Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Population pharmacokinetics of daptomycin in critically ill patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. METHODS: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. RESULTS: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min. CONCLUSIONS: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.

Artificial intelligence for prediction of COVID-19 progression using CT imaging and clinical data.

OBJECTIVES: Early recognition of coronavirus disease 2019 (COVID-19) severity can guide patient management. However, it is challenging to predict when COVID-19 patients will progress to critical illness. This study aimed to develop an artificial intelligence system to predict future deterioration to critical illness in COVID-19 patients. METHODS: An artificial intelligence (AI) system in a time-to-event analysis framework was developed to integrate chest CT and clinical data for risk prediction of future deterioration to critical illness in patients with COVID-19. RESULTS: A multi-institutional international cohort of 1,051 patients with RT-PCR confirmed COVID-19 and chest CT was included in this study. Of them, 282 patients developed critical illness, which was defined as requiring ICU admission and/or mechanical ventilation and/or reaching death during their hospital stay. The AI system achieved a C-index of 0.80 for predicting individual COVID-19 patients' to critical illness. The AI system successfully stratified the patients into high-risk and low-risk groups with distinct progression risks (p < 0.0001). CONCLUSIONS: Using CT imaging and clinical data, the AI system successfully predicted time to critical illness for individual patients and identified patients with high risk. AI has the potential to accurately triage patients and facilitate personalized treatment. KEY POINT: • AI system can predict time to critical illness for patients with COVID-19 by using CT imaging and clinical data.

[Factors Affecting the Surgical Level of Major Amputations in Patients with Severe Diabetic Foot].

Objective: To investigate the main factors affecting the surgical level of major amputations in patients with severe diabetic foot. Methods: A case-control study was conducted to analyze the clinical data of severe diabetic foot patients who had major amputations and were admitted to the Intensive Care Unit (ICU), Air Force Hospital of PLA Eastern Theater Command between July 2020 and July 2022. According to their surgical level of amputation, patients were divided into transtibial amputation (TT) group and transfemoral amputation (TF) group. Correlation analysis was performed with the clinical data of the patients, and multivariate logistic regression was performed to screen for relevant factors affecting the surgical level of major amputation. Results: The data of 48 patients with major amputations were collected, including 15 patients in the TT group and 33 patients in the TF group. The proportion of patients who had cardiovascular and cerebrovascular complications in the TT group was lower than that in the TF group (26.67% [4/15] vs. 57.58% [19/33], P<0.05), the proportion of patients who had lower extremity arterial intervention history was higher in the TT group than that in the TF group (40% [6/15] vs. 9.09% [3/33], P<0.05), and the proportion of patients who had elevated creatinine level was lower in the TT group than that in the TF group (70.31±22.98 vs. 127.98±108.38, P<0.05). Moreover, the history of lower extremity arterial intervention may be an independent protective factor for determining the surgical level of major amputations (odds ratio [ OR]=0.15, 95% confidence interval [ CI]: 0.03-0.72, P=0.018). Conclusion: History of cardiovascular and cerebrovascular diseases, serum creatinine level and history of lower extremity arterial intervention are the main factors affecting the surgical level of major amputations in patients with severe diabetic foot, and the history of lower extremity arterial intervention may be an independent protective factor.

The microvesicle/CD36 complex triggers a prothrombotic phenotype in patients with non-valvular atrial fibrillation.

The mechanisms responsible for platelet activation, the prothrombotic state, in non-valvular atrial fibrillation (NVAF) are still obscure. Microvesicles (MVs) can transfer various messages to target cells and may be helpful for exploring the detailed mechanisms. We aimed to investigate the possible mechanisms by which proatherogenic factors of NVAF contribute to platelet activation. Two hundred and ten patients with NVAF were stratified as being at 'low to moderate risk' or 'high risk' for stroke according to the CHADS2 score. Levels of platelet-derived MVs (PMVs) and platelet activation were examined. CD36-positive or CD36-deficient human platelets were stimulated by MVs isolated from NVAF patients with or without various inhibitors in vitro. Levels of PMVs and platelet activation markers enhanced significantly in high-risk patients. The MVs isolated from plasma of NVAF patients bound to platelet CD36 and activated platelets by phosphorylating the mitogen-activated protein kinase 4/Jun N-terminal kinase 2 (MKK4/JNK2) pathways. However, CD36 deficiency protected against MV-induced activation of platelets. We reveal a possible mechanism of platelet activation in NVAF and suggest that the platelet CD36 might be an effective target in preventing the prothrombotic state in NVAF.

Artificial Intelligence Augmentation of Radiologist Performance in Distinguishing COVID-19 from Pneumonia of Other Origin at Chest CT.

Background Coronavirus disease 2019 (COVID-19) and pneumonia of other diseases share similar CT characteristics, which contributes to the challenges in differentiating them with high accuracy. Purpose To establish and evaluate an artificial intelligence (AI) system for differentiating COVID-19 and other pneumonia at chest CT and assessing radiologist performance without and with AI assistance. Materials and Methods A total of 521 patients with positive reverse transcription polymerase chain reaction results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals from January 2020 to April 2020. A total of 665 patients with non-COVID-19 pneumonia and definite evidence of pneumonia at chest CT were retrospectively selected from three hospitals between 2017 and 2019. To classify COVID-19 versus other pneumonia for each patient, abnormal CT slices were input into the EfficientNet B4 deep neural network architecture after lung segmentation, followed by a two-layer fully connected neural network to pool slices together. The final cohort of 1186 patients (132 583 CT slices) was divided into training, validation, and test sets in a 7:2:1 and equal ratio. Independent testing was performed by evaluating model performance in separate hospitals. Studies were blindly reviewed by six radiologists without and then with AI assistance. Results The final model achieved a test accuracy of 96% (95% confidence interval [CI]: 90%, 98%), a sensitivity of 95% (95% CI: 83%, 100%), and a specificity of 96% (95% CI: 88%, 99%) with area under the receiver operating characteristic curve of 0.95 and area under the precision-recall curve of 0.90. On independent testing, this model achieved an accuracy of 87% (95% CI: 82%, 90%), a sensitivity of 89% (95% CI: 81%, 94%), and a specificity of 86% (95% CI: 80%, 90%) with area under the receiver operating characteristic curve of 0.90 and area under the precision-recall curve of 0.87. Assisted by the probabilities of the model, the radiologists achieved a higher average test accuracy (90% vs 85%, Δ = 5, P < .001), sensitivity (88% vs 79%, Δ = 9, P < .001), and specificity (91% vs 88%, Δ = 3, P = .001). Conclusion Artificial intelligence assistance improved radiologists' performance in distinguishing coronavirus disease 2019 pneumonia from non-coronavirus disease 2019 pneumonia at chest CT. © RSNA, 2020 Online supplemental material is available for this article.

Nitrate Esters Alleviated Coronary Atherosclerosis Through Inhibition of NF-κB-Regulated Macrophage Polarization Shift in Epicardial Adipose Tissue.

Nitrate esters have been used in clinical practice for more than one century for the treatment of angina. Their clinical effectiveness is due to vasodilator activity in arteries through a method of delivering nitric oxide or a nitric oxide-like compound. Recently, an increasing numbers of functions of this molecule in biology and pathophysiology have been discovered. Macrophage polarization shift in epicardial adipose tissue (EAT) has been demonstrated to be correlated with the severity of coronary artery disease (CAD). In this study, we aimed to investigate whether nitrate esters could improve coronary atherosclerosis through inhibition of macrophage polarization shift in EAT. A case-control study enrolled 48 subjects in 2 groups: CAD patients with or without nitrate esters treatment. Infiltration of M1/M2 macrophages and the expressions of pro-inflammatory and anti-inflammatory cytokines in EAT and subcutaneous white adipose tissue were investigated by immunohistochemical stain among subjects undergoing coronary artery bypass graft surgery. The expression levels of metabolic genes were investigated by real-time reverse transcription-polymerase chain reaction (RT-PCR). We found that nitrate ester treatment significantly inhibited NF-кB activity and decreased macrophage infiltration and M1/M2 macrophage ratio in EAT in patients with CAD. The expressions of pro-inflammatory cytokines were significantly decreased, along with significantly elevated expressions of anti-inflammatory cytokines in CAD patients with nitrate ester treatment, corresponding EAT dysfunction was ameliorated and the severity of patients with CAD (Gensini score) was significantly decreased. The protective effects on macrophage polarization and EAT function through NF-кB activity inhibition suggested a potential mechanism of nitrate esters in alleviating the severity of CAD.

Suppression of isoproterenol-induced apoptosis in H9c2 cardiomyoblast cells by daidzein through activation of Akt.

Increased serum norepinephrine level is one of pathological processes relating to heart disease (HD). Estrogens are considered as potential therapeutics for the treatment of HD; however, estrogen supplementation shows some side-effects, such as increasing the risk of developing breast, endometrial and ovarian cancers. This study investigated the cardio-protective effects of daidzein (Dai), a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, H9c2 cells treated with Dai at different concentrations showed no statistical difference in cell viability. TdT-mediated digoxigenin-dUTP nick-end labeling (TUNEL) data and western blotting results indicated that Dai treated-H9c2 cells recovered from the damage induced by ISO. The recovery effects of Dai on ISO-induced damage were blocked by inhibition of Akt activation through adding Akt inhibitor. On the other hand, the fold changes of phosphorylated Akt (p-Akt)/Akt normalized with the control for con, 0.25, 0.5, 1, 3 and 24 h of treatment were 1, 2, 5, 13, 11 and 10, respectively. In conclusion, Dai ameliorates apoptosis of cardiomyoblasts induced by ISO through Akt signaling pathway.

Prostaglandin F2α receptor silencing attenuates vascular remodeling in rats with type 2 diabetes.

BACKGROUND: Vascular remodeling is an important feature of diabetic macrovascular complications. The prostaglandin F2α receptor (FP), the expression of which is upregulated by insulin resistance and diabetes, is reportedly involved in myocardial remodeling. In this study, we aimed to investigate whether the FP receptor is implicated in diabetes-induced vascular remodeling. METHODS: A type 2 diabetic rat model was induced through a high-fat diet and low-dose streptozotocin (STZ). Thirty-two rats were randomized into four groups: control, diabetes, diabetes treated with empty virus and diabetes treated with FP receptor-shRNA. Then, we evaluated the metabolic index, FP receptor expression and vascular remodeling. We used FP receptor gene silencing in vivo to investigate the role that the FP receptor plays in the pathophysiologic features of vascular remodeling. RESULTS: Diabetic rats displayed increased levels of blood glucose, cholesterol, and triglycerides, as well as severe insulin resistance and FP receptor overexpression. In addition, increased medial thickness, excessive collagen deposition and diminished elastic fibers were observed in the diabetic rats, resulting in vascular remodeling. In the FP receptor-shRNA group, the medial thickness, collagen content, elastin/collagen ratio, and collagen I/collagen III content ratio were markedly decreased. Additionally, with FP receptor gene silencing, the JNK phosphorylation level was markedly decreased. CONCLUSIONS: Silencing of the FP receptor exerts a protective effect on diabetes-induced vascular remodeling, thereby suggesting a new therapeutic target for vascular remodeling in diabetes.

[The use of music intervention in nursing practice for elderly dementia patients: a systematic review].

BACKGROUND: Although music therapy is now applied widely as an intervention for elderly dementia patients, the effectiveness of this therapy is not yet well understood. PURPOSE: This study conducts a systematic review of clinical studies that address the effectiveness of music therapy in elderly dementia patients. METHODS: Databases including MEDLINE, Cochrane Library, ProQuest, EBMR, CINAHL, and CEPS were searched for relevant articles published between 2004 and 2013 using the key words "music" or "music therapy" with "dementia". An initial 272 original articles were identified. Applying inclusion criteria and excluding duplications left 18 articles that used randomized controlled trials to assess the effectiveness of music therapy in elderly participants for further analysis and synthesis. RESULTS: Music therapy was found effective at improving cognitive functions, mental symptoms, and eating problems. However, this therapy was not found effective at improving irritable behavior. Type of music and method of presentation were the most important factors affecting results. Most studies (61.1%) used songs familiar to ÷ favored by the participants; most studies delivered 30-minute interventions twice weekly; and most studies used a therapy duration of 6 hours. Finally, most studies (77.8%) had music therapy sessions performed by either music therapists or trained healthcare providers. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study supports that music therapy is an effective nursing intervention for elderly dementia patients. The authors hope that findings are a helpful reference for clinical nurses to develop practical music therapy procedures and protocols.

Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar-/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8+ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8+ T cells declined but showed increased activation, while both the number and activation of effector memory CD4+ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80+/CD86+ B cells and resting memory B cells (CD27+CD21+) increased significantly. Intermediate monocytes (CD14+CD16+) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4+ T cells, B cells, CD16+CD56+ NK cells, CD14+CD16+ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

[Factors of influence on willingness to participate in the N3 nursing clinical ladder program].

BACKGROUND: The professional nursing clinical ladder program can effectively enhance the professional morale of nursing staff and help retain the best senior nurses in clinical settings. Hence, it is important to explore factors that influence nurse staff intentions to participate in the clinical ladder. PURPOSE: This study examined factors that affect nurse staff intention to participate in the N3 nurse clinical ladder program. METHODS: We used a cross sectional study design and a structured questionnaire survey. We employed purposive sampling to recruit 389 nurse staffs qualified for promotion to the N3 level from a medical center in southern Taiwan. RESULTS: Findings showed: (1) Nearly two-thirds (233, 59.9%) of participants intended to participate in clinical ladder; (2) The factors of age, years of nursing experience, years in current position, project/research experience, promotion experience, and intention all significantly affected intent to participate in the ladder; (3) A significant difference between willingness to participate in the ladder program and each of the following variables--motivation, satisfaction, professional capacity, and sense of achievement; (4) Logistic regression analysis identified only motivation as a valid predictor of willingness to participate the ladder program (95% CI: 1.21-3.78). CONCLUSION/IMPLICATIONS FOR PRACTICE: Results provide a useful reference to nursing administrators for planning on-the-job training and increasing nurse staff participation in the ladder. The authors hope results can help promote better human resource management and achievements.

Relationships between Willingness to Participate in the Nursing Clinical Ladder Program and Its Related Factors among Clinical Nurses.

The professional nursing competence ladder system can effectively inspire nurses' work morale, improve quality of life, and avoid the issue of senior staff leaving the clinical setting. The aim of this study was to explore the willingness to participate in the professional nursing competence ladder system and its related factors among nurses. A cross-sectional study design with a structured questionnaire was used. Purposive sampling was employed, and 696 nurses who qualified to be promoted as N2 were recruited from a medical center in southern Taiwan. The results showed most nurses were willing to participate in the nursing ladder system. There were significant differences between willingness to participate in the ladder system and age, education level, as well as promotion experience. This study emphasizes the importance of intensifying internal encouraging factors and strengthening external encouraging factors to improve participation rates. Healthcare institutions could provide instruction on case report writing to increase nurses' willingness to participate in the clinical ladder program.

Hydrosulfonylation of Alkenes with Sulfonyl Imines via Ir/Cu Dual Photoredox Catalysis.

Sulfonamides exhibit the advantages of wide prevalence, excellent prefunctionalization capability, and broad functional group compatibility. We report here utilizing sulfonyl imines as sulfonyl radical precursors for hydrosulfonylation of activated alkenes via visible-light irradiation. By preinstallation of functional groups into the sulfonamides and subsequent hydrosulfonylation, a variety of complex sulfones were synthesized with good efficiency under Ir/Cu dual photoredox catalysis. Additionally, this protocol expands the research in late-stage N-S bond modification in sulfonamides.

Visible-Light-Mediated Late-Stage Sulfonylation of Anilines with Sulfonamides.

A visible-light-mediated late-stage sulfonylation of anilines with sulfonamides under simple reaction conditions is presented. Various primary or secondary sulfonamides including several pharmaceuticals were incorporated successfully via N-S bond activation and C-H bond sulfonylation. The synthetic utility of this strategy is highlighted by the construction of complex anilines bearing diverse bioactive groups.

Successful treatment of metastatic vulvar malignant melanoma with toripalimab: A rare case report and review of the literature.

RATIONALE: Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma. PATIENT CONCERNS AND DIAGNOSES: A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy. INTERVENTIONS: The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane. OUTCOMES: After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety. LESSONS: In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab.

Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice.

Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model ( Tg-Twist1 iEC+ ). Whole-mount retinas from Tg-Twist1 iEC+ mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/ß-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a 'valve' in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.