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ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9% ee, >99:1 dr, and >99% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74% yield, >99.9% ee, and 98:2 dr at a challenging substrate loading of 110 g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.
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Beyond traditional paper, multifunctional nanopaper has received much attention in recent years. Currently, many nanomaterials have been successfully used as building units of nanopaper. However, it remains a great challenge to prepare flexible and freestanding metal-organic framework (MOF) nanopaper owing to the low aspect ratio and brittleness of MOF nanocrystals. Herein, this work develops a flexible and free-standing MOF nanopaper with MOF nanowires as building units. The manganese-based MOF (Mn-MOF) nanowires with lengths up to 100 µm are synthesized by a facile solvothermal method. Through a paper-making technique, the Mn-MOF nanowires interweave with each other to form a three-dimensional architecture, thus creating a flexible and free-standing Mn-MOF nanowire paper. Furthermore, the surface properties can be engineered to obtain high hydrophobicity by modifying polydimethylsiloxane (PDMS) on the surfaces of the Mn-MOF nanowire paper. The water contact angle reaches 130°. As a proof of concept, this work presents two potential applications of the Mn-MOF/PDMS nanowire paper: (i) The as-prepared Mn-MOF/PDMS nanowire paper is compatible with a commercial printer. The as-printed colorful patterns are of high quality, and (ii) benefiting from the highly hydrophobic surfaces, the Mn-MOF/PDMS nanowire paper is able to efficiently separate oil from water.
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Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.
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Desinfectantes , Desinfección , Desinfección/métodos , Matriz Extracelular de Sustancias Poliméricas , Desinfectantes/farmacología , Cloro/farmacología , CinéticaRESUMEN
To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens (PCIOL) by a single suture. Nine eyes of nine patients were studied from September 2021 to March 2023. All patients had undergone vitrectomy. Only a single 9-0 polypropylene suture was used for scleral fixation. The three looped haptics were fixed at 12, 4, and 8 o'clock with six-point scleral fixation. The entire procedure took about 30 min. Among the nine patients, eight (88.8%) eyes had a significant improvement in best-corrected visual acuity, whereas one (11.2%) eye showed no change. No intraoperative or postoperative complications were observed. By ultrasonic biomicroscopy examination, intraocular lenses were well positioned and stable with no tilt in the horizontal and vertical axis. The method of six-point scleral fixation of a three-looped haptics PCIOL by a single suture is safe and effective.
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Implantación de Lentes Intraoculares , Lentes Intraoculares , Humanos , Implantación de Lentes Intraoculares/métodos , Tecnología Háptica , Técnicas de Sutura , Agudeza Visual , Esclerótica/cirugía , Suturas , Estudios RetrospectivosRESUMEN
When primary angle-closure glaucoma occurs during an acute attack, routine phacoemulsification is challenging because of the high intra-ocular pressure (IOP) and shallow anterior chamber (AC). To reduce IOP and deepen the AC before phacoemulsification, a portion of the vitreous body is often removed. In this report, we introduce an extended trocar/cannula system with lateral micropores to drain the liquid vitreous before routine phacoemulsification to solve this problem. A modified trocar was used to drain the liquefied vitreous before routine phacoemulsification. We demonstrated that this novel trocar/cannula system is safe and effective for draining liquefied vitreous before routine phacoemulsification. It also facilitates the transition to smooth phacoemulsification.
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Glaucoma de Ángulo Cerrado , Glaucoma , Facoemulsificación , Humanos , Cuerpo Vítreo/cirugía , Cánula , Drenaje , Presión Intraocular , Glaucoma de Ángulo Cerrado/cirugíaRESUMEN
BACKGROUND: Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively. RESULTS: A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients' ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis. CONCLUSION: In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.
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Isquemia Encefálica , Embolia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Lactante , Fibrinolíticos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Isquemia Encefálica/tratamiento farmacológico , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Hemorragias Intracraneales , Infarto Cerebral , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aimed to confirm that G protein-coupled estrogen receptor 1 (GPER1) deficiency affects cognitive function by reducing hippocampal neurogenesis via the PKA/ERK/IGF-I signaling pathway in mice with schizophrenia (SZ). METHODS: Mice were divided into four groups, namely, KO Con, WT Con, KO Con, and WT SZ (n = 12 in each group). All mice were accustomed to the behavioral equipment overnight in the testing service room. The experimental conditions were consistent with those in the animal house. Forced swimming test and Y-maze test were conducted. Neuronal differentiation and maturation were detected using immunofluorescence and confocal imaging. The protein in the PKA/ERK/IGF-I signaling pathway was tested using Western blot analysis. RESULTS: GPER1 KO aggravated depression during forced swimming test and decreased cognitive ability during Y-maze test in the mouse model of dizocilpine maleate (MK-801)-induced SZ. Immunofluorescence and confocal imaging results demonstrated that GPER1 knockout reduced adult hippocampal dentate gyrus neurogenesis. Furthermore, GPER1-KO aggravated the hippocampal damage induced by MK-801 in mice through the PKA/ERK/IGF-I signaling pathway. CONCLUSIONS: GPER1 deficiency reduced adult hippocampal neurogenesis and neuron survival by regulating the PKA/ERK/IGF-I signaling pathway in the MK-801-induced mouse model of SZ.
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Receptor alfa de Estrógeno , Hipocampo , Neurogénesis , Esquizofrenia , Animales , Ratones , Maleato de Dizocilpina/metabolismo , Maleato de Dizocilpina/farmacología , Receptor alfa de Estrógeno/genética , Proteínas de Unión al GTP/metabolismo , Hipocampo/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Neurogénesis/genética , Esquizofrenia/genéticaRESUMEN
Background: Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD). Methods: Six NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed. Results: A total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890). Conclusions: In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.
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Cobalt-based catalysts are ideal for CO2 reduction reaction (CO2RR) due to the strong binding and efficient activation of CO2 molecules on cobalt. However, cobalt-based catalysts also show low free energy of hydrogen evolution reaction (HER), making HER competitive with CO2RR. Therefore, how to improve the product selectivity of CO2RR while maintaining the catalytic efficiency is a great challenge. Here, this work demonstrates the critical roles of the rare earth (RE) compounds (Er2O3 and ErF3) in regulating the activity and selectivity of CO2RR on cobalt. It is found that the RE compounds not only promote charge transfer but also mediate the reaction paths of CO2RR and HER. Density functional theory calculations verify that the RE compounds lower the energy barrier of *CO â CO conversion. On the other hand, the RE compounds increase the free energy of HER, which leads to the suppression of HER. As a result, the RE compounds (Er2O3 and ErF3) improve the CO selectivity of cobalt from 48.8 to 69.6%, as well as significantly increase the turnover number by a factor of over 10.
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Background: Free-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China. Methods: We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions. Results: After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated. Conclusions: This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.
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The synthesis of structurally diverse amines is of fundamental significance in the pharmaceutical industry due to the ubiquitous presence of amine motifs in biologically active molecules. Biocatalytic reductive amination for amine production has attracted great interest owing to its synthetic advantages. Herein, we report the direct synthesis of a wide range of sterically demanding secondary amines, including several important active pharmaceutical ingredients and pharmaceutical intermediates, via reductive amination of carbonyl substrates and bulky amine nucleophiles employing imine reductases. Key to success for this route is the identification of an imine reductase from Penicillium camemberti with unusual substrate specificity and its further engineering, which empowered the accommodation of a broad range of sterically demanding amine nucleophiles encompassing linear alkyl and (hetero)aromatic (oxy)alkyl substituents and the formation of final amine products with up to >99% conversion. The practical utility of the biocatalytic route has been demonstrated by its application in the preparative synthesis of the anti-hyperparathyroidism drug cinacalcet.
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OBJECTIVES: This study was initiated to establish a renal thrombotic microangiopathy (TMA) scoring system based on clinical needs and investigate its predictive value for patients' long-term outcomes. METHODS: Kidney biopsy-proven Complement-mediated TMA (C-TMA) patients from January 2000 to December 2017 in Peking University First Hospital were retrospectively studied. Both acute and chronic TMA-related lesions, including 15 pathologic indices, were semiquantitatively scored. The interobserver and intraobserver reproducibility and correlation between the pathologic indices and clinical parameters were analyzed. Furthermore, the patients were divided into 2 groups by dialysis use at baseline, and the association of these pathologic indices with their prognostic outcomes was assessed between the two groups. RESULTS: Ninety-two patients with renal biopsy-proven C-TMA were enrolled. All fifteen included pathology indices showed good or moderate interobserver and intraobserver reproducibility and correlated well with several clinical parameters. Several clinicopathological indices were worse in the dialysis group than in the nondialysis group, such as serum creatinine, hemoglobin, platelet count, and estimated glomerular filtration rate. Moreover, morphologic features in the dialysis group presented with more severe vascular lesions. Interstitial fibrosis and chronic tubulointerstitial lesions were related to a trend of high risk of continuous dialysis in the dialysis group. Based on univariate and multivariable Cox regression analysis, more severe glomerular lesions, including glomerular mesangiolysis, glomerular basement membrane double contours and glomerular mesangial proliferation, were identified as risk factors predicting worse prognosis. CONCLUSIONS: Our renal C-TMA semiquantitative scoring system is reliable with good reproducibility and prognostic value in clinical practice, which needs further validation.
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Enfermedades Renales , Microangiopatías Trombóticas , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Microangiopatías Trombóticas/complicaciones , Microangiopatías Trombóticas/patología , Pronóstico , Diálisis Renal/efectos adversos , Enfermedades Renales/complicacionesRESUMEN
The current study was initiated to comprehensively evaluate renal NLRP3 inflammasome pathway activation in lupus nephritis (LN) patients and their clinicopathological significances based on a Chinese LN cohort. We found that the expressions of NLRP3, ASC, caspase-1, IL-1ß and IL-18 were all significantly higher in the kidneys of LN patients and were predominantly expressed in glomerular mesangial cells, podocytes, renal tubular epithelial cells and macrophages. The expressions of NLRP3, ASC, caspase-1 and IL-1ß were positively correlated to SLEDAI scores and several renal pathological activity indices, while the expression of NLRP3 was negatively associated with chronicity scores. Moreover, the foot process width was positively correlated with glomerular caspase-1 levels, and several podocyte injury markers were decreased significantly in LN patients with higher caspase-1 expression compared with those with lower expression. Our findings indicated that renal NLRP3 inflammasome was activated in LN patients and correlated with disease activity, which needs further explorations.
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Nefritis Lúpica , Humanos , Nefritis Lúpica/patología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Riñón/patología , Caspasa 1/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Non-ergot dopamine agonists (NEDAs) have been used as an adjunct therapy to levodopa in advanced Parkinson's disease (PD) for many years. However, there is no strong evidence that a given NEDA is more potent than another. To compare and rank the efficacy, tolerability, and safety of six commonly used NEDAs as an adjunct to levodopa in advanced PD, which includes long-acting and standard formulations, a network meta-analysis was performed. METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases were searched from January 1996 to June 2022 for eligible randomized controlled trials (RCTs). Six NEDAs, including rotigotine transdermal patch, ropinirole immediate-release (IR)/prolonged-release (PR), pramipexole IR/extended-release (ER), and piribedil, were investigated. RESULTS: A total of 34 RCTs (7868 patients) were included in the current study. The surface under the cumulative ranking curve indicated that ropinirole PR was associated with the best improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, and UPDRS-II + III (0.811, 0.742, and 0.827). For OFF time reduction, pramipexole IR ranked first (0.979), and ropinirole PR ranked first in OFF time responder rate (0.927). Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs). CONCLUSIONS: This network meta-analysis suggests six commonly used NEDAs are effective as an adjunct to levodopa in advanced PD. In comprehensive consideration of better symptomatic management, ropinirole PR may be a better choice than other NEDAs in advanced PD. Six NEDAs showed different profiles of AEs.
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Agonistas de Dopamina , Enfermedad de Parkinson , Humanos , Agonistas de Dopamina/efectos adversos , Levodopa/efectos adversos , Pramipexol , Enfermedad de Parkinson/tratamiento farmacológico , Dopamina , Metaanálisis en Red , Antiparkinsonianos/efectos adversosRESUMEN
Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet-Spengler (P-S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahydroisoquinoline alkaloids has attracted increasing attention due to their antitumor and antivirus activities. Herein, the L68T/M97V mutant of NCS from Thalictrum flavum with improved activity was developed by semi-rational design. This mutant not only showed higher catalytic performance (> 96% conversion) toward benzaldehyde and dopamine over the wild-type enzyme, but also catalysed the P-S reaction of the bulky substrate 4-biphenylaldehyde and dopamine with high conversion (> 99%) for the effective synthesis of 1-aryl-THIQA. In terms of stereoselectivity, all products synthesised by the L68T/M97V mutant showed high optical purity (92-99% enantiomeric excess).
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(+)-Neomenthylamine is an important industrial precursor used to synthesize high value-added chemicals. Here, we report a novel biocatalytic route to synthesize (+)-neomenthylamine by amination of readily available (-)-menthone substrate using ω-transaminase. By screening a panel of ω-transaminases, an ω-transaminase from Vibrio fluvialis JS17 was identified with considerable amination activity to (-)-menthone, and then characterization of enzymatic properties was conducted for the enzyme. Under optimized conditions, 10 mM (-)-menthone was transformed in a mild aqueous phase with 4.7 mM product yielded in 24 h. The biocatalytic route using inexpensive starting materials (ketone substrate and amino donor) and mild reaction conditions represents an easy and green approach for (+)-neomenthylamine synthesis. This method underscores the potential of biocatalysts in the synthesis of unnatural terpenoid amine derivatives.
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AIM: To observe the long-term clinical efficacy of intravitreal injections of conbercept, a novel vascular growth factor inhibitor, for the treatment of pathological myopia choroidal neovascularization (PM-CNV). METHODS: A total of 67 eyes (from 67 patients; mean age, 54.90±12.7y) with PM-CNV were retrospectively researched. Based on the different schemes used for the administration of the drug, the patients were divided into two groups: group A (n=35; average age, 53.31±13.6y; average diopter, 9.25±1.72 D), which received only one injection of pro re nata (PRN; 1+PRN regimen), and group B (n=32; average age, 56.49±11.8y; average diopter, 9.63±2.24 D), which received one injection per month for 3mo (3+PRN regimen). Best-corrected visual acuity (BCVA) analysis, intraocular pressure (IOP) examination, slit-lamp microscopy, fundus examination and optical coherence tomography were performed at each follow-up. The recurrence and treatment times of CNV were recorded. The patients were followed up for at least 12mo. RESULTS: The BCVA was increased in 29 eyes (82.9%) in group A and 30 eyes (93.75%) in group B; no increase or decrease was observed in 6 (17.1%) and 2 (6.25%) eyes in groups A and B, respectively. The BCVA (logMAR) values before treatment (0.67±0.48 and 0.71±0.56) were significantly higher than those 12mo after treatment (0.31±0.26 and 0.33±0.17) in groups A and B, respectively (P<0.05). The mean central macular thickness (CMT) values had significantly decreased from 346.49±65.99 and 360.10±82.31 µm at baseline to 257.29±40.47 and 251.97±48.26 µm in groups A and B, respectively, after 12mo of treatment. A total of 21 eyes in group A needed reinjection (60%; average number of injections, 2.51±0.98); the corresponding values in group B were 6 eyes (18.75%; average number of injections, 3.74±1.22). There were no adverse ocular and systemic complications during the treatment and follow-up. CONCLUSION: Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity, reduce macular edema and reduce the level of CMT in patients with PM-CNV. The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen, but requires more treatment. However, both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.
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Purpose: We aim to analyze the clinical and genetic features in a Chinese family with congenital retinoschisis by whole-exome sequencing and comprehensive clinical examination. Methods: Six members were recruited from a Chinese family. Three of them were diagnosed as congenital retinoschisis, including two twin siblings. All subjects received a full eye examination. Whole-exome sequencing (WES) and Sanger sequencing were performed on two twin probands and all participants, respectively. Results: A novel splice site mutation RS1.c.53-1G>A was identified in a Chinese congenital retinoschisis family. The mean onset age was 16.7 ± 2.4 years old. The average BCVA in patients was 0.37 ± 0.05. A typical spoke-wheel pattern was observed in all affected eyes. OCT examination results showed fovea schisis and schisis cavities were located in the inner nuclear layer in 100% eyes (6/6). ERG b/a ratio was decreased markedly, but was still more than 1 in the four eyes that were available. Conclusion: The present study discovered a new pathogenic splice cite variant of RS1 in congenital retinoschisis, which expands the mutational spectrum. In contrast to previous research, the phenotype of patients with the same mutation within one family was highly similar. Early molecular testing is crucial for early diagnosis, clinical management, and genetic counseling of patients with congenital retinoschisis.
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Epimedii Folium possesses many pharmacological activities including immunomodulation, anti-oxidation, and anti-tumor. Polysaccharides are the main components of Epimedii Folium, and their activities are closely related to the structure. The present study isolated a neutral polysaccharide(EPS-1-1) and an acidic polysaccharide(EPS-2-1) from the aqueous extract of Epimedii Folium through DEAE-52 cellulose anion-exchange chromatography and Sephadex G-100. The structures were characterized by chemical composition analysis, high-performance gel permeation chromatography(HPGPC), Fourier-transform infrared spectrometry(FT-IR), 1-phenyl-3-methyl-5-pyrazolone(PMP) derivatization, scanning electron microscopy(SEM), Congo red test, etc. The immunomodulatory activity of polysaccharides in vitro was determined by investigating the effects on the maturation of bone marrow-derived dendritic cells(BMDCs) and the release of inflammatory cytokines. According to the structural characterization analysis, EPS-1-1 was composed of fructose(Fuc), mannose(Man), ribose(Rib), rhamnose(Rha), glucose(Glc), galactose(Gal), xylose(Xyl), and arabinose(Ara) at 1.90â¶0.67â¶0.05â¶0.08â¶3.29â¶1.51â¶0.05â¶0.37(molar ratio), while EPS-2-1 was mainly composed of Fuc, Man, Rha, glucuronic acid(GlcA), galacturonic acid(GalA), Glc, Gal, Xyl, and Ara at 5.25â¶0.18â¶0.32â¶0.13â¶1.14â¶0.16â¶0.55â¶0.08â¶0.2. EPS-1-1 and EPS-2-1 could promote the maturation and function of BMDCs through up-regulating the expression of MHC-â ¡, CD86, CD80, and CD40, and increasing the levels of inflammatory cytokines(IL-6, IL-12, and TNF-α) in vitro experiments, which suggested that EPS-1-1 and EPS-2-1 possessed good immunomodulatory activity.