnormal Functional Connectivity Between Cerebral Hemispheres in Patients With High Myopia: A Resting FMRI Study Based on Voxel-Mirrored Homotopic Connectivity.

Purpose: To study the changes in functional connections between the left and right hemispheres of patients with high myopia (HM) and healthy controls (HCs) by resting functional magnetic resonance imaging (fMRI) based on voxel-mirrored homotopic connectivity (VMHC). To study the changes in resting-state functional connectivity (rsFC) between the left and right hemispheres of patients with HM and healthy controls (HCS) at rest by using resting functional magnetic resonance imaging (fMRI) based on voxel-mirror homotopy connectivity (VMHC). Patients and Methods: A total of 89 patients with HM (41 men and 48 women) and 59 HCs (24 men and 35 women) were collected and matched according to gender, age, and education level. The VMHC method was used to evaluate the changes in rsFC between cerebral hemispheres, and a correlation analysis was carried out to understand the differences in brain functional activities between the patients with HM and the HCs. Results: Compared with the HCs, the VMHC values of the putamen and fusiform in the HM group were significantly lower (voxel-level p < 0.01, Gaussian random field correction cluster level p < 0.05). Conclusion: This study preliminarily confirmed the destruction of interhemispheric functional connection in some brain regions of the patients with HM and provided effective information for clarifying the neural mechanism of patients with HM.

Dihydroxyphenyl-substituted thiosemicarbazone: A potent scaffold for the development of metallo-ß-lactamases inhibitors and antimicrobial.

The superbug infection mediated by metallo-ß-lactamases (MßLs) has grown into anemergent health threat, and development of MßL inhibitors is an ideal strategy to combat the infection. In this work, twenty-five thiosemicarbazones 1a-e, 2a-e, 3a-e, 4a-d, 5a-d and 6a-b were synthesized and assayed against MßLs ImiS, NDM-1 and L1. The gained molecules specifically inhibited NDM-1 and ImiS, exhibiting an IC50 value in the range of 0.37-21.35 and 0.45-8.76 µM, and 2a was found to be the best inhibitor, with an IC50 of 0.37 and 0.45 µM, respectively, using meropenem (MER) as substrate. Enzyme kinetics and dialysis tests revealed and confirmed by ITC that 2a is a time-and dose-dependent inhibitor of ImiS and NDM-1, it competitively and reversibly inhibited ImiS with a Ki value of 0.29 µM, but irreversibly inhibited NDM-1. Structure-activity relationship disclosed that the substitute dihydroxylbenzene significantly enhanced inhibitory activity of thiosemicarbazones on ImiS and NDM-1. Most importantly, 1a-e, 2a-e and 3a-b alone more strongly sterilized E. coli-ImiS and E. coli-NDM-1 than the MER, displaying a MIC value in the range of 8-128 µg/mL, and 2a was found to be the best reagent with a MIC of 8 and 32 µg/mL. Also, 2a alone strongly sterilized the clinical isolates EC01, EC06-EC08, EC24 and K. pneumonia-KPC-NDM, showing a MIC value in the range of 16-128 µg/mL, and exhibited synergistic inhibition with MER on these bacteria tested, resulting in 8-32-fold reduction in MIC of MER. SEM images shown that the bacteria E. coli-ImiS, E. coli-NDM-1, EC24, K. pneumonia-KPC and K. pneumonia-KPC-NDM treated with 2a (64 µg/mL) suffered from distortion, emerging adhesion between individual cells and crumpled membranes. Mice tests shown that monotherapy of 2a evidently limited growth of EC24 cells, and in combination with MER, it significantly reduced the bacterial load in liver and spleen. Docking studies suggest that the 2,4-dihydroxylbenzene of 2a acts as zinc-binding group with the Zn(II) and the residual amino acids in CphA active center, tightly anchoring the inhibitor at active site. This work offered a promising scaffold for the development of MßLs inhibitors, specifically the antimicrobial for clinically drug-resistant isolates.

Abnormal Large-Scale Neuronal Network in High Myopia.

Aim: Resting state functional magnetic resonance imaging (rs-fMRI) was used to analyze changes in functional connectivity (FC) within various brain networks and functional network connectivity (FNC) among various brain regions in patients with high myopia (HM). Methods: rs-fMRI was used to scan 82 patients with HM (HM group) and 59 healthy control volunteers (HC group) matched for age, sex, and education level. Fourteen resting state networks (RSNs) were extracted, of which 11 were positive. Then, the FCs and FNCs of RSNs in HM patients were examined by independent component analysis (ICA). Results: Compared with the HC group, FC in visual network 1 (VN1), dorsal attention network (DAN), auditory network 2 (AN2), visual network 3 (VN3), and sensorimotor network (SMN) significantly increased in the HM group. FC in default mode network 1 (DMN1) significantly decreased. Furthermore, some brain regions in default mode network 2 (DMN2), default mode network 3 (DMN3), auditory network 1 (AN1), executive control network (ECN), and significance network (SN) increased while others decreased. FNC analysis also showed that the network connection between the default mode network (DMN) and cerebellar network (CER) was enhanced in the HM group. Conclusion: Compared with HCs, HM patients showed neural activity dysfunction within and between specific brain networks, particularly in the DMN and CER. Thus, HM patients may have deficits in visual, cognitive, and motor balance functions.

[Effects of Intravitreal Injection of Anti-vascular Endothelial Growth Factor Drugs on Ocular Blood Vessels and Blood Flow in Patients with Diabetic Retinopathy].

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.

BMP-2 alleviates heart failure with type 2 diabetes mellitus and doxorubicin-induced AC16 cell injury by inhibiting NLRP3 inflammasome-mediated pyroptosis.

Chronic heart failure (CHF) and diabetes mellitus are associated with morbidity and mortality. CHF and diabetes generally simultaneously occur, resulting in adverse outcomes. Diabetes complicates cardiomyopathy and exacerbates heart failure conditions. An increase in natriuretic peptides, including atrial natriuretic peptide (ANP), and another endsogenously generated peptide, brain natriuretic peptide (BNP), serves an essential role in CHF. The aim of this study was to explore the molecular regulation between bone morphogenetic protein-2 (BMP-2) and ANP or BNP in diabetes-associated cardiomyopathy. In total, 25 serum samples were collected from patients with CHF with or without type 2 diabetes mellitus to compare with 25 controls. Cardiomyopathy and hyperglycemia were induced in rats by doxorubicin and streptozotocin, respectively. AC16 cells were used to study molecular mechanisms. BMP, ANP and BNP concentration in patients and rats were measured by ELISA. Flow cytometry was performed to analyze cell pyroptosis and ROS production. Reverse transcription-quantitative PCR and western blotting were used to examine mRNA and protein expression of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), pro-caspase-1, caspase-1 (p20) and gasdermin D. BMP-2 was negatively correlated with ANP and BNP in CHF patients with type 2 diabetes mellitus. Similar results were obtained in rats and AC16 cells. BMP-2 decreased the NLRP3 inflammasome activation and cell pyroptosis. The present study found evidence that the cardioprotective effects of BMP-2 act through ANP and BNP both in vivo and in vitro. BMP-2 inhibits inflammasome formation. The results suggested that BMP-2 may serve as a novel therapeutic target for the treatment of diabetic heart conditions.

GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy.

BACKGROUND: The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC. METHODS: Whole-exome sequencing (WES) and long-read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied. RESULTS: We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy. INTERPRETATION: These phenotypes enrich the class of features associated with NOTCH2NLC-related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.

Impaired Interhemispheric Synchrony in Bronchial Asthma.

PURPOSE: Converging evidence demonstrated that bronchial asthma (BA) individuals with hypoxia were associated with functional and morphological reorganization in the brain. However, the alterations of the interhemispheric functional connectivity in BA individuals remain unknown. The purpose of this study was to assess the interhemispheric functional connectivity changes in individuals with hypoxia due to middle-aged BA using voxel-mirrored homotopic connectivity (VMHC) methods. METHODS: In total, 31 BA individuals and 30 healthy controls (HCs) closely matched in age, sex, and education underwent resting-state magnetic resonance imaging (MRI) scans. VMHC analysis was performed to investigate differences in interhemispheric functional connectivity between the two groups. Then, a seed-based resting-state functional connectivity (rsFC) analysis was conducted to further reveal the abnormal functional connectivity between the altered VMHC regions and the whole brain. RESULTS: Compared with HCs, BA individuals had significantly lower VMHC values in the bilateral basal ganglia/thalamus/insula, cuneus/calcarine/lingual gyrus, precentral and postcentral gyrus. [voxel level P < 0.01, Gaussian random field (GRF) correction, cluster level P < 0.05]. Taking VMHC altered brain areas as seed points, the rsFC values of left insula/supramarginal/postcentral gyrus (PostCG)/inferior parietal lobule (IPL) brain areas in BA were increased. CONCLUSION: The abnormal resting-state functional connectivity of middle-aged BA is altered in specific brain regions related to the basal ganglia network, visual network, and sensorimotor network, which may be related to the neuropathogenesis of asthma patients. Furthermore, these VMHC and FC values may be important clinical indicators for the diagnosis and treatment of asthma patients.

Evidence of cortical thickness reduction and disconnection in high myopia.

High myopia (HM) is associated with impaired long-distance vision. accumulating evidences reported that abnormal visual experience leads to dysfunction in brain activity in HM even corrected. However, whether the long-term of abnormal visual experience lead to neuroanatomical changes remain unknown, the aim at this study is to investigate the alternation of cortical surface thickness in HM patients. 82 patients with HM (HM groups), 57 healthy controls (HC groups) were recruited. All participants underwent high-resolution T1 and resting-state functional magnetic resonance imaging (MRI) scans. The cortical thickness analysis was preformed to investigate the neuroanatomical changes in HM patients using computational anatomy toolbox (CAT 12) toolbox. Compare with HCs, HM patients showed decreased the cortical surface thickness in the left middle occipital gyrus (MOG), left inferior parietal lobule (IPL), right inferior temporal gyrus (ITG), right precuneus, right primary visual area 1 (V1), right superior temporal gyrus (STG), right superior parietal lobule (SPL), right occipital pole, and right the primary motor cortex (M1), and increased to the parietal operculum (OP4) (P < 0.01, FWE-corrected), the mean cortical thickness of right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC) and right subcallosal cortex showed negatively correlation between clinical variables (axis length (ALM), the average macular thickness (AMT), keratometer (KER) 1, KER2, the mean KER, the mean macular fovea thickness (MFK), the refractive diopter) in HM patients. Our result mainly provided an evidence of cortical thickness reduction and disconnection in visual center and visual processing area, and cortical thickness increase in left multimodal integration region in HM patients. This may provide important significance of the study of the neural mechanism of HM.

Vitrectomy with internal limiting membrane peeling versus its flap insertion for macular hole in high myopia: a Meta-analysis.

AIM: To compare the anatomic and functional outcomes between vitrectomy with internal limiting membrane (ILM) peeling and internal ILM flap insertion technique for high myopia macular hole (MH). METHODS: PubMed, Cochrane Library, EMBASE, and CNKI were systematically searched, and all studies involved MH were included. The closure rate of MH and the postoperative best-corrected visual acuity (BCVA) at 6mo after the initial surgery were the primary measures. All statistical tests were performed in Review Manager 5.3. RESULTS: Five studies that included 151 eyes of 151 patients were finally included, all of which were retrospectively comparative studies. Between the pars plana vitrectomy (PPV) with ILM peeling surgery and the ILM insertion technique, the latter had significantly better efficacy with respect to the closure rate of MH (OR=21.32, 95%CI=7.25-62.67, P<0.001); However, regarding BCVA at 6mo after the initial surgery in MH, there was no statistical significance between the groups (OR=-0.04, 95%CI=-0.22-0.14, P=0.66). In addition, regarding the rate of retinal reattachment after the initial surgery, the two different methods were not significantly different (OR=2.22, 95%CI=0.34-14.32, P=0.4). CONCLUSION: Both ILM peeling and ILM insertion technique could significantly improve anatomic outcomes of MH in high myopia with or without retinal detachment (RD), and anatomic outcomes are more effective. However, there is no statistical significance in BCVA at 6mo after the initial surgery in MH, or in the rate of retinal reattachment after the first surgery, between the two methods.

[Research Advances in Ocular Myasthenia Gravis].

Ocular myasthenia gravis(OMG)is an autoimmune disease caused by neuromuscular junction transmission disorders and manifested mainly as fluctuating blepharoptosis and diplopia,with the extraocular muscles as the main involveed sites.While the pathogenesis of OMG remains unclear,some antibodies,complements,and cytokines may be the contributing factors.The diagnosis and treatment of OMG have been defined in recent years.This article reviews the pathogenesis,diagnosis,and treatment of OMG.

[Advances in Retinopathy of Prematurity].

Retinopathy of prematurity(ROP)is a pathological neovascularization with fibrotic changes in the fundus of premature infants.It is a major cause of preventable blindness in children in both developing and developed countries.Treatment of ROP has long been a hot research topic in ophthalmology and pediatrics.With a clearer knowledge of the pathogenesis of ROP,more basic and clinical studies have been carried out.The anti-vascular endothelial growth factor therapy and surgical treatment have become mature strategies,and a variety of therapeutic drugs including insulin-like growth factor-1,transforming growth factor-ß,polyunsaturated fatty acids,and ß-adrenergic receptor blockers have been developed.This article reviews the recent advances in ROP.

Elevated atmospheric CO2 might increase the health risk of long-term ingestion of leafy vegetables cultivated in residual DDT polluted soil.

Residual dichlorodiphenyltrichloroethane (DDT) in the environment and a continuously increasing atmospheric carbon dioxide (CO2) concentration are two issues that have received a lot of attention. This study was conducted using a pot experiment to investigate the interactive effects of elevated CO2 and DDT on the uptake of DDT, the physiological responses and the resulting health risks in three vegetables. These vegetables included Brassica juncea var. foliosa Bailey (B. Bailey), Brassica campestris L. var. communis Tsen et Lee Suzhou Qing (B. Lee) and Brassica campestris L. ssp. pekinensis (Lour.) Olsson Chun Dawang (B. Olsson). Two levels of CO2 and four DDT treatment levels were set up. Results showed 5 mg kg-1 DDT significantly reduced the shoot biomass of B. Bailey when compared to 0 mg kg-1 DDT treatment under ambient CO2 condition. Elevated CO2 concentration stimulated the growth of B. Bailey and B. Lee, increased the DDT uptake in the shoots of both vegetables and the values of some photosynthesis indices, and triggered the activity of peroxidase and catalase in the shoots when compared to the related ambient CO2 treatment. Elevated CO2 concentration increased the values of hazard indexes for non-carcinogenic and cancer risks of all vegetables when compared to the individual ambient CO2 treatment (each of vegetable has an ambient CO2 treatment), especially for B. Bailey (increase amplitude of 123.81%-127.78% at 5 mg kg-1 DDT). Long-term ingestion with these DDT-polluted vegetables might result in an elevated carcinogenic risk and elevated atmospheric CO2 may enhance the non-carcinogenic and carcinogenic risks.

[Mechanism of Th1/Th2 Cytokines in HLA-DQ8 Transgenic Mice Model of Ocular Experimental Autoimmune Myasthenia Gravis].

Objective To analyze the levels of cytokines (IL-2,IFN-γ,IL-6,IL-10) associated with Th1 and Th2 cells in HLA-DQ8 transgenic mice model of ocular experimental autoimmune myasthenia gravis (oEAMG) induced by recombinant H-AChR γ subunit immunization.Methods DQ8 mice were immunized with 20 µg of AChR γ subunit,20 µg of crude E. coli extract (E. coli group),or complete Freund's adjuvant (CFA) only (CFA group). All mice were immunized on days 0,30,and 60. Mice were euthanized 28 days after the third immunization,and draining lymph node cells (LNC) and spleen lymphocytes were cultured in vitro. The supernatant was collected to observe the interleukin(IL)-2,interferon(IFN)-γ,IL-6,IL-10 production by ELISA.Results LNCs and spleen lymphocytes of H-AChR γ subunit-immunized mice exhibited significantly enhanced IFN-γ (F=76.332,P<0.001;F=34.865,P<0.001) and IL-2 (F=42.835,P<0.001;F=38.030,P<0.001),which associated with Th1 cells,as compared to E. coli group and CFA group. There were no significant differences in IL-6 (F=1.325,P=0.284;F=1.935,P=0.166) and IL-10 (F=0.908,P=0.417;F=1.189,P=0.322) levels,which secreted by Th2 cells,among these three groups.Conclusion Th1 cytokines play key roles in the pathogenesis of oEAMG,while the mechanism of Th2 cytokines for oEAMG remains unclear.