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Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.
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Objective To investigate the effects of different concentrations of PPF on oxidative stress and apoptosis of PD model cells induced by MPP+.Methods The human neuroblastoma cell SH-SY5Y was induced by 1 mM MPP+ to establish PD cell model.In PPF treatment group,SH-SY5Y cells were stimulated with 10,20,40 and 80 μM PPF for 4 h before MPP+ induction.Cell counting kit-8(CCK-8)was performed to evaluate cell proliferation activity.H2DCF-DA fluorescent probe was used to detect ROS in cells.The levels of MDA and NADPH oxidase were analyzed by the kit.Western blot examined the protein expression of cytochrome c in mitochondria and cytoplasm,as well as the relative expression of Bcl-2,Bax and cleaved caspase-3 in SH-SY5Y cells.Apoptosis rate was analyzed by flow cytometry.Results MPP+ significantly inhibited the proliferation of SH-SY5Y cells(P<0.001),promoted the level of ROS(P<0.001),MDA(P<0.001),NADPH oxidase(P<0.01),cytochrome c in cytoplasm(P<0.01)and induced apoptosis(P<0.001)and the relative expression of pro-apoptosis protein Bax and cleaved caspase-3(P<0.01),reduced cytochrome c protein in mitochondria(P<0.01)and the relative expression of anti-apoptosis protein(P<0.01).PPF pretreatment alleviated the proliferation inhibition,oxidative stress and apoptosis promotion of SH-SY5Y cells induced by MPP+(P<0.001),and the effects of 40 μM and 80 μM on cells were more significant.Conclusion PPF pretreatment can alleviate the oxidative stress of SH-SY5Y cells induced by MMP+ and reduce apoptosis rate.
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Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P<0.001),while MAP was not significantly correlated with gestational week(P>0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.
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Objective To explore the genetic characteristics of fetuses with congenital heart diseases(CHD)diagnosed by prenatal ultrasound.Methods Data of 613 singletons with prenatal ultrasonic diagnosed CHD were retrospectively analyzed.The cardiac structural abnormalities were classified into 8 types.Whole-exome sequencing(WES)was performed for 40 fetuses since chromosomal karyotyping analysis and/or chromosomal microarray analysis(CMA)showed benign copy number variations(CNV)or variants of uncertain significance(VUS).Results Among 613 fetuses,479 fetuses underwent both chromosomal karyotyping analysis and CMA,genomic abnormalities were detected in 60 fetuses(60/479,12.53%).Among 134 fetuses underwent only CMA,genomic abnormalities were found in 4 fetuses(4/134,2.99%).According to results of chromosomal karyotyping analysis and/or CMA,abnormalities were noticed in 40 fetuses(40/568,7.04%)among 568 fetuses with isolated CHD,while in 15 fetuses(15/45,33.33%)among 45 fetuses with non-isolated CHD,respectively.Abnormality detection rate of chromosomal karyotyping analysis and/or CMA in fetuses with complex CHD(10/41,24.39%)was higher than that in fetuses with non-complex CHD(54/572,9.44%).Among complex CHD fetuses,abnormality detection rate was the highest in fetuses with conotruncal defect(CTD)combined with malformation of venous system(4/13,30.77%),while among fetuses with non-complex CHD,situs inversus viscerum had the highest detection rate(1/4,25.00%).Among 40 fetuses chromosomal karyotyping analysis and/or CMA showed benign CNV or VUS,WES indicated pathogenic CNV/likely pathogenic CNV(P/LP)in 3 fetuses,VUS in 3 fetuses and benign CNV in 34 fetuses.Conclusion Fetuses with CHD,especially extracardiac malformations had possibilities of genomic abnormalities.Fetuses with CTD combined with malformation of venous system had higher possibilities of genomic abnormalities.Compared with CMA alone,chromosomal karyotyping analysis combined with CMA was helpful for detecting genomic abnormalities.
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Background@#and Purpose Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. @*Methods@#Medical records of MG patients from 1976 to 2023 were reviewed retrospectively.Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. @*Results@#This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21–30 years) whereas male patients peaked at a higher age (61–70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17–18.64, p=0.029) analyses. @*Conclusions@#Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.
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In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse testis. We have demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilization of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O2. Through the generation of a germline-specific Epas1 knockout mouse line, and through modulation of EPAS1 levels in primary cultures of spermatogonia with the small drug molecule Daprodustat, we have demonstrated that EPAS1 is required for robust SSC function in regenerative conditions (post-transplantation and post-chemotherapy), via the regulation of key cellular processes such as metabolism. These findings shed light on the relationship between hypoxia and male fertility and will potentially facilitate optimization of in vitro culture conditions for infertility treatment pipelines using SSCs, such as those directed at pediatric cancer survivors.
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Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.
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Microbiota , Respiratory Tract Infections , Animals , Female , Mice , Pregnancy , Dendritic Cells , Diet , PropionatesABSTRACT
STATEMENT OF PROBLEM: Symptomatic denture stomatitis (DS) is a painful oral mucosal disorder that can impair quality of life in denture wearers. A complete cure of DS is difficult to achieve, and the most efficacious regimen to treat DS has not yet been conclusively established. PURPOSE: The purpose of this network meta-analysis was to assess the comparative efficacy of interventions used for the treatment of DS. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until February 2022 (PROSPERO Reg no: CRD42021271366). Network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of any form of intervention for the treatment of DS in denture wearers. Agents were ranked according to their effectiveness in the treatment of DS based on outcomes using surface under the cumulative ranking (SUCRA). RESULTS: A total of 25 articles were included in the quantitative analysis. Topical antifungal agents (risk ratio [RR]=4.37[95% confidence interval [CI]: 2.15,8.90), topical antimicrobial agents used along with systemic antifungal agents (RR=4.25[95% CI: 1.79,10.33]), systemic antifungal agents (RR=4.25[95% CI: 1.79,10.10]), photodynamic therapy (RR=4.25[95% CI: 1.75,8.98]), and topical plant products (RR=3.40[95% CI: 1.59,7.26]) were found to effectively improve DS. Microwave disinfection concurrently administered with topical antifungal agents (RR=7.38(95% CI: 2.75,19.81), microwave disinfection 7.38[95% CI: 2.75,19.81]), topical antifungal agents (RR=4.88[95% CI: 1.92,12.42]), topical plant products (RR=4.49[95% CI: 1.70,11.82]), systemic antifungal agents together with topical antimicrobial agents (RR=3.85[95% CI: 1.33,11.10]), topical antimicrobial agents (RR=3.39[95% CI: 1.17,9.81]), systemic antifungal agents (RR=3.37[95% CI: 1.21,9.34]), and photodynamic therapy or photochemotherapy (PDT) (RR=2.93[95% CI: 1.01,8.47]) were found to effectively resolve mycological DS. Topical antifungals ranked highest in the SUCRA ranking for clinical improvement, whereas microwave disinfection concurrently administered with topical antifungal agents ranked highest for mycological resolution. None of the agents demonstrated significant side effects except for topical antimicrobial agents which demonstrated altered taste and staining of oral structures. CONCLUSIONS: Available evidence suggests that topical antifungals, microwave, and systemic antifungals are effective in the treatment of DS, but confidence in these findings is low because of the limited number of studies and a high risk of bias. Additional clinical trials are needed on photodynamic therapy, topical plant products, and topical antimicrobials.
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Previous studies reported the latex from the fruit of Ficus carica L. (fig) has anti-tumor and antioxidant activities in animal models. However, its active constituents, mechanism of action, and safety remain unknown. The alcohol-precipitated fraction of fig fruit latex (AFFL) was purified and prepared for testing against non-small cell lung cancer (NSCLC). UPLC-TOF-MS/MS was used to examined the components of AFFL. We validated efficacy by researching antitumor phenotypes in vitro and constructing subcutaneous grafts of nude mice with NSCLC, as well as showing the underlying mechanism at the protein level. The results showed that 11 components of AFFL were screened. AFFL significantly inhibited the proliferation, migration, invasion, and clonogenesis of NSCLC cells, promoted cell apoptosis, inhibited tumor growth in A549 xenograft mice, but induced no obvious damage to normal mouse tissues (liver or kidney). Molecular mechanism studies revealed that AFFL could increase Caspase-1 expression in cancer cells by activating the cleavage of Caspase-3 and Caspase-9, inhibiting the activity of Bcl-2, and promoting tumor cell apoptosis. These processes cause gasdermin proteins (GSDMD and GSDME) to be cleaved, releasing N-terminal domain proteins to accumulate and perforate the cell membrane, and promoting tumor cell pyroptosis. In conclusion, our findings suggested that AFFL may promote tumor cell apoptosis and pyroptosis via the Caspase/Gasdermin/AKT signaling pathway and inhibit NSCLC growth in vitro and in vivo, demonstrating that fig latex can be developed as a functional food and drug with anti-NSCLC properties.
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Carcinoma, Non-Small-Cell Lung , Ficus , Lung Neoplasms , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/genetics , Caspases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Latex/metabolism , Gasdermins , Lung Neoplasms/metabolism , Mice, Nude , Tandem Mass Spectrometry , Signal Transduction/physiology , Apoptosis/physiology , Cell Proliferation , Cell Line, TumorABSTRACT
Objective To observe the influence of the staining phenomenon after fluorescein sodium staining on eye irritation in normal rabbits.MethodsIn the experimental rabbit eye irritation test conducted with sodium chloride eye drops, Siwei Zhenceng Bingpeng eye drops, sodium hyaluronate eye drops, sodium cromoglycate eye drops, and compound aspartate eye drops (4 in each group, half male and half female), the left eyes of rabbits were administered normal saline (self-negative control) and the right eyes were administered the experimental medicine; the eyes were stained with 1% sodium fluorescein, and eye irritation was observed and scored using slit lamp microscope for 31 days. Morphological changes of corneal epithelial staining were recorded and the incidence of staining was calculated. After the observation, the eyeballs and Hasselblad glands were examined histopathologically, and the staining rate of the left eye was compared with that of the right eye which was administered the corresponding medicine.ResultsNeither eye had any irritation symptoms; the scores were 0, and the total incidences of corneal staining were 3% (left) and 1% (right), respectively. There was no significant difference between the two groups (P > 0.05). Corneal epithelial staining showed single-spot staining, scattered dot, localized, or large areas of fusion staining. No histopathological changes were found in the eyeballs or Hasselblad glands, and the results were evaluated as non-irritative.Conclusion The irregularity of corneal epithelial staining in rabbits did not influence the results of the ocular irritation test.
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Objective To evaluate the effects of intraperitoneal injection of sodium iodate on the physiological indexes and retinal histopathological characteristics of SD rats comprehensively. Methods A total of 64 rats were randomly divided into negative control group and model group, half male and half female. The model group was intraperitoneally injected with 6 mg/mL sodium iodate once at the dose of 10 mL/kg and the negative control group was injected with 10 mL/kg 0.9% NaCl once. The body weight of all surviving rats was detected on the day of injection (0 day) and the 2nd, 6th, 9th, 13th, 16th, 20th, 23rd, 27th, 29th, 36th, 43rd, 50th and 57th days after injection. On the 3rd, 7th, 21st, 28th, 41st and 62nd days after injection, the rats were randomly selected (12 rats in each group on the 28th day, and 4 rats in each group at other time points, those in each group were half male and half female) for serum biochemical indexes detection. The organs were dissected and weighed, and then the main organs and tissues were stained with HE, and the eyes were stained with HE and TUNEL. Blood routine indexes were detected on the 28th and 62nd day after injection. Results After injection of sodium iodate, 88% of the rats in the model group had transient loose stools. During the observation period, the body weight of the rats increased slightly and was more obvious in male rats. On the 28th day after injection, compared with the negative control group, the red blood cell volume (RDW) of female rats and blood urea nitrogen (BUN), reticulocyte count (Retic#) and reticulocyte percentage (Retic%) of male rats in the model group increased significantly (all P<0.05). The white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and hematocrit (HCT) of male and female rats showed decreasing trends, but there were no significant differences between the two groups (all P >0.05). The thymus weight and coefficient of male rats in the model group were smaller than those in the negative control group except for the 7th day after injection, but there were no significant differences between the two groups (all P >0.05). Histopathological examination showed that the retina of the model group gradually developed from wavy changes to abnormal electrocardiogram (ECG)-like changes, with disordered arrangement of each layer, focal thinning of the outer nuclear layer, and apoptosis of the outer nuclear layer of the retina. The incidence of lesions, lesion score and the number of apoptotic cells in the model group were significantly higher than or more than those in the negative control group at the same time, and the difference between the groups on the 28th day was statistically significant (all P<0.01). Conclusion In addition to retinal degeneration in rats, intraperitoneal injection of sodium iodate also had a certain degree of influence on serum biochemical and blood routine indexes, and also showed a slight slow growth of body weight and transient changes in fecal traits. Therefore, when using this model to evaluate drug safety, the effects of modeling reagents on animals should be paid to attention.
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Objective To develop two multi-dimensional value evaluation index systems for intraocular lens(IOL)to assist decision makers in selecting appropriate IOLs.Methods IOL value assessment indexes were determined preliminarily through literature research and expert consultation,and the weights of the indexes were calculated through hierarchical analysis method and then ranked to form two evaluation index systems.Results Two multi-dimensional value evaluation index systems were constructed for monofocal and refractive IOLs respectively,which both contained 3 first-level indicators and 13 second-level indicators;the evaluation index system for monofocal IOL involved in 26 third-level indicators,and the other for refractive IOL had 33 third-level indicators.The three first-level indicators of the two systems were ranked by weight as clinical dimension,economic dimension and institutional dimension.The monofocal IOL evaluation index system had product performance being the second-level indicator with the highest weight,and the top three third-level indicators with the highest weights being lens capsule biocompatibility,risk of intraocular lens damage during implantation and range of applicable populations;the refractive IOL evaluation index system had clinical efficacy(vision)being the second-level indicator with the highest weight,and the top three third-level indicators with the highest weights being distant vision,(astigmatism)rotational stability/postoperative axial rotation and near vision.Conclusion The multi-dimensional value evaluation index systems developed provide references for comprehensive value evaluation of IOLs.[Chinese Medical Equipment Journal,2023,44(11):83-89]
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Objective:To analyze the clinical and laboratory characteristics of mpox patients in Guangzhou City.Methods:The general conditions, symptoms and signs, and laboratory test results of mpox patients admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from June 8 to June 21, 2023 were collected. The clinical characteristics of human immunodeficiency virus (HIV)-infected patients and HIV-negative patients were compared.Independent sample t test, Mann-Whitney U test and Fisher exact probability method were used for statistical analysis. Results:Nineteen mpox patients were included in this study, none of them had been vaccinated with smallpox vaccine. All of them were identifed as gay men with an age of (33.2±6.4) years. And all of them had sex with men within 21 days of onset. There were eight cases with HIV infection and syphilis, respectively. All of these 19 patients had skin lesions which were the first symptom of 15 patients, and appeared during the course of the disease of four patients. Other common symptoms and signs were lymph node enlargement (17 cases), lymph node tenderness (15 cases), pharyngeal congestion (15 cases), tonsil enlargement (13 cases), fever (11 cases) and pruritus (10 cases). There were 13 cases with elevated CD8 + T lymphocytes, interleukin-10 level and procalcitonin level, respectively, 12 cases with elevated serum amyloid A level, and seven cases with elevated blood lymphocyte count. Eight patients were infected with HIV, including one acute infection and seven chronic infections (all of them had received regular antiviral therapy and had a CD4 + T lymphocyte count of 657(400, 757)/μL before onset). There were no significant differences in age ( t=1.55), incidence of complications (Fisher exact probability method), number of skin lesions ( Z=-0.21), incidence of lymph node enlargement (Fisher exact probability method), incidence of fever (Fisher exact probability method), duration of fever ( Z=-0.48), lymphocyte count ( t=-1.55), CD4 + T lymphocyte count ( Z=-0.17) and CD8 + T lymphocyte count ( Z=-1.49) between the HIV-infected patients and HIV-negative patients (all P>0.05). The number of skin lesions was 19(6, 26), and the locations of skin lesions were mainly in perineum and nearby areas (17 cases). The most frequent morphology of skin lesions at admission were papules (15 cases), eschar (15 cases) and pustules (12 cases). All patients recovered after topical medication and symptomatic treatment. Conclusions:Mpox mainly occurs in young and middle-aged men who have sex with men in Guangzhou City. Skin lesions, lymph node enlargement accompanied by tenderness, pharyngeal congestion, tonsil enlargement and fever are the most common features. Common laboratory abnormities are elevated inflammatory markers. The clinical characteristics of HIV-infected patients with normal immune function are similar to those of HIV-negative patients.
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Objective:To explore the effectiveness of artificial intelligent (AI) quality control system on the standard mid-sagittal view of fetal face in 11-13 +6 weeks of gestation. Methods:The quality of the images was evaluated using online " Intelligent ultrasonic quality control system" for 1 063 sections of fetal Nuchal translucency ultrasound images in the Ultrasound Department of Shenzhen Maternity and Child Healthcare Hospital of Southern Medical University. The manual quality control results and time consuming of two experts were compared with AI. The gold standard was decided by experts group with higher seniority.Results:The overall standard rate, substandard rate and nonstandard rate of the image evaluated by the intelligent quality control system was 87.3%, 2.82%, and 9.88%. The overall accuracy of images was 96.6%. The coincidence rates between AI and the two experts were 96.1% and 96.3%, respectively, with strong consistency (Kappa were 0.835 and 0.845 respectively). The time required for intelligent quality control was significantly shorter than manual quality control (208 s vs 6 696 s/6 602 s). All the differences were statistically significant ( Z=-3.981, P<0.001). Conclusions:The intelligent quality control system could accurately and quickly evaluate whether the mid-sagittal view of fetal face in 11-13 +6 weeks of gestation is standard.
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Objective:To develop an artificial intelligence (AI) quality control model of fetal heart in the first trimester and verify its effectiveness.Methods:A total of 18 694 images of the four-chamber view(4CV) and three-vessel and tracheal view(3VT) of fetal heart in the first trimester were selected from Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University since January 2022 to December 2022. A total of 14 432 images were manually annotated. The one-stage target detection algorithm YOLO V5 was used to train the AI quality control model in the first trimester of fetal heart, and 4 262 images (golden standard set by expert group) were used to evaluate the application effectiveness of AI quality control model. Kappa consistency test was used to compare the results of section classification and standard degree judgment from AI quality control model, Doctor 1(D1) and Doctor 2(D2).Results:①Precision of the AI quality control model was 0.895, recall was 0.852, mean average precision (mAP 50) was 0.873.The average precision(AP) of the AI quality control model for section classification was 0.907 (4CV) and 0.989 (3VT), respectively. ②Compared with the gold standard, the overall coincidence rate and consistency of section classification of AI quality control model, D1 and D2 were 99.91% (Kappa=0.998), 100% (Kappa=1.000), 100% (Kappa=1.000), respectively. The coincidence rate and consistency of the plane standard degree evaluation from the AI quality control model, D1 and D2 were 97.46% (Weighted Kappa=0.932), 93.73% (Weighted Kappa=0.847), and 93.12% (Weighted Kappa=0.832), respectively. Strong consistency was displayed. Moreover, AI quality control model showed the highest coincidence rate and the strongest consistency in judging section standard degree, which was superior to manual quality control. The time-consuming of AI quality control (0.012 s/sheet) was significantly less than the way of manual quality control (4.76-6.11 s/sheet)( Z=-8.079, P<0.001). Conclusions:The use of artificial intelligent fetal heart quality control model in the first trimester can effectively and accurately control the image quality.
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This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.
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Humans , Stomach Neoplasms/genetics , Tumor Suppressor Protein p53 , Network Pharmacology , ErbB Receptors , Protein Serine-Threonine Kinases , Serine , Adenosine Triphosphate , Molecular Docking Simulation , Drugs, Chinese Herbal/pharmacologyABSTRACT
AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P<0.05). Total higher-order aberration, horizontal coma and vertical coma showed no significant difference before and after operation(P>0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P<0.05). Under photopic state, the contrast sensitivity of 3.0 and 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05). Under scotopic state, the contrast sensitivity of 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05); there was no significant difference in CCT, K, or intraocular pressure before and after operation(P>0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.
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Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.
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Humans , Choline/metabolism , Phosphatidylcholines/metabolism , Central Nervous System/metabolismABSTRACT
Geopolymer materials are used as construction materials due to their lower carbon dioxide (CO2) emissions compared with conventional cementitious materials. An example of a geopolymer material is alkali-activated kaolin, which is a viable alternative for producing high-strength ceramics. Producing high-performing kaolin ceramics using the conventional method requires a high processing temperature (over 1200 °C). However, properties such as pore size and distribution are affected at high sintering temperatures. Therefore, knowledge regarding the sintering process and related pore structures on alkali-activated kaolin geopolymer ceramic is crucial for optimizing the properties of the aforementioned materials. Pore size was analyzed using neutron tomography, while pore distribution was observed using synchrotron micro-XRF. This study elucidated the pore structure of alkali-activated kaolin at various sintering temperatures. The experiments showed the presence of open pores and closed pores in alkali-activated kaolin geopolymer ceramic samples. The distributions of the main elements within the geopolymer ceramic edifice were found with Si and Al maps, allowing for the identification of the kaolin geopolymer. The results also confirmed that increasing the sintering temperature to 1100 °C resulted in the alkali-activated kaolin geopolymer ceramic samples having large pores, with an average size of ~80 µm3 and a layered porosity distribution.
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This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification.