Unique composition of ocular surface microbiome in the old patients with dry eye and diabetes mellitus in a community from Shanghai, China.

BACKGROUND: This study investigates the variations in microbiome abundance and diversity on the ocular surfaces of diabetic patients suffering from dry eye within a community setting. The goal is to offer theoretical insights for the community-level prevention and treatment of dry eye in diabetic cohorts. METHODS: Dry eye screening was performed in the Shanghai Cohort Study of Diabetic Eye Disease (SCODE) from July 15, 2021, to August 15, 2021, in the Xingjing community; this study included both a population with diabetes and a normal population. The population with diabetes included a dry eye group (DM-DE, n = 40) and a non-dry eye group (DM-NoDE, n = 39). The normal population included a dry eye group (NoDM-DE, n = 40) and a control group (control, n = 39). High-throughput sequencing of the 16 S rRNA V3-V4 region was performed on conjunctival swab from both eyes of each subject, and the composition of microbiome on the ocular surface of each group was analyzed. RESULTS: Significant statistical differences were observed in both α and ß diversity of the ocular surface microbiome among the diabetic dry eye, diabetic non-dry eye, non-diabetic dry eye, and normal control groups (P < 0.05). CONCLUSIONS: The study revealed distinct microecological compositions on the ocular surfaces between the diabetic dry eye group and other studied groups. Firmicutes and Anoxybacillus were unique bacterial phyla and genera in the dry eye with DM group, while Actinobacteria and Corynebacterium were unique bacterial phyla and genera in the normal control group.

The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers.

BACKGROUND AND AIMS: Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD). METHODS: The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics. RESULTS: Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (ß = 0.86, P < 0.001) and WBC (ß = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients. CONCLUSION: Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.

Study on the correlation between iris blood flow, iris thickness and pupil diameter in the resting state and after pharmacological mydriasis in patients with diabetes mellitus.

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.

Changes in Life's Essential 8 and risk of cardiovascular disease in Chinese people.

BACKGROUND: The American Heart Association recently released an updated algorithm for evaluating cardiovascular health-Life's Essential 8 (LE8). However, the associations between changes in LE8 score over time and risk of cardiovascular disease (CVD) remain unclear. METHODS: We investigated associations between 6-year changes (2006-12) in LE8 score and risk of subsequent CVD events (2012-20) among 53 363 Chinese men and women from the Kailuan Study, who were free from CVD in 2012. The LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose and blood pressure. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 4281 incident CVD cases during a median of 7.7 years of follow-up. Compared with participants whose LE8 scores remained stable in a 6-year period, those with the large increases of LE8 score over the 6-year period had a lower risk of CVD, heart disease and stroke in the subsequent 8 years [HRs and 95% CIs: 0.67 (0.64, 0.70) for CVD, 0.65 (0.61, 0.69) for heart disease, 0.71 (0.67, 0.76) for stroke, all Ptrend < 0.001]. Conversely, those with the large decreases of LE8 score had 47%, 51% and 41% higher risk for CVD, heart disease and stroke, respectively. These associations were consistent across the subgroups stratified by risk factors. CONCLUSIONS: Improving LE8 score in a short- and moderate-term was associated with a lower CVD risk, whereas decreased LE8 score over time was associated with a higher risk.

Significantly different results in the ocular surface microbiome detected by tear paper and conjunctival swab.

BACKGROUND: Great variation has been observed in the composition of the normal microbiota of the ocular surface, and therefore, in addition to differences in detection techniques, the method of collecting ocular surface specimens has a significant impact on the test results.The goal of this study is to ascertain whether the eye surface microbial communities detected by two different sampling methods are consistent and hence explore the feasibility of using tear test paper instead of conjunctival swabs to collect eye surface samples for microbial investigation. MATERIALS AND METHODS: From July 15, 2021, to July 30, 2021, nonirritating tear test strips and conjunctival swabs of both eyes were used in 158 elderly people (> 60 years old) (79 diabetic and 79 nondiabetic adults) in Xinjing Community for high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The composition of the microbial communities in tear test paper and conjunctival swab samples was analyzed. RESULTS: There was no statistically significant difference in Alpha diversity of ocular surface microorganisms represented by tear strip and conjunctival swab in diabetic group (P > 0.05), but there was statistically significant difference in Alpha diversity of ocular surface microorganisms detected by tear strip and conjunctival swab in nondiabetic group (P < 0.05). There were statistically significant differences in Beta diversity of ocular surface microorganisms detected by two sampling methods between diabetic group and nondiabetic group (P < 0.05). There were statistically significant differences in ocular surface microorganisms detected by tear strip method between diabetic group and nondiabetic group (P < 0.05), but there was no statistically significant difference in conjunctival swab method (P > 0.05). CONCLUSIONS: Tear test paper and conjunctival swabs detect different compositions of microbes through two different techniques of eye surface microbe sampling. Tear test paper cannot completely replace conjunctival swab specimens for the study of microbes related to eye surface diseases.

Metagenomic analysis of microbiological changes on the ocular surface of diabetic children and adolescents with a dry eye.

BACKGROUND: Microbiome changes on the ocular surface may cause dry eyes. A metagenome assay was used to compare the microbiome composition and function of the ocular surface between diabetic children and adolescents with dry eye, diabetic children and adolescents without dry eye, and normal children. MATERIALS AND METHODS: Twenty children and adolescents aged 8 to 16 with diabetes were selected from the Shanghai Children and Adolescent Diabetes Eye Study. Ten healthy children and adolescents belonging to the same age group were selected from the outpatient clinic during the same period. The participants were classified into the dry eye group (DM-DE group, n = 10), the non-dry eye group (DM-NDE group, n = 10) and the normal group (NDM group, n = 10). A conjunctival sac swab was collected for metagenomic sequencing, and the relationship between the microbiome composition and functional gene differences on the ocular surface with dry eye was studied. RESULTS: The classification composition and metabolic function of the microorganisms on the ocular surface of children in the 3 groups were analyzed. It was found that children's ocular microbiota was composed of bacteria, viruses and fungi. There were significant differences in α diversity and ß diversity of microbial composition of ocular surface between DM-DE group and NDM group(P<0.05). There were significant differences in α and ß diversity of metabolic pathways between the two groups(P<0.05). The functional pathways of ocular surface microorganisms in diabetic children with dry eyes were mainly derived from human disease, antibiotic resistance genes, carbohydrate, coenzyme and lipid transport and metabolism-related functional genes; In normal children, the functional pathways were mainly derived from replication, recombination, repair, signal transduction and defense-related functional genes. CONCLUSION: The DM-DE group have unique microbial composition and functional metabolic pathways. The dominant species and unique metabolic pathways of the ocular surface in the DM-DE group may be involved in the pathogenesis of dry eye in diabetic children.

Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease Incidence and Mortality in the United States Men and Women with Diabetes Mellitus.

BACKGROUND: Evidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited. OBJECTIVES: The aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D. METHODS: We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014 and Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality, were assessed using Cox proportional-hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. RESULTS: During 196,955 and 225,371 person-years of follow-up in participants with T2D, there were 2927 incident CVD cases and 4898 deaths, respectively. Higher intake of glutamine was associated with lower risk of CVD incidence, CVD mortality, and total mortality: comparing extreme quintiles, the hazard ratios (HRs) (95% confidence intervals [CIs]) were 0.88 (0.77, 0.99), 0.78 (0.65, 0.92), and 0.84 (0.76, 0.92), respectively (all P-trend < 0.05). In contrast, higher intake of glutamate was associated with a higher risk of CVD incidence, CVD mortality, and total mortality; the HRs were 1.30 (1.15, 1.46), 1.46 (1.24, 1.72), and 1.20 (1.09, 1.32), respectively (all P-trend < 0.05). Furthermore, comparing extreme quintiles, a higher dietary glutamine-to-glutamate ratio was associated with a lower risk of CVD incidence (0.84 [0.75, 0.95]), CVD mortality (0.66 [0.57, 0.77]), and total mortality (0.82 [0.75, 0.90]). In addition, compared with participants with stable or decreased consumption of glutamine-to-glutamate ratio from prediabetes to postdiabetes diagnosis, those who increased the ratio had a 17% (5%, 27%) lower CVD mortality. CONCLUSIONS: In adults with T2D, dietary glutamine was associated with a lower risk of CVD incidence and mortality, whereas the opposite was observed for glutamate intake.

Dietary fruits and vegetables and risk of cardiovascular diseases in elderly Chinese.

BACKGROUND: Evidence regarding the potential effect of fruit and vegetable consumption on cardiovascular diseases (CVD) was limited and inconsistent among Asian people. METHODS: We prospectively examined associations of fruit and vegetable consumption with the risk of CVD among 9740 participants aged 65 years and older (mean baseline age: 88 years) in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (2008-2018). Dietary data were collected using a validated food frequency questionnaire. RESULTS: During 37 366 person-years of follow-up, a total of 3738 CVD cases were recorded. After adjusting for demographics, dietary, lifestyle and economical social factors, higher intakes of total fruits and vegetables were associated with lower risk of CVD [comparing with extreme quintiles, hazard ratio and 95% confidence interval: 0.84 (0.74, 0.95)]. The inverse association was mainly driven by vegetable consumption [0.86 (0.77, 0.95)]. Furthermore, the inverse association was stronger for the risk of hypertension [0.84 (0.72, 0.98)]. These associations were consistent across age, sex, body mass index, residence, exercise status, smoking, drinking, meat intake, modified hPDI and health status. CONCLUSIONS: This study suggests higher intakes of total fruits and vegetables are associated with a lower risk of CVD among elderly Chinese people, supporting the current recommendations of increasing fruit and vegetable consumption as part of a healthy diet for the prevention of CVD.

Discrepancies in Vessel Density and Blood Flow Distribution in Different Areas of the Iris among Pediatric Type 1 Diabetes Mellitus and Adult Type 2 Diabetes Mellitus Patients.

INTRODUCTION: Diabetes mellitus may compromise the vasculature of the iris, thereby leading to severe vision-threatening complications. This study aimed to investigate differences in iris blood flow indices between pediatric type 1 diabetes mellitus (T1DM) patients and adult type 2 diabetes mellitus (T2DM) patients. METHODS: This was a cross-sectional study. Pediatric T1DM patients and healthy children were members of the Shanghai Children and Adolescent Diabetes Eye (SCADE) cohort who visited Shanghai Eye Hospital in February 2022. The adult T2DM patients and healthy adults were patients who visited Shanghai General Hospital from October 2021 to January 2022. Iris OCTA was acquired through a Cirrus HD-OCT 5000 angiography system (Carl Zeiss Meditec, Inc.). A unique iris OCTA quantification method was used, and the vessel area density (VAD) and vessel skeleton density (VSD) were obtained. The area from the pupillary margin to the corneoscleral limbus was taken as the whole iris blood flow index, and the inner third near the pupillary margin of the whole iris was taken as the pupillary margin blood flow index. RESULTS: This study enrolled 34 pediatric T1DM patients, 34 age-matched healthy children, 34 adult T2DM patients, and 34 age-matched healthy adults. The whole iris and pupillary margin VAD and VSD of the pediatric T1DM patients were not different from those of healthy children. The whole iris VAD and VSD of the adult T2DM patients were lower than those of healthy adults, and the pupillary margin VAD and VSD were the same in these two groups. Compared with adult T2DM patients, pediatric T1DM patients had higher whole iris VAD and VSD and lower pupillary margin VAD and VSD values, all with statistical significance. Among diabetic patients, age, BMI, and glycated hemoglobin level were negative independent influencing factors for whole iris VAD and VSD, and age was a positive influencing factor for pupillary margin VAD and VSD. CONCLUSION: There are diverse alterations in iris vessel density and blood flow distribution between pediatric T1DM patients and adult T2DM patients.

Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989-1993, 2000-2001, 2006-2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose-response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose-response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645.

Plant-based Diet and Adiposity Over Time in a Middle-aged and Elderly Population: The Rotterdam Study.

BACKGROUND: We aimed to explore whether adhering to a more plant-based diet, beyond strict vegan or vegetarian diets, may help prevent adiposity in a middle-aged and elderly population. METHODS: We included 9,633 participants from the Rotterdam Study, a prospective cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline of three subcohorts of the Rotterdam Study (1989-1993, 2000-2001, 2006-2008). We created a plant-based diet index by giving plant-based foods positive scores and animal-based foods reverse scores. A higher score on the index reflected an overall more plant-based and less animal-based diet. Data on anthropometrics and body composition (using dual energy X-ray absorptiometry) were collected every 3-5 years from 1989 to 2016. We used multivariable linear mixed models to analyze the associations. RESULTS: In the 9,633 participants, baseline plant-based diet score ranged from 21.0 to 73.0 with a mean ± SD of 49.0 ± 7.0. In multivariable-adjusted analyses, higher adherence to a plant-based diet was associated with lower BMI, waist circumference, fat mass index, and body fat percentage across a median follow-up period of 7.1 years (per 10 points higher score, BMI: ß = -0.70 kg/m [95% CI = -0.81, -0.59]; waist circumference: -2.0 cm [-2.3, -1.7]; fat mass index: -0.66 kg/m [-0.80, -0.52]; body fat percentage: -1.1 points [-1.3, -0.84]). CONCLUSIONS: In this population-based cohort of middle-aged and elderly participants, a higher adherence to a more plant-based, less animal-based diet was associated with less adiposity over time, irrespective of general healthfulness of the specific plant- and animal-based foods.

Plant versus animal based diets and insulin resistance, prediabetes and type 2 diabetes: the Rotterdam Study.

Vegan or vegetarian diets have been suggested to reduce type 2 diabetes (T2D) risk. However, not much is known on whether variation in the degree of having a plant-based versus animal-based diet may be beneficial for prevention of T2D. We aimed to investigate whether level of adherence to a diet high in plant-based foods and low in animal-based foods is associated with insulin resistance, prediabetes, and T2D. Our analysis included 6798 participants (62.7 ± 7.8 years) from the Rotterdam Study (RS), a prospective population-based cohort in the Netherlands. Dietary intake data were collected with food-frequency questionnaires at baseline of three sub-cohorts of RS (RS-I-1: 1989-1993, RS-II-1: 2000-2001, RS-III-1: 2006-2008). We constructed a continuous plant-based dietary index (range 0-92) assessing adherence to a plant-based versus animal-based diet. Insulin resistance at baseline and follow-up was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Prediabetes and T2D were collected from general practitioners' records, pharmacies' databases, and follow-up examinations in our research center until 2012. We used multivariable linear mixed models to examine association of the index with longitudinal HOMA-IR, and multivariable Cox proportional-hazards regression models to examine associations of the index with risk of prediabetes and T2D. During median 5.7, and 7.3 years of follow-up, we documented 928 prediabetes cases and 642 T2D cases. After adjusting for sociodemographic and lifestyle factors, a higher score on the plant-based dietary index was associated with lower insulin resistance (per 10 units higher score: ß = -0.09; 95% CI: - 0.10; - 0.08), lower prediabetes risk (HR = 0.89; 95% CI: 0.81; 0.98), and lower T2D risk [HR = 0.82 (0.73; 0.92)]. After additional adjustment for BMI, associations attenuated and remained statistically significant for longitudinal insulin resistance [ß = -0.05 (- 0.06; - 0.04)] and T2D risk [HR = 0.87 (0.79; 0.99)], but no longer for prediabetes risk [HR = 0.93 (0.85; 1.03)]. In conclusion, a more plant-based and less animal-based diet may lower risk of insulin resistance, prediabetes and T2D. These findings strengthen recent dietary recommendations to adopt a more plant-based diet.Clinical Trial Registry number and website NTR6831, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 .

Ultraprocessed foods, unprocessed or minimally processed foods, and risk of frailty in a cohort of United States females.

BACKGROUND: Ultraprocessed foods (UPFs) and poor diet quality have been associated with frailty but existing studies had relatively short follow-up time. It is also unclear whether the association of UPF was primarily due to its correlation with poorer diet quality. OBJECTIVES: We examined the association between unprocessed or minimally processed foods (UMFs) and UPF and risk of frailty and explored whether the association with UPF was mainly driven by poor diet quality. METHODS: In total, 63,743 nonfrail females aged 60+ y from the Nurses' Health Study (cohort study) were followed up for ≥26 y. Diet was assessed every 4 y by food frequency questionnaires. UPF and UMF intakes were calculated using the Nova classification. Diet quality was estimated using the Alternate Healthy Eating Index (AHEI) 2010. The association of UMF and UPF with risk of frailty was examined using multivariable adjusted Cox proportional hazard model. RESULTS: During the follow-up period, we recorded 15,187 incident cases of frailty. The hazard ratio (HR) of frailty for the highest compared with the lowest quintile of UMFs (servings per day) was 0.86 (95% CI: 0.83, 0.95; P-trend < 0.001). However, this was no longer statistically significant after adjustment for AHEI-2010. UPFs (servings per day) was directly associated with risk of frailty, even after adjustment for AHEI-2010 (1.31; 95% CI: 1.23, 1.39; P-trend < 0.001). Among those at the highest category of the AHEI-2010, UPFs remained directly associated with frailty (HR comparing top with bottom quintile: 1.40; 95% CI:1.24, 1.57; P-trend < 0.001). For UPF components, we found a higher frailty risk with each serving per day of artificial and sugar-sweetened beverages; fat, spreads, and condiments; yogurt and dairy-based desserts; and other UPFs. However, processed whole grains were not associated with frailty. CONCLUSIONS: Higher intake of UPF is associated with a higher risk of frailty in older females. This is not explained by a lower diet quality contributed by UPFs.

[Construction of RNAi vector of dopamine D1 receptor and identification of its silencing effects].

OBJECTIVE: To construct dopamine D1 receptor (DRD1) expression interference vectors to study the role of DRD1 in nerve cells and lay a foundation for drug development in anti-convulsion. METHODS: Based on DRD1 gene sequence in GenBank, 10 interfere vectors of DRD1 were designed. Liposomal was used to transfect NG-108-15 and the transfect effect was assayed by GFP. With realtime PCR and Western blot, the DRD1 expression was detected. RESULTS: The 10 constructed interfere vectors transfected into NG-108-15 cells by liposomal method and inhibited DRD1 mRNA and protein expression. DRD1 mRNA expression in NG-108-15 cells transfected with pGPU6-GFP-Neo-si-DRD1-5 was the lowest whereas DRD1 protein expression in NG-108-15 cells transfected with pGPU6-GFP-Neo-si-DRD1-1, -2, -6, -7 was the lowest. CONCLUSION: DRD1 expression interference vector is successfully constructed.

A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022.

Background: Since the approval of the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for marketing in 2015, PCSK9 inhibitors have attracted significant interest in the field of cardiovascular endocrinology. A large number of clinical trials have confirmed the efficacy and safety of PCSK9 inhibitors in reducing cholesterol and the risk of cardiovascular events. No bibliometric analysis of PCSK9 inhibitors has been performed as of yet. This study aims to analyze the research trends and hotspots of PCSK9 inhibitors through bibliometric analysis. Methods: We searched the Web of Science Core Collection (WoSCC) database for PCSK9 inhibitor-related publications from 2007 to 2022. Data visualization analysis was performed using CiteSpace software. Microsoft Excel and Graphpad software were used for the drawing of some tables and figures. Results: A total of 1072 pieces of literature were retrieved between 2007 and 2022. The number of publications concerning PCSK9 inhibitors is growing annually. The top five countries with the most articles published were the United States, England, Canada, Italy, and France. Harvard University, Amgen, Brigham & Women's Hospital, Harvard Medical School, and Imperial College London are the five institutions with the highest output. The Journal of Clinical Lipidology is the most popular journal in this field. The most frequently cited journal is the New England Journal of Medicine. As for authors, Sabatine MS and Giugliano RP from Brigham & Women's Hospital have the highest number of published articles. Amgen is the funding agency for most of the research. According to keyword analysis, "low density lipoprotein", "familial hypercholesterolemia", "PCSK9 inhibitor", "PCSK9", and "efficacy" are the five keywords with the highest frequency of co-occurrence. Conclusion: The past 15 years have witnessed a rapid and fruitful development of PCSK9 inhibitors. The research trend and focus for PCSK9 inhibitors are from the mechanism of reducing low-density lipoprotein cholesterol to related clinical trials. Developed countries such as the United States have contributed prominently in this area. Coronary artery and inflammation are currently at the forefront of research in the field and are in an explosion period.

Association of circulating vitamin D and omega 3 fatty acid with all-cause mortality in patients with rheumatoid arthritis: A large population-based cohort study.

OBJECTIVES: To assess the associations of both the level of circulating vitamin D and the ratio of omega-3 fatty acids to total fatty acids (omega-3 %) with mortality among participants with rheumatoid arthritis. STUDY DESIGN: This study included 4,293 and 1,157 adults with rheumatoid arthritis identified by self-report from the UK Biobank for the analysis of vitamin D and omega-3 %, respectively. MAIN OUTCOME MEASURES: Death outcomes were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland). Cox proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for mortality. RESULTS: The medians (25th-75th percentiles) of serum 25(OH)D and omega-3 % were 45.8 (31.4-62.9) nmol/L and 4.1 % (3.3 %-5.1 %), respectively. During 52,612 person-years of follow-up in the 25(OH)D group, 502 all-cause deaths occurred; and during 14,192 person-years of follow-up in the omega-3 % group, 122 all-cause deaths occurred. Rheumatoid arthritis patients with vitamin D levels of at least 20 nmol/L had an approximately 40-50 % lower risk of all-cause mortality than those with severe vitamin D deficiency (hazard ratio ranging from 0.51 to 0.62, all P values < 0.05). Each unit increase in natural log-transformed 25(OH)D was associated with a 22 % reduction in the risk of all-cause mortality, and a U-shaped association between serum 25(OH)D and all-cause mortality was found. However, the association between omega-3 % and mortality was not significant. CONCLUSIONS: Lower serum 25(OH)D concentration, but not omega-3 %, was significantly associated with higher all-cause mortality in patients with rheumatoid arthritis. Optimizing serum vitamin D levels may be an important factor in reducing mortality risk in this population.

Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies.

BACKGROUND: Evidence regarding dietary phytoestrogens in relation to mortality remains limited. OBJECTIVES: The objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females. METHODS: We followed 75,981 females in the Nurses' Health Study (1984-2018) and 44,001 males in the Health Professionals Follow-up Study (1986-2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history. RESULTS: During 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality. CONCLUSIONS: A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

Ultra-Processed Food Consumption and Risk of Type 2 Diabetes: Three Large Prospective U.S. Cohort Studies.

OBJECTIVE: We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality. RESEARCH DESIGN AND METHODS: We included 71,871 women from the Nurses' Health Study, 87,918 women from the Nurses' Health Study II, and 38,847 men from the Health Professional Follow-Up Study. Diet was assessed using food frequency questionnaires and UPF was categorized per the NOVA classification. Associations of total and subgroups of UPF with T2D were assessed using Cox proportional hazards models. We subsequently conducted a meta-analysis of prospective cohort studies on total UPF and T2D risk, and assessed meta-evidence quality using the NutriGrade scoring system. RESULTS: Among the U.S. cohorts (5,187,678 person-years; n = 19,503 T2D cases), the hazard ratio for T2D comparing extreme quintiles of total UPF intake (percentage of grams per day) was 1.46 (95% CI 1.39-1.54). Among subgroups, refined breads; sauces, spreads, and condiments; artificially and sugar-sweetened beverages; animal-based products; and ready-to-eat mixed dishes were associated with higher T2D risk. Cereals; dark and whole-grain breads; packaged sweet and savory snacks; fruit-based products; and yogurt and dairy-based desserts were associated with lower T2D risk. In the meta-analysis (n = 415,554 participants; n = 21,932 T2D cases), each 10% increment in total UPF was associated with a 12% (95% CI 10%-13%) higher risk. Per NutriGrade, high-quality evidence supports this relationship. CONCLUSIONS: High-quality meta-evidence shows that total UPF consumption is associated with higher T2D risk. However, some UPF subgroups were associated with lower risk in the U.S. cohorts.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. RESEARCH QUESTION: What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH?. STUDY DESIGN AND METHODS: A total of 135 age- and BMI-matched patients with PAH and 49 control subjects were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. RESULTS: Compared with the control subjects, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8 mL vs 3.5 ± 0.7 mL; P = .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear = .001), right ventricular end-diastolic volume index (P < .001), right ventricular cardiac output (P = .003), N-terminal pro-brain natriuretic peptide (P = .030), and the risk of clinical worsening (P = .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95% CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95% CI, 1.5-30.2) for high-level EATV in patients with PAH. INTERPRETATION: Patients with PAH had a decreased EATV compared with control subjects. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

Two-year longitudinal study on changes in thickness of the retinal nerve fiber layer and ganglion cell layer in children with type 1 diabetes mellitus without visual impairment or diabetic retinopathy.

PURPOSE: To study changes in the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) in children with type 1 diabetes mellitus (T1DM) without visual impairment or diabetic retinopathy (DR) after 2 years of follow-up and analyze the associated factors. METHODS: Thirty-seven children with T1DM were enrolled in this study. All children underwent a complete ophthalmologic evaluation that included swept-source optical coherence tomography at baseline and follow-up. Changes in RNFL and GCL thickness were compared among the children at baseline and follow-up. RESULTS: The peripapillary RNFL thickness was greater in the temporal (inner, p = 0.015; outer, p = 0.004) and inner superior (p = 0.043) sectors in the follow-up group than in the baseline group. The macular RNFL thickness in the fovea, inner nasal sector, inner inferior sector, and outer ring and the average thickness (all p < 0.05) were greater in the follow-up group than in the baseline group. The peripapillary GCL thickness decreased in the temporal sector (inner, p = 0.049; outer, p = 0.041) and increased in the inner nasal sector (p = 0.006) in the follow-up group compared with the baseline group, and the thickness of the inner temporal, inner superior, inner inferior, outer nasal, and outer inferior sectors and average thickness in the macula were lower in the follow-up group than in the baseline group (all p < 0.05). The total retinal thickness around optic disc in the follow-up group increased in the inner superior sectors (p = 0.006). The total retinal thickness of the macula decreased in inner temporal sector, inner superior sector and outer nasal sector, and increased in outer superior sector (all p < 0.05). CONCLUSIONS: Retinal neurodegenerative changes preceded microvascular changes in children with T1DM in the early stage. Peripapillary RNFL thickness in the nasal sector may be lower in children with T1DM without visual impairment or other ocular pathologies.