Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Objective To investigate the efficacy of Lactobacillus plantarum ZG03(L.plantarum ZG03)for ameliorating oxidative stress in zebrafish.Methods We evaluated the growth pattern of L.plantarum ZG03,observed its morphology using field emission scanning electron microscopy,and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis.FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish.In a zebrafish model of 2%glucose-induced oxidative stress,the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue(CHT),superoxide dismutase(SOD)activity,reactive oxygen species(ROS)levels,and malondialdehyde(MDA)content.Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids(SCFAs)in the zebrafish,and the antioxidant effects of the key metabolites(acetate,propionate,and caproate)were tested.Results On MRS agar,L.plantarum ZG03 formed circular,smooth,moist,and milky-white colonies with a rod-shaped cell morphology.Genomic analysis revealed abundant sugar metabolism gene clusters.After inoculation of FITC-labeled L.plantarum ZG03 in zebrafish,green fluorescence was clearly observed in the intestinal bulb,mid-intestine,and hind intestine.In zebrafish with glucose-induced oxidative stress,L.plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity.L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid,propionic acid,and caproic acid in zebrafish metabolites.In addition,sodium acetate,sodium propionate,and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models.Conclusion L.plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites,particularly the SCFAs including acetic acid,propionic acid and caproic acid.

OBJECTIVE: To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 (CYP19A1) gene with risk of Breast cancer. METHODS: Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No. 2021-182). RESULTS: No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups (P > 0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group (P < 0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages III-IV were significantly higher than those at stage I-II (P < 0.05). CONCLUSION Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
Humans ; Female ; Breast Neoplasms/genetics* ; Aromatase/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Middle Aged ; Genetic Predisposition to Disease ; Adult ; Genotype ; Case-Control Studies ; Alleles ; Gene Frequency ; Risk Factors ; Aged

Objective:To investigate the impact of different CT reconstruction kernels on the quantitative analysis of small pulmonary vessels in patients with chronic obstructive pulmonary disease (COPD) and high-risk patients.Methods:This study was a cross-sectional study. Clinical and imaging data of 73 COPD and high-risk patients visiting the China-Japan Friendship Hospital between March and April 2024 were retrospectively analyzed. All patients underwent high-resolution CT of the chest and pulmonary function tests, with the ratio of forced expiratory volume in one second to forced vital capacity (FEV 1/FVC) obtained. The raw CT data were reconstructed using different kernels: the FC86 group used the adaptive iterative dose reduction(AIDR) 3D standard lung sharp reconstruction algorithm, the FC18 group used the AIDR 3D standard Body standard reconstruction algorithm, the advanced intelligent clear-IQ engine(AiCE) Lung group used the AiCE deep learning reconstruction algorithm for lung, and the AiCE Body group used the AiCE deep learning reconstruction algorithm for body. Image signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise were calculated. The pulmonary vessel segmentation & Measurement software was used to segment and extract pulmonary arteries and veins of four groups in thin-slice whole-lung CT imaging, obtaining the ratio of small pulmonary arteries (%V artery<5) and the ratio of small pulmonary veins (%V vein<5). The One-way repeated measures ANOVA or Friedman test was used to compare the differences in SNR, CNR, image noise, %V artery<5, and %V vein<5 among the four groups, followed by Bonferroni post hoc or Bonferroni-Dunn test with P-value correction to analysis differences between subgroups. The correlations between %V artery<5 and FEV 1/FVC, as well as between %V vein<5 and FEV 1/FVC were analyzed using Spearman rank correlation analysis in all four groups. Results:The overall differences in image noise, SNR, and CNR in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). Except for the difference in CNR values between the AiCE Lung group and the FC18 group, which was not statistically significant ( P=0.192), all differences were statistically significant ( P<0.016 7). The overall differences in %V artery<5 values and %V vein<5 values in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). The %V artery<5 and %V vein<5 values in the FC18 group were lower than those in the AiCE Lung, AiCE Body, and FC86 groups ( P<0.016 7), and the rest of the differences were not statistically significant ( P>0.016 7). %V artery<5 and %V vein<5 were positively correlated with FEV 1/FVC in all 4 groups ( P<0.05), with the highest correlation coefficient between %V vein<5 and FEV 1/FVC in the AiCE Body group ( r=0.501, P=0.001). Conclusions:DLR-AiCE-based kernel reconstruction optimizes image quality and significantly affects the results of quantitative parameters of small pulmonary vessels. The reconstruction kernel prioritized for quantitative analysis of small vessels within the lungs in COPD based on the CT scanner in this study is AiCE Body.

Objective:To establish a combined model of tumor heterogeneity metabolic parameters using 18F-FDG PET/CT and explore its value in differentiating benign from malignant pulmonary lesions. Methods:A total of 251 patients (157 males, 94 females; age 15-88 years) who were diagnosed with malignant lung lesions by 18F-FDG PET/CT and with definitive pathological results at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2017 to February 2024 were retrospectively enrolled. Analysis was conducted on clinical data, traditional parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of primary lesions on 18F-FDG PET/CT, and intra-tumoral metabolic heterogeneity index (HI; such as cumulative SUV volume histogram AUC (AUC-CSH), linear regression slope, CV). AUC-CSH and CV were calculated using SUV thresholds of 2.5 and 40%SUV max. Logistic univariate and multivariate regression analyses were used to extract independent predictors in clinical features and PET/CT parameters for the differential diagnosis of pulmonary lesions. A multi-parameter combined model was established through logistic regression and validated for diagnostic efficacy using ROC curve analysis. Results:Among 251 patients, 101 were benign and 150 were malignant. In univariate analysis, gender, age, tumor markers, spiculation sign, lobulation sign, vessel convergence sign, air bronchogram, long diameter, short diameter, SUV max, AUC-CSH 2.5, AUC-CSH 40%, CV2.5, and CV40% were predictive factors for the diagnosis of benign and malignant tumors (odds ratio ( OR): 0.57-17.39, all P<0.05). In multivariate analysis, gender, age, tumor markers, lobulation sign, vessel convergence sign, SUV max, AUC-CSH 40%, and CV40% were independent predictors for the diagnosis of benign and malignant tumors ( OR: 2.30-13.18, all P<0.05). The AUC, sensitivity, specificity, and accuracy of the multi-parameter combined model established with the above independent predictors were 0.89, 77.33%(116/150), 84.16%(85/101), 80.08%(201/251), respectively. Conclusion:18F-FDG PET/CT multi-parameter combined model has high value in the differentiation of benign and malignant pulmonary lesions.

Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.

Objective:To investigate the correlation between thyroid function and the total cerebral small vessel disease score in the elderly.Methods:This cross-sectional study included elderly people who underwent physical examinations at the Geriatrics Department of Beijing Hospital from April 2019 to December 2020. Participants were devided into 5 groups based on the total score of cerebral small vessel disease: 0, 1, 2, 3, and 4. General clinical data were collected through physical examination reports and outpatient medical records. All participants underwent a 3T brain magnetic resonance imaging (MRI), scan and data were collected to calculate the total cerebral small vessel disease score. Fasting venous blood samples were taken in the morning to measure thyroid hormone levels. Relationships between thyroid hormone levels and lacunar infarcts, microbleeds, white matter hyperintensities (WMH), enlarged perivascular spaces, and total cerebral small vessel disease score were analyzed using Spearman correlation. Multivariate ordinal logistic regression was also used to analyze factors associated with total cerebral small vessel disease score.Results:A total of 545 elderly individuals were included, with a mean age of (75.16±9.18) years, and 505 (92.7%) were male. The number of subjects with a total cerebral small vessel disease score of 0 were 207 (38.0%), 1 were 182 (33.4%), 2 were 99 (18.2%), 3 were 41 (7.5%), and 4 were 16 (2.9%). Statistical significant differences were found in age, fasting blood glucose, systolic blood pressure, triiodothyronine (TT3), free triiodothyronine (FT3), and the proportion of hypertensive patients among the groups (all P<0.05). Spearman correlation analysis showed that TT3 ( r=-0.138, P=0.001) and FT3 ( r=-0.213, P<0.001) were negatively correlated with total cerebral small vessel disease score. Multivariate ordinal logistic regression analysis revealed that age was independently and positively associated with total cerebral small vessel disease score ( OR=1.139, 95% CI: 1.087-1.193, P<0.001), while FT3 was independently and negatively associated with total cerebral small vessel disease score ( OR=0.331, 95% CI: 0.118-0.929, P=0.009). Conclusion:In the elderly population, FT3 levels are independently and negatively associated with total cerebral small vessel disease score.

Objective:To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 ( CYP19A1) gene with risk of breast cancer. Methods:Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No.2021-182). Results:No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups ( P>0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group ( P<0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages Ⅲ-Ⅳ were significantly higher than those at stage Ⅰ-Ⅱ ( P<0.05). Conclusion:Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.

Objective:To establish a rapid and accurate duplex real-time fluorescent reverse transcription-recombinase polymerase amplification/recombinase-aided amplification（RT-RPA/RAA）detection method for identification and differentiation of Nipah virus（NiV），Langya virus（LayV），Mojiang virus（MoJV），and Cedar virus（CedV）.Methods:First，specific primers and probes were designed targeting the conserved L gene regions of NiV and LayV，as well as the conserved N gene regions of MoJV and CedV，respectively. The four viruses were divided into two groups for duplex detection. Subsequently，the optimal primer and probe combinations were screened by comparing the amplification efficiency of different primer pair combinations（F1/R1，F1/R2，F2/R1，F2/R2）. The reaction temperature was optimized through temperature gradient settings from 37 ℃ to 42 ℃，and the amounts of primers and probes were optimized to establish the duplex real-time fluorescent RT-RPA/RAA detection system. Finally，the detection performance was evaluated through specificity，sensitivity，and stability tests，as well as clinical sample validation.Results:The selected primer pairs（NiV primer pair F2/R1，LayV primer pair F1/R1，MoJV primer pair F2/R2，and CedV primer pair F2/R2）all demonstrated optimal amplification efficiency when combined with their corresponding probes. The optimal annealing temperature was 39 ℃，and the minimum detection limit was 101-102 copies/μl. The method could effectively distinguish target viruses from other non-target viruses，and repeated experiments showed good stability（ R2> 0.90）. Additionally，detection results for Malaysian NiV strains and various clinical samples were consistent with the Taqman multiplex qRT-PCR method. Conclusion:The duplex real-time fluorescent RT-RPA/RAA detection method successfully established in this study can rapidly and accurately identify and differentiate four important henipavirus-like viruses：NiV，LayV，MoJV，and CedV. It features simple operation，rapid reaction，high specificity，and good stability，providing an effective molecular detection tool for rapid field diagnosis，surveillance，and control of these zoonotic viruses.

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors