Publications by authors named "Chong Guo"

66 Publications

Artificial intelligence manages congenital cataract with individualized prediction and telehealth computing.

NPJ Digit Med 2020 Aug 28;3(1):112. Epub 2020 Aug 28.

Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
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http://dx.doi.org/10.1038/s41746-020-00319-xDOI Listing
August 2020

MicroRNA-18a-5p regulates the Warburg effect by targeting hypoxia-inducible factor 1α in the K562/ADM cell line.

Exp Ther Med 2021 Oct 28;22(4):1069. Epub 2021 Jul 28.

Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

The Warburg effect is involved in drug resistance and recurrence of cancer, and poses a challenge for the treatment of chronic myelogenous leukemia (CML). Hypoxia-inducible factor 1α (HIF-1α) plays a key role in the Warburg effect. microRNAs (miRs) targeting HIF-1α have potential of regulating such aberrant metabolic process. The present study demonstrated that miR-18a-5p was expressed at a low level in K562/ADM cells via reverse transcription-quantitative PCR (RT-qPCR). The results of the luciferase reporter assay indicated that miR-18a-5p could specifically bind the 3'-untranslated region of HIF-1α. Through RT-qPCR and western blotting, it was revealed that miR-18a-5p downregulated the expression of HIF-1α. By inhibiting HIF-1α, miR-18a-5p suppressed aerobic glycolysis in K562/ADM cells, according to the results produced by glucose uptake, lactate production, pyruvate level and ATP synthesis measurement, along with the results obtained from extracellular acidification rate and oxygen consumption rate assays. These results provided new evidence that miR-18a-5p may suppress the Warburg effect by targeting HIF-1α. Furthermore, via CCK-8 and flow cytometry assays, cells transfected with miR-18a-5p mimics were more sensitive to Adriamycin (AMD) compared with AMD group. Reversing the Warburg effect by miR-30a-5p might provide a potential therapeutic strategy for CML.
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http://dx.doi.org/10.3892/etm.2021.10503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355681PMC
October 2021

The therapeutic value and molecular mechanisms of lncRNA FENDRR in human cancer.

Curr Pharm Des 2021 Aug 19. Epub 2021 Aug 19.

College of Medical Science, China Three Gorges University, Yichang. China.

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy.

Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed.

Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed.

Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.
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http://dx.doi.org/10.2174/1381612827666210820094702DOI Listing
August 2021

Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex.

Elife 2021 08 9;10. Epub 2021 Aug 9.

Department of Neurobiology, Harvard Medical School, Boston, United States.

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye movement. Here, we find a link between these specializations in mice: PCs preferentially inhibit metabotropic glutamate receptor type 1 (mGluR1)-expressing UBCs that respond to mossy fiber (MF) inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABA receptors (GABARs) and inhibit almost all mGluR1-expressing UBCs by activating GABA receptors (GABARs). PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. Based on optogenetic studies and a small number of paired recordings, GABAR-mediated feedback is fast and unreliable. GABAR-mediated inhibition is slower and is sufficiently large to strongly influence the input-output transformations of mGluR1-expressing UBCs.
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http://dx.doi.org/10.7554/eLife.68802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352585PMC
August 2021

Automated detection of retinal exudates and drusen in ultra-widefield fundus images based on deep learning.

Eye (Lond) 2021 Aug 3. Epub 2021 Aug 3.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Retinal exudates and/or drusen (RED) can be signs of many fundus diseases that can lead to irreversible vision loss. Early detection and treatment of these diseases are critical for improving vision prognosis. However, manual RED screening on a large scale is time-consuming and labour-intensive. Here, we aim to develop and assess a deep learning system for automated detection of RED using ultra-widefield fundus (UWF) images.

Methods: A total of 26,409 UWF images from 14,994 subjects were used to develop and evaluate the deep learning system. The Zhongshan Ophthalmic Center (ZOC) dataset was selected to compare the performance of the system to that of retina specialists in RED detection. The saliency map visualization technique was used to understand which areas in the UWF image had the most influence on our deep learning system when detecting RED.

Results: The system for RED detection achieved areas under the receiver operating characteristic curve of 0.994 (95% confidence interval [CI]: 0.991-0.996), 0.972 (95% CI: 0.957-0.984), and 0.988 (95% CI: 0.983-0.992) in three independent datasets. The performance of the system in the ZOC dataset was comparable to that of an experienced retina specialist. Regions of RED were highlighted by saliency maps in UWF images.

Conclusions: Our deep learning system is reliable in the automated detection of RED in UWF images. As a screening tool, our system may promote the early diagnosis and management of RED-related fundus diseases.
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http://dx.doi.org/10.1038/s41433-021-01715-7DOI Listing
August 2021

LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151-5p/WNT7A axis.

Pathol Res Pract 2021 Sep 21;225:153561. Epub 2021 Jul 21.

Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, China. Electronic address:

Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of human thyroid cancer (TC), including papillary thyroid carcinoma (PTC); PTC is the most common pathological subtype of TC. To date, the expression, function, and mechanism of the lncRNA CASC15 in PTC remain unclear. The present study results showed that CASC15 was overexpressed in PTC tissues compared with normal tissues and acted as a potent oncogene to promote the proliferation and tumorigenesis of PTC cells both in vitro and in vivo. Mechanistic studies demonstrated that CASC15 could serve as an endogenous miRNA sponge to absorb and downregulate miR-7151-5p, thereby preventing the inhibition of WNT7A during PTC progression. Furthermore, the study demonstrated that CASC15 activated the WNT/β‑catenin signaling pathway by upregulating WNT7A in PTC. Taken together, our findings identified CASC15 as a potential diagnostic marker or therapeutic target for PTC progression. DATA AVAILABILITY: Please contact the corresponding author for a data request.
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http://dx.doi.org/10.1016/j.prp.2021.153561DOI Listing
September 2021

DUXAP8: a promising lncRNA with carcinogenic potential in cancer.

Curr Med Chem 2021 Jul 25. Epub 2021 Jul 25.

College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: Long non-coding RNAs (lncRNA) have influenced numerous biology processes, which has provoked great interest. Not only that, LncRNA DUXAP8 mediates tumorigenesis by affecting the activity of miRNAs, signaling pathways, and oncogene.

Methods: The functions of DUXAP8 have been summarized by reading relevant articles on PubMed.

Results: lncRNA DUXAP8 acts oncogene in most tumors. The abnormal over-expression is associated with the proliferation, invasion, migration, anti-autophagy of tumors. DUXAP8 exerts promotion on Akt / mTOR signaling pathway, facilitating the occurrence of tumors. Furthermore, DUXAP8 affects the activity of miRNAs and proteins, showing its significant potential as a therapeutic target in human cancers.

Conclusion: LncRNA DUXAP8 has been identified as an indispensable therapeutic target of the tumors, providing clinical treatment plans.
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http://dx.doi.org/10.2174/0929867328666210726092020DOI Listing
July 2021

Endometrial Cancer: genetic, metabolic characteristics, therapeutic strategies and nanomedicine.

Curr Med Chem 2021 Jul 5. Epub 2021 Jul 5.

College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: Endometrial cancer is the fourth most common malignancy in the female population worldwide. It was estimated that 65,620 new cases and 12,590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments.

Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer.

Method: Relevant articles were retrieved from Pubmed and were systematically reviewed.

Results: Hypoxia-inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer, and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. The examination of the abnormal X chromosome inactivation may help with the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as immunotherapy. Nanotechnology showed great potential in endometrial cancer's early diagnosis, metastasis determination and treatment.

Conclusion: Endometrial cancer has been understood in various aspects, but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied, but the current researches showed great results in treating endometrial cancer. It needs further researching.
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http://dx.doi.org/10.2174/0929867328666210705144456DOI Listing
July 2021

The functional role of oncogenic lncRNA BCAR4 for cancer outcome.

Curr Pharm Des 2021 Jun 4. Epub 2021 Jun 4.

College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy.

Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed.

Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration.

Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.
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http://dx.doi.org/10.2174/1381612827666210604114955DOI Listing
June 2021

Molecular mechanism of the canonical oncogenic lncRNA MALAT1 in gastric cancer.

Curr Med Chem 2021 May 21. Epub 2021 May 21.

Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China.

Many experimental shreds of evidence have shown that lncRNA MALAT1 is related to proliferation ability, invasion and migration ability, autophagy ability, and chemoresistance in gastric cancer. Moreover, MALAT1 is related to metastasis and patient prognosis in gastric cancer. This review aims to reveal the biological functions and specific mechanisms of MALAT1 in gastric cancer.

Methods: After a comprehensive and systematic search in PubMed, various molecular mechanisms of MALAT1 in mediating gastric carcinogenesis are collated and summarized.

Results: MALAT1-mediated gastric cancer is involved in a variety of molecular mechanisms. For example, MALAT1 can enhance the proliferation ability of gastric cancer cells by inhibiting the expressions of miR-122, miR-1297, miR-22-3p, miR-202, etc. MALAT1 enhances the metastasis and invasion of gastric cancer by participating in EMT process, PI3-Akt and other pathways. MALAT1 enhances the proliferation and invasion of gastric cancer by inhibiting the function of tumor suppressor gene PCDH10. MALAT1 can increase the autophagy ability of gastric cancer cells by inhibiting miR-183 and increasing the level of autophagy markers. MALAT1 enhances chemical resistance by inhibiting UPF1 and miR-30e levels.

Conclusions: MALAT1 is tightly linked to gastric carcinogenesis through various molecular mechanisms. Moreover, MALAT1 is also closely associated with chemoresistance and poor prognosis in gastric cancer patients, suggesting the possibility of its use as a clinical therapeutic target and a promising independent risk factor for predicting patient prognosis.
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http://dx.doi.org/10.2174/0929867328666210521213352DOI Listing
May 2021

Rapid BMI Increases and Persistent Obesity in Small-for-Gestational-Age Infants.

Front Pediatr 2021 4;9:625853. Epub 2021 May 4.

Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

In order to compensate for the early intrauterine growth restriction, small-for-gestational age (SGA) infants have "catch-up growth" after birth. Increased caloric intake has been suggested for SGA infants conventionally. It is important to determine if the early growth rate of body mass index (BMI) is associated with risk of persistent obesity later in life. In this longitudinal cohort study, we assessed the BMI of a large cohort of children who were SGA at birth to determine their risk of persistent obesity at school age (6-7 years) due to excessive weight gain in the first 3 years of life. We collected the height and weight data of 23,871 SGA babies. A polynomial function was used to fit the BMI-for-age z-score (BAZ) values of 0-6 years old SGA children and interpolate their growth trajectory. In addition, we screened out 6,959 children from 23,871 children to further evaluate the dynamic changes of early childhood BMI. We divided the school-age children into groups as non-obese (BAZ < 2) and obese (BAZ > 2), and determined the association between changes in BMI and school-age obesity. From the perspective of BMI distribution, the interpolated growth trajectory indicated that SGA children reaching overweight status or developing obesity by 3 years of age, continued to have obesity until school age (R, 0.65; R, 0.21). The retrospective analysis showed that children who were overweight and had obesity during school age had a high BMI from early age. By analyzing the changes in early BMI, we found that the fastest growth of SGA children occurred in the early infancy before 6 months and they continued to grow rapidly for a period of time. Interestingly, former SGA children who maintained a near overweight (1 < BAZ < 2) status before the age of 2 maintained an appropriate growth rate and usually did not develop obesity. A rapid increase in BMI during early infancy in former SGA newborns leads to a persistent risk of obesity. The energy intake of SGA infants should appropriately meet the infants' growth needs and early BMI changes should be closely monitored for an optimal integrated management.
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http://dx.doi.org/10.3389/fped.2021.625853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129028PMC
May 2021

Real-world big data demonstrates prevalence trends and developmental patterns of myopia in China: a retrospective, multicenter study.

Ann Transl Med 2021 Apr;9(7):554

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Myopia is a complex disease caused by a combination of multiple pathogenic factors. Prevalence trends and developmental patterns of myopia exhibit substantial variability that cannot be clearly assessed using limited sample sizes. This study aims to determine the myopia prevalence over the past 60 years and trace the myopia development in a school-aged population using medical big data.

Methods: The refraction data from electronic medical records in eight hospitals in South China were collected from January 2005 to October 2018; including patients' year of birth, refraction status, and age at the exam. All optometry tests were performed in accordance with standard procedures by qualified senior optometrists. The cross-sectional datasets (individuals with a single examination) and longitudinal datasets (individuals with multiple examinations) were analyzed respectively. SAS statistical software was used to extract and statistically analyse all target data and to identify prevalence trends and developmental patterns related to myopia.

Results: In total, 1,112,054 cross-sectional individual refraction records and 774,645 longitudinal records of 273,006 individuals were collected. The myopia prevalence significantly increased among individuals who were born after the 1960s and showed a steep rise until reaching a peak of 80% at the 1980s. Regarding developmental patterns, the cross-sectional data demonstrated that the myopia prevalence increased dramatically from 23.13% to 82.83% aging from 5 to 11, and the prevalence stabilized at the age of 20. The longitudinal data confirmed the results that the age of myopic onset was 7.47±1.67 years, the age of myopia stabilized at 17.14±2.61 years, and the degree of myopia stabilized at -4.35±3.81 D.

Conclusions: The medical big data used in this study demonstrated prevalence trends of myopia over the past 60 years and revealed developmental patterns in the onset, progression and stability of myopia in China.
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http://dx.doi.org/10.21037/atm-20-6663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105816PMC
April 2021

Flower Development of Heterodichogamous (Juglandaceae).

Front Plant Sci 2021 30;12:541163. Epub 2021 Mar 30.

College of Forestry, Shenyang Agricultural University, Shenyang, China.

is a monoecious heterodichogamous species with protogynous and protandrous mating strategies that occur at a 1:1 ratio and are randomly distributed in the population. The inconsistent male and female flowering periods of the same mating type result in an imbalance of the ratio of male and female flowers, contributing to the low yield of this species. However, little more is known about its floral development. Following three consecutive years of observations, histological analysis, and scanning electron microscopy, we found that the morphological and anatomical development of the male and female flowers were synchronous. The male floral morphological development of . was divided into seven phases, while that of the female flower was nine. Four stages were shared between the male and female flower's anatomical development. Our findings indicate that there was minimal overlap between sexual functions within the same mating type, guaranteeing synchronization, mutual non-interference, outcrossing, and avoidance of self-fertilization. These results provide a theoretical basis for the improvement of fruit yield and quality through the reasonable allocation of protogynous and protandrous individuals in a population, and for artificial pollination control. Further, these findings lay a foundation for further research on the genetic mechanisms and environmental effects on flower development of heterodichogamous . .
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http://dx.doi.org/10.3389/fpls.2021.541163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042317PMC
March 2021

An artificial intelligence platform for the diagnosis and surgical planning of strabismus using corneal light-reflection photos.

Ann Transl Med 2021 Mar;9(5):374

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Background: Strabismus affects approximately 0.8-6.8% of the world's population and can lead to abnormal visual function. However, Strabismus screening and measurement are laborious and require professional training. This study aimed to develop an artificial intelligence (AI) platform based on corneal light-reflection photos for the diagnosis of strabismus and to provide preoperative advice.

Methods: An AI platform consisting of three deep learning (DL) systems for strabismus diagnosis, angle evaluation, and operation plannings based on corneal light-reflection photos was trained and retrospectively validated using a retrospective development data set obtained between Jan 1, 2014, and Dec 31, 2018. Corneal light-reflection photos were collected to train the DL systems for strabismus screening and deviation evaluations in the horizontal strabismus while concatenated images (each composed of two photos representing different gaze states) were procured to train the DL system for operative advice regarding exotropia. The AI platform was further prospectively validated using a prospective development data set captured between Sep 1, 2019, and Jun 10, 2020.

Results: In total, 5,797 and 571 photos were included in the retrospective and prospectively development data sets, respectively. In the retrospective test sets, the screening system detected strabismus with a sensitivity of 99.1% [95% confidence interval (95% CI), 98.1-99.7%], a specificity of 98.3% (95% CI, 94.6-99.5%), and an AUC of 0.998 (95% CI, 0.993-1.000, P<0.001). Compared to the angle measured by the perimeter arc, the deviation evaluation system achieved a level of accuracy of ±6.6º (95% LoA) with a small bias of 1.0º. Compared to the real design, the operation advice system provided advice regarding the target angle within ±5.5º (95% LoA). Regarding strabismus in the prospective test set, the AUC was 0.980. The platform achieved a level of accuracy of ±7.0º (95% LoA) in the deviation evaluation and ±6.1º (95% LoA) in the target angle suggestion.

Conclusions: The AI platform based on corneal light-reflection photos can provide reliable references for strabismus diagnosis, angle evaluation, and surgical plannings.
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http://dx.doi.org/10.21037/atm-20-5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033395PMC
March 2021

ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis.

Curr Pharm Des 2021 ;27(23):2722-2727

College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways, such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers.

Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively.

Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, and inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, and regulating miRNAs and proteins, shows its significant potential as a therapeutic cancer target.

Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.
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http://dx.doi.org/10.2174/1381612827666210325105106DOI Listing
January 2021

Predicting subretinal fluid absorption with machine learning in patients with central serous chorioretinopathy.

Ann Transl Med 2021 Feb;9(3):242

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.

Background: Machine learning was used to predict subretinal fluid absorption (SFA) at 1, 3 and 6 months after laser treatment in patients with central serous chorioretinopathy (CSC).

Methods: The clinical and imaging data from 480 eyes of 461 patients with CSC were collected at Zhongshan Ophthalmic Center (ZOC) and Xiamen Eye Center (XEC). The data included clinical features from electronic medical records and measured features from fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography angiography (OCTA), and optical coherence tomography (OCT). A ZOC dataset was used for training and internal validation. An XEC dataset was used for external validation. Six machine learning algorithms and a blending algorithm were trained to predict SFA in patients with CSC after laser treatment. The SFA results predicted by machine learning were compared with the actual patient prognoses. Based on the initial detailed investigation, we constructed a simplified model using fewer clinical features and OCT features for convenient application.

Results: During the internal validation, random forest performed best in SFA prediction, with accuracies of 0.651±0.068, 0.753±0.065 and 0.818±0.058 at 1, 3 and 6 months, respectively. In the external validation, XGBoost performed best at SFA prediction with accuracies of 0.734, 0.727, and 0.900 at 1, 3 and 6 months, respectively. The simplified model showed a comparable level of predictive power.

Conclusions: Machine learning can achieve high accuracy in long-term SFA predictions and identify the features relevant to CSC patients' prognoses. Our study provides an individualized reference for ophthalmologists to treat and create a follow-up schedule for CSC patients.
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http://dx.doi.org/10.21037/atm-20-1519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940879PMC
February 2021

Can environmental information disclosure promote the high-quality development of enterprises? The mediating effect of intellectual capital.

Environ Sci Pollut Res Int 2021 Jun 16;28(24):30743-30757. Epub 2021 Feb 16.

School of Economics and Management, Southeast University, Nanjing, 211100, People's Republic of China.

The Chinese government has given a high priority to economic high-quality development (HQD) in recent years. This study empirically examines whether environmental information disclosure (EID) can promote corporate HQD using a sample of 302 Chinese listed companies from 2012 to 2018. The results show that EID has a positive impact on firms' HQD and intellectual capital plays a mediating role in this relationship. The results remain robust and valid after a series of endogenous and robustness tests. This study significantly contributes to the existing EID literature by exploring the integrated effect of EID on corporate HQD through constructing a comprehensive indicator to measure corporate HQD, which includes economic performance, environmental performance, and social performance. The findings of our study also add impetus for enterprises to improve their EID.
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http://dx.doi.org/10.1007/s11356-021-12921-xDOI Listing
June 2021

Three-dimensional spiral CT observation of the facet joints of the lower cervical spine and its clinical significance.

Eur Spine J 2021 06 30;30(6):1536-1541. Epub 2021 Jan 30.

Xuzhou Medical University Affiliated Hospital, Xuzhou, China.

Objective: By observing the 3D anatomy of normal adult cervical facet joints, using the picture archiving and communication system to measure its 3D parameters and discussing its clinical significance, the aim of this study was to provide a reliable morphological basis for the design and manufacture of lower cervical facet joint interface distractors.

Methods: We selected 200 patients who underwent cervical spine 3D spiral computed tomography (CT) examination in the imaging department of our hospital from September 2019 to May 2020 and whose spiral CT images showed no cervical spinal canal stenosis, cervical disc herniation, obvious bone hyperplasia, or infection. The anterior and posterior diameters of the facet joints on both sides of the cervical spine, the space between the joints, and the left and right diameters were measured on the sagittal, cross-sectional and coronal planes after reconstruction with 3D spiral CT.

Results: The anterior and posterior diameters of the facet joints of the cervical spine, the space between the joints, and the left and right diameters all increased from top to bottom along the cervical spine. The 3D parameters of the C2-3~C6-7 segments were significantly different between the male and female groups.

Conclusion: The anteroposterior diameter, joint space interval, and left and right diameter of cervical facet joints are different in each segment and between the sexes. The lower cervical facet joint interface fusion device designed according to the measurement results can fully meet the needs of most patients.
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http://dx.doi.org/10.1007/s00586-021-06743-1DOI Listing
June 2021

Acid-Responsive Adamantane-Cored Amphiphilic Block Polymers as Platforms for Drug Delivery.

Nanomaterials (Basel) 2021 Jan 13;11(1). Epub 2021 Jan 13.

School of Chemical Engineering & Light Industry, Guangdong University of Technology, Guangzhou 510006, China.

Four-arm star-shaped (denoted as 'S') polymer adamantane-[poly(lactic--glycolic acid)--poly(-diethylaminoethyl methacrylate) poly(ethylene glycol) monomethyl ether] (S-PLGA-D-P) and its linear (denoted as 'L') counterpart (L-PLGA-D-P) were synthesized, then their self-assembled micelles were further developed to be platforms for anticancer drug delivery. Two types of polymeric micelles exhibited strong pH-responsiveness and good drug loading capacity (21.6% for S-PLGA-D-P and 22.9% for L-PLGA-D-P). Using doxorubicin (DOX) as the model drug, their DOX-loaded micelles displayed well controlled drug release behavior (18.5-19.0% of DOX release at pH 7.4 and 77.6-78.8% of DOX release at pH 5.0 within 80 h), good cytocompatibility against NIH-3T3 cells and effective anticancer efficacy against MCF-7 cells. However, the star-shaped polymeric micelles exhibited preferable stability, which was confirmed by the lower critical micelle concentration (CMC 0.0034 mg/mL) and decrease rate of particle sizes after 7 days incubation (3.5%), compared with the linear polymeric micelle L-PLGA-D-P (CMC 0.0070 mg/mL, decrease rate of particle sizes was 9.6%). Overall, these developed polymeric micelles have promising application as drug delivery system in cancer therapy.
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http://dx.doi.org/10.3390/nano11010188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828523PMC
January 2021

Cerebellum-Specific Deletion of the GABA Receptor δ Subunit Leads to Sex-Specific Disruption of Behavior.

Cell Rep 2020 11;33(5):108338

Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABA subunit-containing GABA receptors (δGABARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABA (cerebellar [cb] δ knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and in turn, leads to differential activation of cb output regions as well as many cortical and subcortical brain areas involved in cognition, anxiety-like behaviors, and the stress response. Cb δ KO mice display deficits in many behaviors, but motor function is normal. Strikingly, δGABA deletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that δGABARs enable the cerebellum to control diverse behaviors not previously associated with the cerebellum in a sex-dependent manner. These insights may contribute to a better understanding of the mechanisms that underlie behavioral abnormalities in psychiatric and neurodevelopmental disorders that display a gender bias.
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http://dx.doi.org/10.1016/j.celrep.2020.108338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700496PMC
November 2020

Deep learning from "passive feeding" to "selective eating" of real-world data.

NPJ Digit Med 2020 30;3:143. Epub 2020 Oct 30.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, 510060 Guangzhou, China.

Artificial intelligence (AI) based on deep learning has shown excellent diagnostic performance in detecting various diseases with good-quality clinical images. Recently, AI diagnostic systems developed from ultra-widefield fundus (UWF) images have become popular standard-of-care tools in screening for ocular fundus diseases. However, in real-world settings, these systems must base their diagnoses on images with uncontrolled quality ("passive feeding"), leading to uncertainty about their performance. Here, using 40,562 UWF images, we develop a deep learning-based image filtering system (DLIFS) for detecting and filtering out poor-quality images in an automated fashion such that only good-quality images are transferred to the subsequent AI diagnostic system ("selective eating"). In three independent datasets from different clinical institutions, the DLIFS performed well with sensitivities of 96.9%, 95.6% and 96.6%, and specificities of 96.6%, 97.9% and 98.8%, respectively. Furthermore, we show that the application of our DLIFS significantly improves the performance of established AI diagnostic systems in real-world settings. Our work demonstrates that "selective eating" of real-world data is necessary and needs to be considered in the development of image-based AI systems.
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http://dx.doi.org/10.1038/s41746-020-00350-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603327PMC
October 2020

DLEU2: A Meaningful Long Noncoding RNA in Oncogenesis.

Curr Pharm Des 2021 ;27(20):2337-2343

College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: Long non-coding RNA (lncRNA) with little or no coding ability has shown a variety of biological functions in cancer, including epigenetic regulation, DNA damage, regulation of microRNAs, and participation in signal transduction pathways. LncRNA can be used as an oncogene and tumor suppressor gene through transcriptional regulation in cancer. For example, the over-expressed lncRNA DLEU2 promotes the occurrence of laryngeal cancer, lung cancer, hepatocellular carcinoma, etc., and inhibits the progression of chronic lymphocytic leukemia. Deleted in Lymphocytic Leukemia 2 (DLEU2), as one of the long non-coding RNAs, was first found in chronic lymphoblastic leukemia and drawn into the progress of innumerable cancers. The molecular mechanism of DLEU2 in multiple tumors will be revealed.

Methods: In this review, current studies on the biological functions and mechanisms of DLEU2 in tumors are summarized and analyzed; related researches are systematically retrieved and collected through PubMed.

Results: DLEU2, a novel cancer-related lncRNA, has been demonstrated to be abnormally expressed in various malignant tumors, including leukemia, esophageal cancer, lung cancer, glioma, hepatocellular carcinoma, malignant pleural mesothelioma, bladder cancer, pancreatic cancer, pharynx and throat cancer, renal clear cell carcinoma, breast cancer, osteosarcoma. Besides, lncRNA DLEU2 has been shown to be involved in the process of proliferation, migration, invasion and inhibition of apoptosis of cancer cells.

Conclusion: Due to the biological functions and mechanisms involved in DLEU2, it may represent an available biomarker or potential therapeutic target in a variety of malignant tumors.
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http://dx.doi.org/10.2174/1381612826666201026150857DOI Listing
January 2021

CASC15: A Tumor-Associated Long Non-Coding RNA.

Curr Pharm Des 2021 ;27(1):127-134

College of Medical Science, China Three Gorges University, Yichang443002, China.

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors.

Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarized the specific pathophysiological mechanism of CASC15.

Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma and nasopharyngeal carcinoma. However, CASC15 has been found to be down-expressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors.

Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.
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http://dx.doi.org/10.2174/1381612826666200922153701DOI Listing
April 2021

Oncogenic LncRNA CASC9 in Cancer Progression.

Curr Pharm Des 2021 ;27(4):575-582

China Three Gorges University, School of Medicine, Yichang, 443002, China.

Background: Long non-coding RNAs (LncRNAs), with the length of over 200 nucleotides, that originate from intergenic, antisense, or promoter-proximal regions, are a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, firstly found its oncogenic function in esophageal cancer. In the following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies.

Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, and the associated studies collected in systematic retrieval of PubMed used lncRNA and CASA9 as keywords.

Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depressing cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 as closely related to the neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/ therapeutic potential of CASC9 in various human cancers.

Conclusion: Long non-coding RNA CASC9 likely serve as useful disease biomarkers or therapeutic targets which be effectively applied in the treatment of different kinds of cancers.
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http://dx.doi.org/10.2174/1381612826666200917150130DOI Listing
April 2021

Deep learning for automated glaucomatous optic neuropathy detection from ultra-widefield fundus images.

Br J Ophthalmol 2020 Sep 16. Epub 2020 Sep 16.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, China

Background/aims: To develop a deep learning system for automated glaucomatous optic neuropathy (GON) detection using ultra-widefield fundus (UWF) images.

Methods: We trained, validated and externally evaluated a deep learning system for GON detection based on 22 972 UWF images from 10 590 subjects that were collected at 4 different institutions in China and Japan. The InceptionResNetV2 neural network architecture was used to develop the system. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were used to assess the performance of detecting GON by the system. The data set from the Zhongshan Ophthalmic Center (ZOC) was selected to compare the performance of the system to that of ophthalmologists who mainly conducted UWF image analysis in clinics.

Results: The system for GON detection achieved AUCs of 0.983-0.999 with sensitivities of 97.5-98.2% and specificities of 94.3-98.4% in four independent data sets. The most common reasons for false-negative results were confounding optic disc characteristics caused by high myopia or pathological myopia (n=39 (53%)). The leading cause for false-positive results was having other fundus lesions (n=401 (96%)). The performance of the system in the ZOC data set was comparable to that of an experienced ophthalmologist (p>0.05).

Conclusion: Our deep learning system can accurately detect GON from UWF images in an automated fashion. It may be used as a screening tool to improve the accessibility of screening and promote the early diagnosis and management of glaucoma.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317327DOI Listing
September 2020

Artificial intelligence manages congenital cataract with individualized prediction and telehealth computing.

NPJ Digit Med 2020 28;3:112. Epub 2020 Aug 28.

Department of Ophthalmology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
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http://dx.doi.org/10.1038/s41746-020-00319-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455726PMC
August 2020

Climbing fiber synapses rapidly and transiently inhibit neighboring Purkinje cells via ephaptic coupling.

Nat Neurosci 2020 11 7;23(11):1399-1409. Epub 2020 Sep 7.

Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Climbing fibers from the inferior olive make strong excitatory synapses onto cerebellar Purkinje cell (PC) dendrites and trigger distinctive responses known as complex spikes. We found that, in awake mice, a complex spike in one PC suppressed conventional simple spikes in neighboring PCs for several milliseconds. This involved a new ephaptic coupling, in which an excitatory synapse generated large negative extracellular signals that nonsynaptically inhibited neighboring PCs. The distance dependence of complex spike-simple spike ephaptic signaling, combined with the known CF divergence, allowed a single inferior olive neuron to influence the output of the cerebellum by synchronously suppressing the firing of potentially over 100 PCs. Optogenetic studies in vivo and dynamic clamp studies in slice indicated that such brief PC suppression, as a result of either ephaptic signaling or other mechanisms, could effectively promote firing in neurons in the deep cerebellar nuclei with remarkable speed and precision.
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http://dx.doi.org/10.1038/s41593-020-0701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606706PMC
November 2020

Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway.

Neurochem Res 2020 Oct 13;45(10):2516-2526. Epub 2020 Aug 13.

Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, 256603, Shandong, China.

Epilepsy is one of the most common diseases of the central nervous system. Recent studies have shown that a variety of inflammatory mediators play a key role in the pathogenesis of the disease. Ibuprofen (IBP) is a well-known anti-inflammatory agent that reduces the neuroinflammatory response and neuronal damage. In this study, we examined the effect of IBP in a rat model of pentylenetetrazol (PTZ)-induced chronic epilepsy. PTZ injection was given a total of 15 times on alternate days (over a period of 29 days) to induce epilepsy. The effects of IBP were evaluated by behavioral observation, EEG recording, Nissl staining, immunohistochemistry, Western blot analysis, and electrophysiological recording. The results showed that IBP alone affected the expression of cyclooxygenase-2 (COX-2) and neuronal excitability but did not cause epilepsy. IBP reduced seizure scores in the PTZ-treated rats, and it minimized the loss of hippocampal neurons. In addition, IBP decreased the secretion of COX-2, inhibited the activation of the NOD-like receptor 3 inflammasome, and reduced the secretion of the inflammatory cytokine interleukin-18. Furthermore, the results of whole-cell patch-clamp revealed that IBP affected action potential properties, including frequency, latency and duration in epileptic rats, suggesting that it may impact neuronal excitability. These effects of IBP may underlie its antiepileptic and neuroprotective actions.
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http://dx.doi.org/10.1007/s11064-020-03109-9DOI Listing
October 2020

CDKN2B-AS1: An Indispensable Long Non-coding RNA in Multiple Diseases.

Curr Pharm Des 2020 ;26(41):5335-5346

Department of Biochemistry and Molecular Biology, College of Medical Science, China Three Gorges University, Yichang 443002, China.

Background: In view of the roles of long non-coding RNA CDKN2B antisense RNA 1 (CDKN2BAS1) in various human diseases, we investigated the function of CDKN2B-AS1 and explored its therapeutic and prognostic target value in multiple biological processes. The aim of this review was to explore the molecular mechanism and clinical significance of CDKN2B-AS1 in various types of diseases.

Materials And Methods: In this review, the biological functions and mechanisms of lncRNA CDKN2B-AS1 in a variety of pathophysiological processes were summarized and analyzed. The correlated studies were collected via a systematic search of PubMed, Wiley Online Library, and ScienceDirect.

Results: CDKN2B-AS1 is a potential long non-coding RNA that has been shown to be aberrantly expressed in various malignancies, containing hepatocellular carcinoma, intrahepatic cholangiocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colonic adenocarcinoma, cervical cancer, ovarian cancer, breast cancer, glioma, lung cancer, laryngeal squamous cell carcinoma and osteosarcoma, involving in the processes of tumor cells proliferation, migration, invasion and inhibition of tumor cells apoptosis. Besides, CDKN2B-AS1 has been proved implicated in numerous non-malignant diseases, such as idiopathic pulmonary fibrosis, endometriosis, inflammatory bowel disease, intracranial aneurysm, diabetes mellitus and its complications, primary open angle glaucoma, ischemic stroke, atherosclerosis, coronary artery diseases, hypertension and heart failure, participating in the procession of lipid, carbohydrate metabolism and inflammation regulation.

Conclusion: Long non-coding RNA CDKN2B-AS1 likely serves as a promising therapeutic target or prognosis biomarker in multiple human diseases.
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http://dx.doi.org/10.2174/1381612826666200806102424DOI Listing
April 2021

Application of artificial intelligence in anterior segment ophthalmic diseases: diversity and standardization.

Ann Transl Med 2020 Jun;8(11):714

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Artificial intelligence (AI) based on machine learning (ML) and deep learning (DL) techniques has gained tremendous global interest in this era. Recent studies have demonstrated the potential of AI systems to provide improved capability in various tasks, especially in image recognition field. As an image-centric subspecialty, ophthalmology has become one of the frontiers of AI research. Trained on optical coherence tomography, slit-lamp images and even ordinary eye images, AI can achieve robust performance in the detection of glaucoma, corneal arcus and cataracts. Moreover, AI models based on other forms of data also performed satisfactorily. Nevertheless, several challenges with AI application in ophthalmology have also arisen, including standardization of data sets, validation and applicability of AI models, and ethical issues. In this review, we provided a summary of the state-of-the-art AI application in anterior segment ophthalmic diseases, potential challenges in clinical implementation and our prospects.
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http://dx.doi.org/10.21037/atm-20-976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327317PMC
June 2020
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