Machine Learning Analysis Classifies Patients with Primary Angle-Closure Glaucoma Using Abnormal Brain White Matter Function.

Objective: Primary angle-closure glaucoma (PACG) is a globally prevalent, irreversible eye disease leading to blindness. Previous neuroimaging studies demonstrated that PACG patients were associated with gray matter function changes. However, whether the white matter(WM) function changes in PACG patients remains unknown. The purpose of the study is to investigate WM function changes in the PACG patients. Methods: In total, 40 PACG patients and 40 well-matched HCs participated in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared between-group differences between PACG patients and HC in the WM function using amplitude of low-frequency fluctuations (ALFF). In addition, the SVM method was applied to the construction of the PACG classification model. Results: Compared with the HC group, ALFF was attenuated in right posterior thalamic radiation (include optic radiation), splenium of corpus callosum, and left tapetum in the PACG group, the results are statistically significant (GRF correction, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, the SVM classification had an accuracy of 80.0% and an area under the curve (AUC) of 0.86 for distinguishing patients with PACG from HC. Conclusion: The findings of our study uncover abnormal WM functional alterations in PACG patients and mainly involves vision-related regions. These findings provide new insights into widespread brain damage in PACG from an alternative WM functional perspective.

Development and validation of a nomogram to predict overall survival of conjunctival melanoma: a population-based study.

Background: Conjunctival melanoma (CM) is a rare, invasive tumor in the eye that readily metastasizes and spreads. Based on some significant clinicopathological information, we aimed to develop a prognostic model to predict the overall survival (OS) of CM patients. Methods: Data of patients diagnosed with CM from 2000 to 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were extracted and integrated based on competing risk regression to build a nomogram. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration plots were used to evaluate the performance of the nomogram. Results: The study included 272 patients with CM, with a median age of 63 years. A nomogram was developed using age and tumor-node-metastasis (TNM) stage as variables. The model's C-index was 0.755, and the area under the curve (AUC) was 0.774, 0.812, and 0.815 at 5, 8, and 10 years, respectively. The calibration plot used to predict CM demonstrated good consistency between the predicted OS probability and the actual OS probability. Conclusions: We have developed a nomogram model to predict the OS of patients with CM, which can predict the survival of these patients. The model's prognostic value is higher than that of the American Joint Committee on Cancer (AJCC) staging system alone. This tool can help evaluate the tumor-specific prognosis, identify patients at high risk of cancer-specific death, and guide clinical decision-making.

Altered functional connectivity between the default mode network in primary angle-closure glaucoma patients.

Previous studies have recognized glaucoma as a neurodegenerative disease that causes extensive brain damage and is closely associated with cognitive function. In this study, we employed functional MRI to examine the intrinsic functional connectivity patterns of the default mode network (DMN) in patients diagnosed with primary angle-closure glaucoma (PACG), exploring its association with cognitive dysfunction. A total of 34 patients diagnosed with PACG and 34 healthy controls (HC), who were matched in terms of sex, age, and education, were included in the control group. The posterior cingulate cortex (PCC) was selected as the region of interest to examine functional connectivity alterations. Compared with the HC group, functional connectivity was attenuated in left anterior cingulum cortex and left paracentral lobule between with PCC in the PACG group, the results are statistically significant. Our study revealed that patients with PACG exhibit weakened functional connectivity within the DMN. This finding suggests the presence of a neurological mechanism that is associated with both visual dysfunction and cognitive impairments in PACG patients. Furthermore, our study provides neuroimaging evidence that can aid in the exploration of spontaneous neurological alterations and facilitate a deeper investigation of alterations in the visual conduction pathways of PACG patients.

Comparisons of artificial intelligence algorithms in automatic segmentation for fungal keratitis diagnosis by anterior segment images.

Purpose: This study combines automatic segmentation and manual fine-tuning with an early fusion method to provide efficient clinical auxiliary diagnostic efficiency for fungal keratitis. Methods: First, 423 high-quality anterior segment images of keratitis were collected in the Department of Ophthalmology of the Jiangxi Provincial People's Hospital (China). The images were divided into fungal keratitis and non-fungal keratitis by a senior ophthalmologist, and all images were divided randomly into training and testing sets at a ratio of 8:2. Then, two deep learning models were constructed for diagnosing fungal keratitis. Model 1 included a deep learning model composed of the DenseNet 121, mobienet_v2, and squeezentet1_0 models, the least absolute shrinkage and selection operator (LASSO) model, and the multi-layer perception (MLP) classifier. Model 2 included an automatic segmentation program and the deep learning model already described. Finally, the performance of Model 1 and Model 2 was compared. Results: In the testing set, the accuracy, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic (ROC) curve (AUC) of Model 1 reached 77.65, 86.05, 76.19, 81.42%, and 0.839, respectively. For Model 2, accuracy improved by 6.87%, sensitivity by 4.43%, specificity by 9.52%, F1-score by 7.38%, and AUC by 0.086, respectively. Conclusion: The models in our study could provide efficient clinical auxiliary diagnostic efficiency for fungal keratitis.

Altered dynamic functional connectivity in the primary visual cortex in patients with primary angle-closure glaucoma.

Purpose: Glaucoma is the main blindness-causing disease in the world. Previous neuroimaging studies demonstrated that glaucoma not only causes the loss of optic ganglion cells but also leads to the abnormal function of the optic nerve pathway and the visual cortex. However, previous studies also reported that patients with glaucoma have dysfunction in the visual cortex in a static state. Whether or not patients with primary angle-closure glaucoma (PACG) were accompanied by dynamic functional connectivity (FC) changes in the primary visual cortex (V1) remains unknown. Methods: A total of 34 patients with PACG (23 men and 11 women) and 34 well-matched healthy controls (HCs) were enrolled in the study. The dynamic functional connectivity (dFC) with the sliding window method was applied to investigate the dynamic functional connectivity changes in the V1. Results: Compared with HCs, patients with PACG showed increased dFC values between left V1 and bilateral calcarine (CAL). Meanwhile, patients with PACG showed increased dFC values between right V1 and bilateral CAL. Conclusion: Our study demonstrated that patients with PACG showed increased dFC within the visual network, which might indicate the increased variability FC in the V1 in patients with PACG.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

PURPOSE: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. RESULTS: After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. CONCLUSION: Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Evaluation and Validation of the Limited Sampling Strategy of Polymyxin B in Patients with Multidrug-Resistant Gram-Negative Infection.

Polymyxin B (PMB) is the final option for treating multidrug-resistant Gram-negative bacterial infections. The acceptable pharmacokinetic/pharmacodynamic target is an area under the concentration-time curve across 24 h at a steady state (AUCss,24h) of 50-100 mg·h/L. The limited sampling strategy (LSS) is useful for predicting AUC values. However, establishing an LSS is a time-consuming process requiring a relatively dense sampling of patients. Further, given the variability among different centers, the predictability of LSSs is frequently questioned when it is extrapolated to other clinical centers. Currently, limited data are available on a reliable PMB LSS for estimating AUCss,24h. This study assessed and validated the practicability of LSSs established in the literature based on data from our center to provide reliable and ready-made PMB LSSs for laboratories performing therapeutic drug monitoring (TDM) of PMB. The influence of infusion and sampling time errors on predictability was also explored to obtain the optimal time points for routine PMB TDM. Using multiple regression analysis, PMB LSSs were generated from a model group of 20 patients. A validation group (10 patients) was used to validate the established LSSs. PMB LSSs from two published studies were validated using a dataset of 30 patients from our center. A population pharmacokinetic model was established to simulate the individual plasma concentration profiles for each infusion and sampling time error regimen. Pharmacokinetic data obtained from the 30 patients were fitted to a two-compartment model. Infusion and sampling time errors observed in real-world clinical practice could considerably affect the predictability of PMB LSSs. Moreover, we identified specific LSSs to be superior in predicting PMB AUCss,24h based on different infusion times. We also discovered that sampling time error should be controlled within -10 to 15 min to obtain better predictability. The present study provides validated PMB LSSs that can more accurately predict PMB AUCss,24h in routine clinical practice, facilitating PMB TDM in other laboratories and pharmacokinetics/pharmacodynamics-based clinical studies in the future.

The Effect Of Food On The Pharmacokinetic Properties And Bioequivalence Of Two Formulations Of Levocetirizine Dihydrochloride In Healthy Chinese Volunteers.

PURPOSE: The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated. PATIENTS AND METHODS: Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software. RESULTS: Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75-107.24% and 99.98-114.69% for the maximum observed concentration, and 97.13-102.50% and 98.36-103.98% for the area under the concentration-time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported. CONCLUSION: The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers.

Deep Convolutional Neural Networks for Classifying Body Constitution Based on Face Image.

Body constitution classification is the basis and core content of traditional Chinese medicine constitution research. It is to extract the relevant laws from the complex constitution phenomenon and finally build the constitution classification system. Traditional identification methods have the disadvantages of inefficiency and low accuracy, for instance, questionnaires. This paper proposed a body constitution recognition algorithm based on deep convolutional neural network, which can classify individual constitution types according to face images. The proposed model first uses the convolutional neural network to extract the features of face image and then combines the extracted features with the color features. Finally, the fusion features are input to the Softmax classifier to get the classification result. Different comparison experiments show that the algorithm proposed in this paper can achieve the accuracy of 65.29% about the constitution classification. And its performance was accepted by Chinese medicine practitioners.

Comparative proteomic analysis of plasma proteins in patients with age-related macular degeneration.

AIM: To find the significant altered proteins in age-related macular degeneration (AMD) patients as potential biomarkers of AMD. METHODS: A comparative analysis of the protein pattern of AMD patients versus healthy controls was performed by means of proteomic analysis using two-dimensional gel electrophoresis followed by protein identification with MALDI TOF/TOF mass spectrometry. RESULTS: We identified 28 proteins that were significantly altered with clinical relevance in AMD patients. These proteins were involved in a wide range of biological functions including immune responses, growth cytokines, cell fate determination, wound healing, metabolism, and anti-oxidance. CONCLUSION: These results demonstrate the capacity of proteomic analysis of AMD patient plasma. In addition to the utility of this approach for biomarker discovery, identification of alterations in endogenous proteins in the plasma of AMD patient could improve our understanding of the disease pathogenesis.

[Treatment of otorhinolaryngologic diseases of deficient heat type with Professor XIE Qiang's Tihu Guanding needling method].

Professor XIE Qiang's Tihu Guanding needling method, a kind of acupuncture method which takes acupoints of the Conception Vessel as the primary and acupoints of the Governor Vessel as the secondary. Acupoints Lianquan (CV 23), Tiantu (CV 22), Qihai (CV 6), Zhongwan (CV 12), Baihui (GV 20) and Dazhui (GV 14) are adopted as the basic ones. Other points can be added according to various symptoms, for instance, Yingxiang (LI 20) and Yintang (GV 29) for rhinopathy, Tinggong (SI 19) and Yifeng (TE 17) for otopathy, Yan'an (Professor XIE's experience) and Shanglianquan (EX-HN 21) for pharyngopathy and Kaiyin 1 (Professor XIE's experience) and Kaiyin 2 (Professor XIE's experience) for laryngopathy. During the needle retention, rotation manipulation should be done every 5 min at Lianquan (CV 23). And the patient should be told to put the tip of one's tongue at the the palate as well as to do deep breathing to communicate the Conception Vessel and the Governor Vessel. Moxibustion is adopted at Yongquan (KI 1) to induce the up floating fire to mingmen (where the primary yang is stored). The therapeutic effect on treatment of persistent otorhinolaryngologic diseases with the above mentioned method is approve to be good.

Efficacy of Ethanol Extract of Fructus lycii and Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress: In Vivo and In Vitro Models of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects of Fructus lycii ethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments in Fructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2) in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However, Fructus lycii ethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated by Fructus lycii ethanol extract. Investigations in vitro showed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested that Fructus lycii ethanol extract and its active components lutein/zeaxanthin had protective effects on AMD in vivo and in vitro, providing novel insights into the beneficial role of Fructus lycii for AMD therapy.

[Prevention and treatment of age-related macular degeneration by extract of Fructus lycii and its constituents lutein/zeaxanthin: an in vive and in vitro experimental research].

OBJECTIVE: To investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells. METHODS: Fifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01). CONCLUSIONS: Extract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.

[Study on needling Ying method for treatment of sore throat].

To explore the mechanism of needling Ying method for treatment of sore throat. By the analysis of pathogenesis of sore throat, the authors think the key of its pathogenesis is stagnation of pathogenic factors such as hotness and phlegm accumulating, and meridian-vessel obstruction in the throat is its meridian foundation. There are several meridians passing through the throat, so the throat is closely related to viscera and meridians, and stagnation of pathogenic factors such as hotness and phlegm accumulating in the throat lead to sore throat when exogenous pathogenic factors invading or dysfunction of viscera and meridians. The treatment of needling Ying at local throat or combined with corresponding meridian point selection can dredge collaterals, dispel pathogenic factors, remove pathogenic factors to dispel swelling, resolve phlegm and dissipate stagnation and harmonize yin and yang, so as to relieve sore throat. In conclusion, needling Ying method is an important method in the treatment of sore throat.