Reendothelialization of Acellular Adipose Flaps under Mimetic Physiological Dynamic Conditions.

The extensive soft-tissue defects resulting from trauma and tumors pose a prevalent challenge in clinical practice, characterized by a high incidence rate. Autologous tissue flap transplantation, considered the gold standard for treatment, is associated with various drawbacks, including the sacrifice of donor sources, postoperative complications, and limitations in surgical techniques, thereby impeding its widespread applicability. The emergence of tissue-engineered skin flaps, notably the acellular adipose flap (AAF), offers potential alternative solutions. However, a critical concern confronting large-scale tissue-engineered skin flaps currently revolves around the reendothelialization of internal vascular networks. In our study, we have developed an AAF utilizing perfusion decellularization, demonstrating excellent physical properties. Cytocompatibility experiments have confirmed its cellular safety, and cell adhesion experiments have revealed spatial specificity in facilitating endothelial cells adhesion within the adipose flap scaffold. Using a novel mimetic physiological fluid shear stress setting, endothelial cells were dynamically inoculated and cultured within the acellular vascular network of the pedicled AAF in our research. Histological and gene expression analyses have shown that the mimetic physiological fluid dynamic model significantly enhanced the reendothelialization of the AAF. This innovative platform of acellular adipose biomaterials combined with hydrodynamics may offer valuable insights for the design and manufacturing of 3D vascularized tissue constructs, which can be applied to the repair of extensive soft-tissue defects.

Imaging Artifacts and Quality Evaluation with Ultrawide-Field Swept-Source OCTA in Diabetic Retinopathy.

PURPOSE: To evaluate the prevalence and types of artifacts in ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA) scans of diabetic retinopathy (DR) patients. METHODS: This study was a prospective, observational study conducted from May 2022 to October 2022. Participants comprised individuals with proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), no diabetic retinopathy, and healthy controls. SS-OCTA imaging was performed, and a 5-scan composite with a larger field of view (23.5 mm × 17.5 mm) was captured using built-in software. Two experienced ophthalmologists analyzed the images independently, and the image quality and artifact prevalence were recorded and analyzed. RESULTS: The study included 70 eyes (16 with PDR, 24 with NPDR, 12 eyes of diabetic patients without DR, and 18 healthy eyes) in 70 subjects. Imaging artifacts were observed in a high percentage of eyes, with 98.57% of eyes presenting at least one type of artifact. A significant proportion of eyes (58.57%) exhibited a severe degree of artifacts. The most prevalent artifacts were loss of signal in 63 eyes (90%) and displacement artifact and masking artifact in 43 eyes (61.4%). Patients with more severe stages of DR had higher artifact scores (p < 0.05). Multivariate regression analysis indicated that DR severity was the most important factor influencing artifact scores (p < 0.05). CONCLUSIONS: In OCTA photos, various artifacts arise at different frequencies. It is crucial to qualitatively evaluate the images to ensure their quality. The results demonstrate that DR severity has a significant correlation with artifact scores.

Cytokine status and significant increase of IL-6 and sIL-6R in the aqueous humor of diabetic cataract patients revealed by quantitative multiplexed assays.

OBJECTIVE: This study aimed to investigate inflammatory cytokine expression profiles in the aqueous humor (AH) of diabetic cataract (DC) patients. METHODS: A quantitative multiplexed antibody assay was performed to measure the expression levels of 40 inflammatory cytokines in AH samples from DC and age-related cataract (ARC) patients. Bioinformatics analysis was used to examine the functions of the cytokines. Enzyme-linked immunosorbent assays (ELISAs) and western blots were performed to verify the data. RESULTS: The multiplexed antibody assay revealed that the expression levels of IL-6, sIL-6R, IL-17A, IL-8, MCP-1, TNF-ß, RANTES, TIMP-1, and TIMP-2 were higher in the AH of DC patients compared with ARC patients. However, IL-1ra and IL-1a expression levels were lower in the DC patient AH samples. Pathway analysis indicated that IL-6 and sIL-6R belong to the class I helical cytokine family, which is associated with many biological functions. ELISA and western blot results confirmed that IL-6R and IL-6 expression levels were significantly higher in DC patients compared with ARC patients. CONCLUSIONS: Our results revealed the status of 40 inflammatory cytokines in the AH by quantitative multiplexed assays. Additionally, IL-6 and sIL-6R were expressed markedly higher in DC compared with ARC, which may play critical roles in DC pathophysiology.

A peptidic network antibody inhibits both angiogenesis and inflammatory response.

Corneal neovascularization (CNV) is a global threat to human health. Traditional anti-angiogenesis agent may have therapy effect, while the inflammation in disease area remains unsolved. Herein, we reported two binding-induced fibrillogenesis (BIF) peptides as peptidic network antibodies for high-efficient and long-lasting anti-angiogenesis with reduced inflammatory response. BIF peptides could self-assemble into nanoparticles and further perform BIF behavior through binding Ca2+. In vitro, the migration of integrin αvß3 highly expressed endothelial cells was inhibited by BIF peptides. In vivo, one BIF peptide (0.012 mg/Kg) exhibited higher anti-angiogenesis effect than monoclonal antibody bevacizumab (0.96 mg/Kg) in a CNV rabbit model on day 14, despite that the dose of BIF was only 1.3% of bevacizumab. Meanwhile, the inflammatory response, such as PI3 kinase/Akt pathway in CNV was successfully inhibited as well. The peptidic network antibody could block integrin αvß3 via a long-term retention mode, which led to long-term therapeutic effect. The study provides BIF peptides as promising therapeutic agents for both anti-angiogenesis and reduced inflammatory response.

Molecular Cage with Dual Outputs of Photochromism and Luminescence Both in Solution and the Solid State.

The rational design of stimuli-responsive materials requires a deep understanding of the structure-activity relationship. Herein, we proposed an intramolecular conformation-locking strategy─incorporating flexible tetraphenylethylene (TPE) luminogens into the rigid scaffold of a molecular cage─to produce a molecular photoswitch with dual outputs of luminescence and photochromism in solution and in the solid states at once. The molecular cage scaffold, which restricts the intramolecular rotations of the TPE moiety, not only helps to preserve the luminescence of TPE in a dilute solution but facilitates the reversible photochromism on account of the intramolecular cyclization/cycloreversion reactions. Furthermore, we demonstrate assorted applications of this multiresponsive molecular cage, e.g., photo-switchable patterning, anticounterfeiting, and selective vapochromism sensing.

LONG-TERM EVOLUTION OF MYOPIC RETINOSCHISIS WITH A DOME-SHAPED MACULA AND PREDICTORS OF PROGRESSION AND VISUAL PROGNOSIS.

PURPOSE: To study the long-term natural course of myopic retinoschisis (MRS) with a dome-shaped macula (DSM) and to identify the factors affecting its development and visual prognosis. METHODS: In this retrospective case series study, we followed 25 MRS eyes with a DSM and 68 MRS eyes without a DSM for at least two years and observed changes in optical coherence tomography morphologic features and best-corrected visual acuity. RESULTS: During the mean follow-up of 48.3 ± 13.24 months, the difference in the rate of MRS progression between the DSM and non-DSM groups was not significant ( P = 0.7462). In the DSM group, the patients whose MRS progressed were older and had a higher refractive error than those whose MRS was stable or improved ( P = 0.0301 and 0.0166, respectively). The patients whose DSM was located in the central fovea had a significantly higher progression rate than those whose DSM was located in the parafovea ( P = 0.0421). For all DSM eyes, BCVA did not decrease significantly in eyes with extrafoveal retinoschisis ( P = 0.2500), patients whose best-corrected visual acuity decreased more than two lines had a greater central foveal thickness initially than those whose best-corrected visual acuity decreased less than two lines during the follow-up period ( P = 0.0478). CONCLUSION: A DSM did not delay the progression of MRS. The development of MRS in DSM eyes was associated with age, myopic degree, and DSM location. A higher schisis cavity predicted visual deterioration, and a DSM protected visual function in extrafoveal MRS eyes during the follow-up period.

Wide-field swept-source OCTA in the assessment of retinal microvasculature in early-stage diabetic retinopathy.

BACKGROUND: To perform a quantitative analysis of retinal microvasculature in patients with early-stage diabetic retinopathy (DR) using wide-field swept-source optical coherence tomography angiography (SS-OCTA).  METHODS: One hundred nineteen eyes of 119 patents (67 eyes with no DR and 52 eyes with mild-moderate nonproliferative diabetic retinopathy (NPDR)) were enrolled in this observational and cross-sectional cohort study, and an age-matched group consisting of 39 eyes of 39 non-diabetic subjects were set as the control. Each participant underwent a full ophthalmic examination, including wide-field SS-OCTA imaging. On OCTA scans (12 mm * 12 mm), the mean perfusion area (PA) and vessel density (VD) were independently measured in all 16 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Linear regression analyses were conducted to evaluate the influences of PA. RESULTS: In the central ring, there were no significant differences in the average PA and VD among the groups. In the 3 mm radius, the PA and VD of the no DR and mild-moderate NPDR were significantly decreased compared with the control group in superior and inferior quadrants. In the wide-field scans (9 and 12 mm radius), there was no significant difference in average PA and VD between the groups in each sectors (p > 0.05). Regression analysis found that the effect of VD on PA was statistically different (b = 1.311, p < 0.001). CONCLUSION: Wide-field OCTA imaging is useful for evaluating peripheral capillary perfusion in eyes with early-stage DR. Decrease in PA and VD was greater in the S3 and I3 sectors, and reductions in PA and VD were uneven in wide-filed sectors (9 and 12 mm radius).

Peripapillary vessel density and retinal nerve fiber layer thickness changes in early diabetes retinopathy.

AIM: To perform a quantitative analysis of the peripapillary vessel density (VD) and retinal nerve fiber layer (RNFL) thickness changes in patients with early stage of diabetic retinopathy (DR). METHODS: In this case-control study, swept-source optical coherence tomography angiography (SS-OCTA) imaging was used to examine diabetic and age-matched healthy subjects. The optic disc HD 6×6 mm2 blood flow imaging scan mode was selected. Automatic software was used to measure the peripapillary VD, capillary vessel density (CVD), and RNLF in an optic nerve head (ONH) filed based on the Garway-Heath map. In addition, the correlation between peripapillary VD, CVD, and RNFL was further investigated. RESULTS: The cohort consisted of 32 healthy individuals and 72 patients with diabetes (34 eyes with no DR and 38 eyes with mild-moderate NPDR). Peripapillary VD decreased in the mild-moderate NPDR group compared to the control group in most regions (P<0.05). Peripapillary CVD and RNFL thickness were significantly lower in the mild-moderate NPDR group in the superior temporal (ST) quadrants (P=0.018, P=0.030). In the correlation analysis of each region, the RNFL thickness in the NS region was positively correlated with the peripapillary VD and CVD (r=0.233, P=0.05; r=0.288, P=0.015). In the TI region, the RNFL thickness was positively correlated with the peripapillary CVD (r=0.237, P=0.047). CONCLUSION: The measurement based on the ONH topographic map may be helpful in detecting functional and structural impairments in DR. The peripapillary VD, CVD and RNFL decrease in early DR, and the RNFL thickness altered in association with the CVD or/and VD in some regions.

Fatal community-acquired bloodstream infection caused by Klebsiella variicola: A case report.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) is an infective microorganism of worldwide concern because of its varied manifestations and life-threatening potential. Genetic analyses have revealed that subspecies of K. pneumoniae exhibit higher virulence and mortality. However, infections with Klebsiella subspecies are often misdiagnosed and underestimated in the clinic because of difficulties in distinguishing K. pneumoniae from its subspecies using routine tests. This case study reports the rapid and fatal effects of K. pneumoniae subspecies. CASE SUMMARY: A 52-year-old male patient was febrile and admitted to hospital. Examinations excluded viral and fungal causes along with mycoplasma/chlamydia and parasitic infections. Bacterial cultures revealed blood-borne K. pneumoniae sensitive to carbapenem antibiotics, although corresponding treatment failed to improve the patient's symptoms. His condition worsened and death occurred within 72 h of symptom onset from sepsis shock. Application of the PMseq-DNA Pro high throughput gene detection assay was implemented with results obtained after death showing a mixed infection of K. pneumoniae and Klebsiella variicola (K. variicola). Clinical evidence suggested that K. variicola rather than K. pneumoniae contributed to the patient's poor prognosis. CONCLUSION: This is the first case report to show patient death from Klebsiella subspecies infection within a short period of time. This case provides a timely reminder of the clinical hazards posed by Klebsiella subspecies and highlights the limitations of classical laboratory methods in guiding anti-infective therapies for complex cases. Moreover, this report serves as reference for physicians diagnosing similar diseases and provides a recommendation to employ early genetic detection to aid patient diagnosis and management.

[Effects of Organic Fertilizer Replacing Chemical Fertilizer on Organic Carbon Mineralization and Active Organic Carbon in Dryland Yellow Soil].

At present, the effect characteristics and mechanism of organic fertilizer replacing chemical fertilizer on organic carbon mineralization and active organic carbon in dryland yellow soil remain unclear. In order to explore the effect of organic fertilizer replacing chemical fertilizer on organic carbon mineralization and active organic carbon in dryland yellow soil, we used soil with no fertilization (CK), only chemical fertilizer (NP), 50% organic fertilizer replacing chemical fertilizer (1/2(NPM)), and 100% organic fertilizer replacing chemical fertilizer (M). We examined the indoor mineralization culture of organic carbon and explored the characteristics of soil organic carbon and the change in active organic carbon under the condition of organic fertilizer replacing chemical fertilizer. The results showed that organic fertilizer replacing chemical fertilizer increased soil pH, organic carbon (SOC), total nitrogen (TN), and C/N. During the culture period, the soil organic carbon mineralization rate of all treatments decreased sharply in the initial stage (2-4 days), decreased slightly in the middle stage (4-20 days), and tended to be stable in the last stage (20-60 days). After fertilization, the cumulative mineralization of soil organic carbon significantly increased by 7.9%-27.7%. Compared with that in the NP treatment, the cumulative mineralization of soil organic carbon decreased by 5.2% in the 1/2(NPM) treatment and increased by 12.2% in the 1/2(NPM) treatment. Before mineralization culture, the substitution of organic fertilizer for chemical fertilizer had no significant effect on soil recalcitrant organic carbon (ROC) but significantly increased the content of microbial biomass carbon (MBC). The content of dissolved organic carbon (DOC) was significantly increased in the 1/2(NPM) treatment and decreased in the M treatment. After 60 days of culture, the content of soil active organic carbon in all treatments decreased compared with the initial content, of which MBC decreased the most (30.6%-41.2%). The accumulated mineralization of organic carbon was significantly positively correlated with soil pH and SOC and significantly positively correlated with the initial value of MBC and the change value before and after culture. To summarize, 100% organic fertilizer replacing chemical fertilizer significantly promoted soil organic carbon mineralization and reduced soil organic carbon stability; 50% organic fertilizer replacing chemical fertilizer inhibited soil organic carbon mineralization, which was beneficial to soil sequestration and fertilization; and 50% organic fertilizer replacing chemical fertilizer significantly increased soil active organic carbon content, and MBC was used as the main carbon source in the process of soil organic carbon mineralization.

Optical coherence tomography angiography for the detection and evaluation of ptic disc neovascularization: a retrospective, observational study.

BACKGROUND: To assess and characterize neovascularization of the optic disc (NVD) using optical coherence tomography angiography (OCTA) and different OCTA-based methods. METHODS: This retrospective, observational study included patients who were suspected of having early PDR with no presence of clinically apparent neovascularization (NV) bur were clinically diagnosed with proliferative diabetic retinopathy (PDR), or severe NPDR. Patients underwent standard clinical examinations and OCTA imaging using a 6 × 6 montage scan. Two trained graders identified NVD using different imaging systems (ultra-widefield-colour fundus photography (UWF-CFP), OCT, OCTA and fluorescein angiography (FA)). Moreover, morphological classification of NVD was performed. The detection and morphological classification of NVD by different OCTA-based methods (B-scan OCTA, En-face OCTA, VRI Angio and VRI Structure) were compared. RESULTS: A total of 169 eyes (126 eyes with PDR and 43 eyes with severe NPDR) of 123 participants were included in this study. The detection rate of NVD was 34.91% by UWF-CFP compared with 59.76% by OCT, 59.76% by OCTA, and 62.72% by FA. After excluding 2 cases with epiretinal membranes, the NVD diagnosis detected by OCT was used as the standard. Among 99 eyes diagnosed with NVD by OCT, B-scan OCTA detected NVD with a sensitivity of 97.98%, which was higher than that by en face OCTA (80.81%), VRI Angio (65.66%), and VRI Structure (61.62%) (all P < 0.05). According to its characteristics on OCTA, NVD was divided into four types (12 cases of type I, 6 cases of type II, 39 cases of type III, and 42 cases of type IV). For type I, B-scan OCTA exhibited a higher diagnostic sensitivity than other methods (P < 0.05). For types II and IV, there were no statistically significant differences in the sensitivity of various methods between the two groups (P > 0.05). CONCLUSION: OCTA and different OCTA-based methods are significant to the diagnosis of NVD, and the diagnostic accuracy of different detection methods may be related to different types of NVD.

Sirt5-mediated desuccinylation of OPTN protects retinal ganglion cells from autophagic flux blockade in diabetic retinopathy.

Retinal neurodegeneration develops early in the course of diabetic retinopathy (DR), and our previous research showed that succinate accumulation results in retinal ganglion cells (RGCs) dysfunction in the retinas of rats with DR. Succinate can enhance lysine succinylation, but the succinylation of DR is not well understood. In this study, we investigated the role of the succinylome in DR and identified the key factor in this process. TMT labeling and LC-MS/MS analysis were combined to quantify the differentially succinylated proteins between vitreous humor (VH) samples from DR and non-DR patients. A total of 74 sites in 35 proteins were differentially succinylated between DR and non-DR vitreous humor samples, among which succinylation of the K108 site of optineurin (OPTN K108su) in the defense response was enriched by GO analysis based on the biological process category. Then, using a streptozotocin (STZ)-induced diabetic rat model, R28 cells and primary rat RGCs (rRGCs), we demonstrated that OPTN underwent lysine succinylation in the retinas of rats with DR and that OPTN K108su mediated autophagic flux blockade under high-glucose (HG) conditions. Sirt5 can desuccinylate OPTN K108su, thus protecting RGCs function from high glucose-induced RGCs autophagic flux blockade in the diabetic retina. Overall, desuccinylation of OPTN is an essential adaptive mechanism for ameliorating autophagic flux blockade in RGCs under DR conditions, and targeting the Sirt5-desuccK108-OPTN axis may thus open an avenue for therapeutic intervention in RCGs dysfunction.

Characteristics of ocular findings of patients with neuronal intranuclear inclusion disease.

PURPOSE: This study aimed to explore the ocular characteristics of neuronal intranuclear inclusion disease (NIID), caused by GGC repeat expansion in the NOTCH2NLC gene, combined with the systemic clinical manifestations, and propose early diagnostic features of NIID. METHODS: Six patients (12 eyes) were enrolled in this study. In vivo corneal confocal microscopy (IVCCM), fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), full-field electroretinography (ERG), and electromyography were performed. RESULTS: The average corneal nerve fiber density (CNFD) was 6.83 ± 4.96 number/mm2, and the corneal nerve fiber length (CNFL) was 6.76 ± 1.96 mm/mm2. The nerves were looser and more curved in affected individuals. Dendritic cells were observed in patients with NIID. Chorioretinal atrophy, hyper-AF spots, and outer retinal abnormalities were observed during FAF imaging and OCT examinations. In full-field ERGs, the amplitudes of the a-wave and b-wave reduced or extinguished over time. The compound muscle action potential and motor nerve conduction velocity of the left common peroneal nerve decreased substantially. CONCLUSION: The findings of IVCCM and retinal changes should be included in the diagnostic criteria for NIID. Corneal confocal characteristics may precede the systemic neurological manifestations and provide a clinical basis for the early treatment and staging of the disease. ClincalTrials.gov. Identifier: ChiCTR21000500227.

Achieving WHO's Goal for Reducing Cesarean Section Rate in a Chinese Hospital.

Background: To address the worldwide dramatically increased Cesarean section (CS) rate in the past decades, WHO has recommended the CS rate should not be higher than 10-15%. Whether it is achievable remains unknown. Methods: We collected the data of delivery from 2008 to 2017 in two typical regional hospitals in China: Longhua Hospital (national policies rigorously implemented) and Dongguan Hospital (national policies not rigorously implemented). We compared between the two hospitals the 10 years trend in annual rate of CS, standardized by age, education level, parity, and CS history, against the time of issuing relevant national, local, and hospital policies. Results: In 10 years, 42,441 women in Longhua and 36,935 women in Dongguan have given birth. China's first national policy on CS reduction was issued in 2010 and the formal relaxation of one-child policy was issued in 2015-2016. In Longhua, the standardized annual CS rate was around 35% in 2008-2009, which declined sharply since 2010 down to 13.1% in 2016 (p < 0.001) and then leveled off. In contrast, in Dongguan, the rate stayed around 25% at the beginning, increased to 36% in 2011, decreased sharply to 27% in 2012, and leveled off until 2015 (p < 0.001), and then bounced back to 35% in 2017. The proportion of women with the history of CS increased significantly in the two hospitals (both roughly from 6% before 2010 to 20% after 2015). Analyses stratified by modified Robson classification showed that CS rates reduced in all risk classes of delivery women in Longhua but only in the Robson class 2 group in Dongguan. Major complications did not differ by hospital. Conclusion: With vigorously implementing national policies at micro levels, the WHO-recommended CS rate could be achieved without increase in major complications.

Forensic Analysis of Sudden Death Associated with Sexual Activity.

OBJECTIVES: To analyze the characteristics of sudden death associated with sexual activity to provide recommendations for forensic identification. METHODS: A retrospective analysis was conducted on autopsy cases accepted by Forensic Identification Center of Huazhong University of Science and Technology from 1998 to 2018, and a total of 15 cases of sudden death associated with sexual activity were screened out. The general information, case data and pathological changes of 15 cases were collected to find the relationship between sexual activity and sudden death. RESULTS: The ratio of male to female was 1.5∶1. The average age of males was 50.1 years and that of females was 35.0 years. Coronary artery diseases and brain diseases accounted for most of the cases (12/15). Sexual partners were associated with locations of deaths and body dumping behaviors. CONCLUSIONS: Sudden death associated with sexual activity, although rare, may occur in people over 30 years old with pre-existing heart or brain diseases, which should be paid attention to in forensic practice.

A pyridine-Si-rhodamine-based near-infrared fluorescent probe for visualizing reactive oxygen species in living cells.

A lysosomal-targeted near infrared (NIR) fluorescent probe for reactive oxygen species (ROS) was developed with highly sensitive ability. The different responding activity toward H2O2, OH, and HClO were investigated. Meanwhile, the probe has been successfully applied in detecting and imaging reactive oxygen species both in cells and in vivo.

Forensic Analysis of Sudden Death Associated with Sexual Activity / 法医学杂志

OBJECTIVES@#To analyze the characteristics of sudden death associated with sexual activity to provide recommendations for forensic identification.@*METHODS@#A retrospective analysis was conducted on autopsy cases accepted by Forensic Identification Center of Huazhong University of Science and Technology from 1998 to 2018, and a total of 15 cases of sudden death associated with sexual activity were screened out. The general information, case data and pathological changes of 15 cases were collected to find the relationship between sexual activity and sudden death.@*RESULTS@#The ratio of male to female was 1.5∶1. The average age of males was 50.1 years and that of females was 35.0 years. Coronary artery diseases and brain diseases accounted for most of the cases (12/15). Sexual partners were associated with locations of deaths and body dumping behaviors.@*CONCLUSIONS@#Sudden death associated with sexual activity, although rare, may occur in people over 30 years old with pre-existing heart or brain diseases, which should be paid attention to in forensic practice.

Suprachoroidal gene transfer with nonviral nanoparticles.

Subretinal injections of viral vectors provide great benefits but have limited cargo capacity; they induce innate and adaptive immune responses, which may cause damage and preclude repeated injections; and they pose administration risks. As a new biotechnology, suprachoroidal injections of biodegradable nanoparticles (NPs) containing a reporter plasmid induce reporter expression in rat photoreceptors and RPE throughout the entire eye and maintain expression for at least 8 months. Multiple injections markedly increase expression. Suprachoroidal injection of NPs containing a VEGF expression plasmid caused severe subretinal neovascularization progressing to subretinal fibrosis, similar to what occurs in untreated patients with neovascular age-related macular degeneration, providing a new model and proof of concept for level and duration of expression. Suprachoroidal injection of NPs containing a VEGF-binding protein expression plasmid significantly suppressed VEGF-induced vascular leakage and neovascularization demonstrating therapeutic potential. These data suggest that nonviral NP suprachoroidal gene transfer may provide a noninvasive, repeatable alternative to subretinal injection of viral vectors.

Clinical Characteristics and Prognosis of 218 Patients With COVID-19: A Retrospective Study Based on Clinical Classification.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread worldwide. Methods: This was a retrospective case series involving 218 patients admitted to three tertiary hospitals in the Loudi, Shaoyang, and Xiangtan areas of China from January 21 to June 27, 2020, who were confirmed by RT-PCR to have SARS-CoV-2. The patients' clinical characteristics, laboratory results, treatments, and prognoses based on clinical classification were recorded. Poor outcome was defined as admission to an ICU, the use of mechanical ventilation, or death. Results: The patients were classified into four clinical groups based on disease severity, namely mild (10/218, 5%), moderate (146/218, 67%), severe (24/218, 11%), or critical (14/218, 6%); 24 (11%) asymptomatic cases were also included in the study. The most common symptoms were self-reported cough (162/218, 74%), fever (145/218, 67%), sputum production (99/218, 45%), and fatigue (77/218, 35%). Among the 218 patients, 192 (88%) received lopinavir/ritonavir and interferon-alpha inhalation, and 196 (90%) patients received traditional Chinese medicine. Among the severe and critical patients, 25 (11%) were admitted to an ICU with or without mechanical ventilation, and one patient died. The presence of diabetes [relative risk (RR), 3.0; 95% CI, 1.3-6.8; p = 0.007) or other comorbidities (RR, 5.9; 95% CI, 1.9-17.8; p = 0.002) was independently associated with poor outcome. To date, 20 (9%) patients have retested positive for SARS-CoV-2 RNA after recovering and being discharged. Conclusion: The majority of patients in this case series were clinically classified as having moderate COVID-19. Older patients tended to present with greater levels of clinical severity. The prognosis for patients who were elderly or had diabetes or other chronic comorbidities was relatively poor.