The Prediction Models for High-Risk Population of Stroke Based on Logistic Regressive Analysis and Lightgbm Algorithm Separately.

Background: We aimed to investigate the high-risk factors of stroke through logistic regressive analysis and using LightGBM algorithm separately. The results of the two models were compared for instructing the prevention of stroke. Methods: Samples of residents older than 40 years of age were collected from two medical examination centers in Jiaxing, China from 2018 to 2019. Among the total 2124 subjects, 1059 subjects were middle-aged people (40-59 years old) and 1065 subjects were elder-aged people (≥60 years old). Their demographic characteristics, medical history, family history, eating habits etc. were recorded and separately input into logistic regressive analysis and LightGBM algorithm to build the prediction models of high-risk population of stroke. Four values including F1 score, accuracy, recall rate and AUROC were compared between the two models. Results: The risk factors of stroke were positively correlated with age, while negatively correlated with the frequency of fruit consumption and taste preference. People with low-salt diet were associated with less risk of stroke than those with high-salt diet, and male had higher stroke risk than female. Meanwhile, the risk factors were positively correlated with the frequency of alcohol consumption in the middle-aged group, and negatively correlated with the education level in the elder-aged group. Furthermore, the four values from LightGBM were higher than those from logistic regression, except for the recall value of the middle-aged group. Conclusion: Age, gender, family history of hypertension and diabetes, the frequency of fruit consumption, alcohol and dairy products, taste preference, and education level could as the risk predictive factors of stroke. The Model of using LightGBM algorithm is more accurate than that using logistic regressive analysis.

Leucine rich alpha-2-glycoprotein 1 (Lrg1) silencing protects against sepsis-mediated brain injury by inhibiting transforming growth factor beta1 (TGFß1)/SMAD signaling pathway.

Sepsis-associated encephalopathy (SAE) is key manifestation of sepsis which is responsible for increased morbidity and mortality. Leucine rich alpha-2-glycoprotein 1 (Lrg1) is a secreted protein implicated in a variety of diseases. We aimed to explore the effects and potential mechanism of Lrg1 on sepsis-mediated brain injury. A sepsis-induced brain damage mice model was established. Then, ELISA was utilized to detect the levels of inflammatory factors in brain tissues. Behavioral performance, spatial learning and memory of mice were evaluated by open field test and Morris water maze test. The number of neurons was tested by H&E staining. Lrg1 expression was evaluated by RT-qPCR and western blot. In vitro, mouse hippocampal neuronal cell line (HT22) was stimulated by lipopolysaccharide (LPS). After Lrg1 silencing, cell viability was determined using CCK-8 and cell apoptosis was assessed by TUNEL. The levels of inflammatory factors were detected by ELISA. Moreover, western blot was applied to analyze the expression of proteins in transforming growth factor beta1 (TGFß1)/SMAD signaling. Results revealed that mice in the model group showed obvious behavioral changes. Lrg1 was highly expressed in the brain tissues of model mice. Besides, Lrg1 knockdown suppressed the inflammation and apoptosis of LPS-induced HT22 cells. Moreover, Lrg1 silencing caused the inactivation of TGFß1/SMAD signaling. Rescue assays confirmed that TGFß1 overexpression reversed the impacts of Lrg1 deletion on the inflammation and apoptosis in LPS-induced HT22 cells. Collectively, Lrg1 silencing alleviates brain injury in SAE via inhibiting TGFß1/SMAD signaling, implying that Lrg1 might serve as a promising target for SAE treatment.

Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy.

BACKGROUND: Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM: To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS: ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS: Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC50) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo. CONCLUSION: We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.

Investigation of action pattern of a novel chondroitin sulfate/dermatan sulfate 4-O-endosulfatase.

Recently, a novel CS/DS 4-O-endosulfatase was identified from a marine bacterium and its catalytic mechanism was investigated further (Wang, W., et. al (2015) J. Biol. Chem.290, 7823-7832; Wang, S., et. al (2019) Front. Microbiol.10, 1309). In the study herein, we provide new insight about the structural characteristics of the substrate which determine the activity of this enzyme. The substrate specificities of the 4-O-endosulfatase were probed by using libraries of structure-defined CS/DS oligosaccharides issued from synthetic and enzymatic sources. We found that this 4-O-endosulfatase effectively remove the 4-O-sulfate of disaccharide sequences GlcUAß1-3GalNAc(4S) or GlcUAß1-3GalNAc(4S,6S) in all tested hexasaccharides. The sulfated GalNac residue is resistant to the enzyme when adjacent uronic residues are sulfated as shown by the lack of enzymatic desulfation of GlcUAß1-3GalNAc(4S) connected to a disaccharide GlcUA(2S)ß1-3GalNAc(6S) in an octasaccharide. The 3-O-sulfation of GlcUA was also shown to hinder the action of this enzyme. The 4-O-endosulfatase exhibited an oriented action from the reducing to the non-reducing whatever the saturation or not of the non-reducing end. Finally, the activity of the 4-O-endosulfatase decreases with the increase in substrate size. With the deeper understanding of this novel 4-O-endosulfatase, such chondroitin sulfate (CS)/dermatan sulfate (DS) sulfatase is a useful tool for exploring the structure-function relationship of CS/DS.

[Gene characteristics and changing trend of neonatal thalassemia in Dongguan, China].

OBJECTIVE: To study the gene distribution characteristics of neonatal thalassemia in Dongguan, China and the changing trend of the gene distribution characteristics of neonates with thalassemia in Dongguan in 2014-2018. METHODS: A retrospective analysis was performed for the data on neonatal thalassemia screening from the Dongguan Neonatal Disease Screening System between January 2014 and December 2018. A total of 616 718 neonates were enrolled who were born in Dongguan. RESULTS: Among the 616 718 neonates, 52 308 were positive for primary screening, 10 366 were recalled, 8 576 underwent genetic diagnosis, and 6 432 were confirmed with thalassemia by genetic diagnosis. The carrying rates of thalassemia genes in 2014-2018 were 5.81%, 5.47%, 5.96%, 6.91%, and 7.90% respectively, and showed an upward trend (P<0.001). The positive rates of neonatal thalassemia screening in 2014-2018 were 9.12%, 8.34%, 7.54%, 8.13%, and 9.32% respectively (P<0.001). The positive rates of genetic diagnosis of neonatal thalassemia in 2014-2018 were 0.89%, 1.11%, 1.24%, 0.90%, and 1.09% respectively (P<0.001). In 2014-2018, 5 098 cases of α-thalassemia were detected, accounting for 79.26% of all cases, and 1 230 cases of ß-thalassemia were detected, accounting for 19.12% of all cases. The detection rate of α-thalassemia was significantly higher than that of ß-thalassemia in each year (P<0.001). In 2014-2018, static α-thalassemia, mild α-thalassemia, and mild ß-thalassemia were the main types observed in neonates. CONCLUSIONS: Most of the neonates with thalassemia have α-thalassemia in Dongguan, with static α-thalassemia and mild α-thalassemia as the main types. The carrying rate of thalassemia genes keeps increasing in neonates in Dongguan, and the prevention and treatment of thalassemia is still challenging.

Quantitative Analysis of Retinal Microvascular Changes after Conbercept Therapy in Branch Retinal Vein Occlusion Using Optical Coherence Tomography Angiography.

PURPOSE: To quantitatively evaluate microvascular changes in eyes with macular oedema due to branch retinal vein occlusion (BRVO) using optical coherence tomography angiography (OCTA) before and after intravitreal conbercept injection and the correlation of such changes with best-corrected visual acuity (BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients treated with a single intravitreal injection of conbercept for macular oedema due to BRVO were included in this study. The automatically measured values of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter, the vessel density within a 300 µm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area and the retinal thickness were obtained via OCTA before and at 1 month after initial injection and compared with those of age- and sex- matched healthy subjects. RESULTS: In BRVO eyes, the vascular density in the SCP and DCP, the FD-300 and the flow area of choriocapillaris were significantly lower than those in healthy eyes, while the AI and the retinal thickness were significantly increased. After treatment, the retinal thickness in eyes with BRVO was significantly decreased in all quadrants, and the mean BCVA dramatically increased from 20/162 to 20/78 (p = 0.0017). The mean flow area of choriocapillaris significantly improved after treatment. Moreover, negative correlations between the logMAR BCVA and the whole vascular density in the SCP and DCP as well as the flow area of choriocapillaris were observed. CONCLUSION: OCTA enables non-invasive, layer-specific and quantitative assessment of microvascular changes in eyes with BRVO before and after treatment, and it can be used as a valuable imaging tool for the evaluation of the follow-up in BRVO patients.

Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography.

AIM: To investigate microvascular changes in eyes with central retinal vein occlusion (CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity (BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography (OCTA) automatic measurements of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter (PERIM), the vessel density within a 300-µm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age- and sex-matched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were all significantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher (all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65 (P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness. CONCLUSION: OCTA enables the non-invasive, layer-specific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

Macular microvasculature features before and after vitrectomy in idiopathic macular epiretinal membrane: an OCT angiography analysis.

PURPOSE: To evaluate pre-operative and post-operative morphologic characteristics in idiopathic macular epiretinal membrane (ERM) by optical coherence tomography angiography (OCTA). METHODS: Thirty-three subjects with unilateral idiopathic ERM were enrolled and the contralateral eyes served as controls. Vascular parameters including superficial capillary plexus (SCP), deep capillary plexus (DCP), outer capillary plexus (OCP), and choroidal capillary plexus (CCP) were evaluated by OCTA. RESULTS: The superficial foveal avascular zone (FAZ) was significantly smaller in eyes with ERM (P < 0.0001). The vessel densities (VDs) were significantly increased in the fovea but dramatically decreased in the parafovea in SCP and DCP of ERM eyes (all P < 0.0001), in contrast to those in OCP and CCP. The blood flow was augmented in OCP but declined in choroid compared with the controls. In CCP, the mean foveal VD in ERM was significantly smaller (P = 0.023), whereas parafoveal VD did not significantly change (P = 0.66). At 6 months after surgery, flow area was decreased in OCP (P = 0.0007), and foveal and parafoveal VDs were significantly altered in all layers except the foveal VD in OCP and the choroid (all P < 0.05). The total and inner retinal thickness of the fovea and parafovea were correlated with pre-operative and post-operative visual outcomes, respectively. Smaller FAZ and greater interocular differences between post-operative and fellow eyes in FAZ were associated with worse post-operative visual outcomes. CONCLUSIONS: OCTA provides a better display of the vascular network of the retina and choroid to evaluate the severity and surgical prognosis of ERM patients.

A tensor-mass method-based vascular model and its performance evaluation for interventional surgery virtual reality simulator.

BACKGROUND: Physics-based vascular modelling is an essential issue to be addressed in the development of the endovascular interventional surgery training system, which helps to shorten the training period of novice surgeons to obtain dexterous skills of surgical operation. METHODS: A blood vessel model based on tensor-mass method (TMM) is formulated and implemented in this context. A multimodel representation is adopted for the vascular model, including the mechanical, visual, and collision model. Triangular and tetrahedral TMM are formulated and implemented in Simulation Open-source Framework Architecture (SOFA). An extensional formulation and analysis of two typical methods are implemented in SOFA. Meanwhile, a set of experiments were conducted to test the refresh rate, the stability, and the visual realism of the vascular deformation simulation, integrating with TMM, mass-spring model, and finite element method. RESULTS: The experimental and subjects' testing results prove that TMM outperforms the current physically based methods in realistic and real-time vascular deformation simulation, which provides a refresh rate up to 256 frame per second on a triangular vascular topology. CONCLUSIONS: The vascular model presented herein provides a fundamental module meeting the real-time and realistic requirements of our endovascular interventional surgery simulator.

Sequencing of chondroitin sulfate oligosaccharides using a novel exolyase from a marine bacterium that degrades hyaluronan and chondroitin sulfate/dermatan sulfate.

Glycosaminoglycans (GAGs) are a family of chemically heterogeneous polysaccharides that play important roles in physiological and pathological processes. Owing to the structural complexity of GAGs, their sophisticated chemical structures and biological functions have not been extensively studied. Lyases that cleave GAGs are important tools for structural analysis. Although various GAG lyases have been identified, exolytic lyases with unique enzymatic property are urgently needed for GAG sequencing. In the present study, a putative exolytic GAG lyase from a marine bacterium was recombinantly expressed and characterized in detail. Since it showed exolytic lyase activity toward hyaluronan (HA), chondroitin sulfate (CS), and dermatan sulfate (DS), it was designated as HCDLase. This novel exolyase exhibited the highest activity in Tris-HCl buffer (pH 7.0) at 30°C. Especially, it showed a specific activity that released 2-aminobenzamide (2-AB)-labeled disaccharides from the reducing end of 2-AB-labeled CS oligosaccharides, which suggest that HCDLase is not only a novel exolytic lyase that can split disaccharide residues from the reducing termini of sugar chains but also a useful tool for the sequencing of CS chains. Notably, HCDLase could not digest 2-AB-labeled oligosaccharides from HA, DS, or unsulfated chondroitin, which indicated that sulfates and bond types affect the catalytic activity of HCDLase. Finally, this enzyme combined with CSase ABC was successfully applied for the sequencing of several CS hexa- and octasaccharides with complex structures. The identification of HCDLase provides a useful tool for CS-related research and applications.