Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study.

OBJECTIVE: To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population. DESIGN: A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled. SETTING AND PARTICIPANTS: Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed. ANALYSIS AND OUTCOME MEASURES: Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4+ T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated. RESULTS: Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response. CONCLUSIONS: Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.

Construction and validation of machine learning algorithm for predicting depression among home-quarantined individuals during the large-scale COVID-19 outbreak: based on Adaboost model.

OBJECTIVES: COVID-19 epidemics often lead to elevated levels of depression. To accurately identify and predict depression levels in home-quarantined individuals during a COVID-19 epidemic, this study constructed a depression prediction model based on multiple machine learning algorithms and validated its effectiveness. METHODS: A cross-sectional method was used to examine the depression status of individuals quarantined at home during the epidemic via the network. Characteristics included variables on sociodemographics, COVID-19 and its prevention and control measures, impact on life, work, health and economy after the city was sealed off, and PHQ-9 scale scores. The home-quarantined subjects were randomly divided into training set and validation set according to the ratio of 7:3, and the performance of different machine learning models were compared by 10-fold cross-validation, and the model algorithm with the best performance was selected from 15 models to construct and validate the depression prediction model for home-quarantined subjects. The validity of different models was compared based on accuracy, precision, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC), and the best model suitable for the data framework of this study was identified. RESULTS: The prevalence of depression among home-quarantined individuals during the epidemic was 31.66% (202/638), and the constructed Adaboost depression prediction model had an ACC of 0.7917, an accuracy of 0.7180, and an AUC of 0.7803, which was better than the other 15 models on the combination of various performance measures. In the validation sets, the AUC was greater than 0.83. CONCLUSIONS: The Adaboost machine learning algorithm developed in this study can be used to construct a depression prediction model for home-quarantined individuals that has better machine learning performance, as well as high effectiveness, robustness, and generalizability.

Lipidomics Profiling Reveals Serum Phospholipids Associated with Albuminuria in Early Type 2 Diabetic Kidney Disease.

Early screening and administration of DKD are beneficial for renal outcomes of type 2 diabetic patients. However, the current early diagnosis using the albuminuria/creatine ratio (ACR) contains limitations. This study aimed to compare serum lipidome variation between type 2 diabetes and early DKD patients with increased albuminuria through an untargeted lipidomics method to explore the potential lipid biomarkers for DKD identification. 92 type 2 diabetic patients were enrolled and divided into two groups: DM group (ACR < 3 mg/mmol, n = 49) and early DKD group (3 mg/mmol ≤ ACR < 30 mg/mmol, n = 43). Fasting serum was analyzed through an ultraperformance liquid mass spectrometry tandem chromatography system (LC-MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate and multivariate analysis were performed to filter differentially depressed lipids. Receiver operating characteristic (ROC) curves were used to estimate the diagnostic capability of potential lipid biomarkers. We found that serum phospholipids including phosphatidylserine (PS), sphingomyelin (SM), and phosphatidylcholine (PC) were significantly upregulated in the DKD group and were highly correlated with the ACR. In addition, a panel of two phospholipids including PS(27:0)-H and PS(30:2e)-H showed good performance to help clinical lipids in early DKD identification, which increased the area under the curve (AUC) from 0.568 to 0.954. The study exhibited the serum lipidome variation in early DKD patients, and the increased phospholipids might participate in the development of albuminuria. The panel of PS(27:0)-H and PS(30:2e)-H could be a potential biomarker for DKD diagnosis.

Impact of sarcosine on diabetic retinopathy: Findings based on weighted gene co-expression network analysis and machine learning techniques.

AIM: To quantify the association between serum sarcosine and diabetic retinopathy (DR) using weighted gene co-expression network analysis (WGCNA). METHODS: We measured serum metabolites in 69 pairs of type 2 diabetes (T2D) patients with and without DR matched by age, gender, body mass index（BMI and HbA1c, using a propensity score matching-based approach. To identify modules and metabolites linked to DR, pathway analysis was performed using WGCNA, the Kyoto Encyclopedia of Genes and Genomes and Small-Molecule Pathway Database. The association of sarcosine with DR was estimated by restricted cubic spline and conditional logistic regression models. Its joint effects with covariates on DR were also extensively examined. RESULTS: With per interquartile range elevation of sarcosine, the adjusted odds ratio (AOR) of DR significantly decreased by 67% (AOR: 0.33, 95% confidence interval [CI]: 0.19-0.58). Similar results were also found in the tertile analysis. Compared with those in the first tertile of sarcosine, the AOR significantly decreased by 54% (AOR: 0.46, 95% CI: 0.18-1.17) and 78% (AOR: 0.22, 95% CI: 0.08-0.59) for subjects in the second and third tertiles, respectively. Compared with subjects with lower sarcosine and lower HDL-C levels, those with higher sarcosine and lower HDL-C levels had the lowest odds of DR (OR: 0.13, 95% CI: 0.04, 0.43). CONCLUSIONS: Serum sarcosine was inversely related to DR, especially in T2D patients with insufficient HDL-C. This study provides insights on a possible novel target for DR precision prevention and control, as well as a better understanding of the DR mechanism.

Anemia is independently associated with mortality in people living with human immunodeficiency virus/acquired immune deficiency syndrome: A propensity score matching-based retrospective cohort study in China.

Although previous studies have suggested that hemoglobin is related to the health status of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) (PLWHA), the role of anemia in mortality remains unclear. This study aimed to comprehensively quantify the effect of anemia on the mortality risk of PLWHA. In this retrospective cohort study, we thoroughly estimated the effect of anemia on PLWHA mortality, using data collected from January 2005 to June 2022 in the Huzhou area, in 450 subjects extracted from the database of the China Disease Prevention and Control Information System and matched them using a propensity score matching approach to balance potential confounding bias. The potential exposure-response relationship between anemia, hemoglobin concentration, and the mortality of PLWHA was also carefully estimated. A series of subgroup analyses, including interaction analysis, was further conducted to validate the robustness of the effect of anemia on PLWHA death risk. Anemia was significantly associated with an elevated death risk in PLWHA, with an increase of 74% (adjusted hazard ratio [AHR]: 1.74; 95% confidence interval [CI]: 1.03-2.93; p = 0.038) in those with anemia after adjusting for potential confounders. PLWHA with moderate or severe anemia had a higher risk of death, with an 86% increase (AHR = 1.86; 95% CI: 1.01-3.42; p = 0.045). Meanwhile, the AHR tended to increase by 85% on average (AHR = 1.85, 95% CI: 1.37-2.50; p < 0.001) with a per standard deviation (SD) decrease in plasma hemoglobin. Consistent relationships between plasma hemoglobin and the risk of death were further observed in the results from multiple quantile regression models, restricted cubic spline regression models, and a series of subgroup analyses. Anemia is an independent risk factor for HIV/AIDS-related mortality. Our findings may provide new insights into the relevance of PLWHA administration to public health policy, which demonstrate that this low-cost and routinely measured marker (hemoglobin) can be a marker of poor prognosis even before the start of HAART.

Serum total folate, 5-methyltetrahydrofolate and vitamin B12 concentrations on incident risk of lung cancer.

Tobacco smoking is a major known risk factor for lung cancer. While micronutrients, especially those involved in maintaining DNA integrity and regulating gene expression, may be protective, research on this association is limited. This report aimed to investigate associations of total folate, 5-methyltetrahydrofolate (5-mTHF) and vitamin B12 with incident risk of lung cancer, and whether the associations vary by smoking status. A nested case-control study with 490 incident lung cancer cases and 490 controls matched by age (±1 year), sex, residence, and center, drawn from a community-based prospective study in China, was conducted from 2016 to 2019. 5-mTHF accounted for the majority of total folate. Only 4.4% had detectable unmetabolized folic acid. Lung cancer cases had lower levels of 5-mTHF compared to controls. There was an inverse, nonlinear association between 5-mTHF and lung cancer, which persisted after adjustment for covariables (P for trend = .001). Compared to the lowest 5-mTHF quartile, those in higher quartiles had lower risks of lung cancer: second quartile OR = 0.65; 95% CI: 0.45-0.93; third quartile OR = 0.50; 95% CI: 0.34-0.74; fourth quartile OR = 0.56; 95% CI: 0.38-0.83. This inverse association was more pronounced among ever smokers; consistently, the highest risk of lung cancer (OR = 3.21, 95% CI: 1.97-5.24) was observed among ever smokers with low 5-mTHF levels compared to participants who never smoked and had higher 5-mTHF levels. Vitamin B12 was not associated with lung cancer risk. In this sample of Chinese adults without confounding by unmetabolized folic acid, higher levels of 5-mTHF were associated with lower risk of incident lung cancer.

Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China.

Background and purpose: Acylcarnitines (ACars) are important for insulin resistance and type 2 diabetes (T2D). However, their roles in diabetic retinopathy (DR) remain controversial. In this study, we aimed to investigate the association of ACars with DR and their values in DR detection. Methods: This was a two-center case-control study based on the propensity score matching approach between August 2017 to June 2018 in Eastern China. Multivariable logistic regression models were applied to estimate the association of plasma ACars with DR. Differential ACars were screened by models of least absolute shrinkage and selection operator, elastic net, and weighted quantile sum regression, and their roles in DR identification were further evaluated by the area under the receiver operating curve (AUC). Results: Eight of twenty plasma ACars (8:0, 12:0, 12:1, 14:1, 16:2, 18:0, 18:2 and 18:3) were associated with DR, while only ACar 8:0 was selected by three variable selection methods. As compared to those with the 1st tertile of ACar 8:0, the adjusted odds ratio (OR) and 95% confidence interval (CI) of DR were 0.22 (0.08, 0.59) and 0.12 (0.04, 0.36) for subjects in the 2nd and 3rd tertiles, respectively (P for trend < 0.001). Consistent associations were also observed in both restricted cubic spline regression models and subgroup analyses. AUC (95% CI) were 0.74 (0.66, 0.82) for ACar 8:0 alone and 0.77 (0.70, 0.85) for ACar 8:0 combined with covariates. Conclusions: Our findings suggest higher ACar 8:0 is significantly associated with a decreased risk of DR, which provides a unique window for early identification of DR.

Elementary school comprehensive intervention and myopia development: the Wenzhou Epidemiology of Refraction Error Study.

AIM: To investigate the effects of school-based comprehensive intervention on myopia development in elementary school children. METHODS: As a part of the Wenzhou Epidemiology of Refraction Error Study, there were 1524 participating elementary students (730 girls, 47.9%) in grades 1 to 3 from three campuses of one school, aged 7.3±0.9y, who were examined twice every year for a 2.5y follow up period. Comprehensive intervention and other reminders were given at school every semester for the intervention group. The control group did not receive comprehensive intervention and did not have reminders of it. RESULTS: There were 651 students in the intervention group [mean age 7.3±0.9y; 294 (45.2%) girls] and 737 students in the control group [mean age 7.2±0.9y; 346 (46.9%) girls]. Overall mean myopia progression during the 2.5y follow-up was -0.49±1.04 diopters (D) in the intervention group and -0.65±1.08 D in the control group (P=0.004). The majority that not get myopia at baseline spherical equivalent (SE≤-1.0 D). Their mean myopia progression during the 2.5y follow-up was -0.37±0.89 D in the intervention group and -0.51±0.93 D in the control group (27.5% reduction, P=0.009); Overall, mean axial length elongation was less in the intervention group (0.56±0.32 mm) than in the control group (0.61±0.38 mm, 10.5% reduction, P=0.009). The percentage of close reading distance (<30 cm) in the intervention group was less than in the control group (73.4% vs 76.2%, P<0.001), the percentage of everyday perform eye exercises in the intervention group was more than in the control group (27.8% vs 20.7%, P<0.001) 30mo later. CONCLUSION: The comprehensive intervention program at elementary school has a significant alleviating effect on myopia progression for children during the 2.5y follow-up, especially for those non-myopia at baseline.

Interpretable machine learning-derived nomogram model for early detection of diabetic retinopathy in type 2 diabetes mellitus: a widely targeted metabolomics study.

OBJECTIVE: Early identification of diabetic retinopathy (DR) is key to prioritizing therapy and preventing permanent blindness. This study aims to propose a machine learning model for DR early diagnosis using metabolomics and clinical indicators. METHODS: From 2017 to 2018, 950 participants were enrolled from two affiliated hospitals of Wenzhou Medical University and Anhui Medical University. A total of 69 matched blocks including healthy volunteers, type 2 diabetes, and DR patients were obtained from a propensity score matching-based metabolomics study. UPLC-ESI-MS/MS system was utilized for serum metabolic fingerprint data. CART decision trees (DT) were used to identify the potential biomarkers. Finally, the nomogram model was developed using the multivariable conditional logistic regression models. The calibration curve, Hosmer-Lemeshow test, receiver operating characteristic curve, and decision curve analysis were applied to evaluate the performance of this predictive model. RESULTS: The mean age of enrolled subjects was 56.7 years with a standard deviation of 9.2, and 61.4% were males. Based on the DT model, 2-pyrrolidone completely separated healthy controls from diabetic patients, and thiamine triphosphate (ThTP) might be a principal metabolite for DR detection. The developed nomogram model (including diabetes duration, systolic blood pressure and ThTP) shows an excellent quality of classification, with AUCs (95% CI) of 0.99 (0.97-1.00) and 0.99 (0.95-1.00) in training and testing sets, respectively. Furthermore, the predictive model also has a reasonable degree of calibration. CONCLUSIONS: The nomogram presents an accurate and favorable prediction for DR detection. Further research with larger study populations is needed to confirm our findings.

His-bundle pacing vs biventricular pacing following atrioventricular nodal ablation in patients with atrial fibrillation and reduced ejection fraction: A multicenter, randomized, crossover study-The ALTERNATIVE-AF trial.

BACKGROUND: Atrioventricular nodal ablation (AVNA) combined with biventricular pacing (BVP) improves outcomes in patients with persistent atrial fibrillation (AF), adequate rate control, and reduced left ventricular ejection fraction (LVEF). His-bundle pacing (HBP) delivers physiological ventricular activation and is a promising alternative to BVP. OBJECTIVE: The purpose of this trial was to compare HBP with BVP following AVNA. METHODS: In this multicenter, prospective, randomized crossover trial, we recruited patients with persistent AF and reduced LVEF (≤40%). All patients underwent AVNA and received both HBP and BVP. Patients were randomized to either HBP or BVP for 9 months (phase 1), then were switched to the alternative pacing modality for the next 9 months (phase 2). The primary endpoint was change in LVEF. RESULTS: Fifty patients (age 64.3 ± 10.3 years; ventricular rate 93.1 ± 19.9 bpm; 72% male) were enrolled. Thirty-eight patients completed the 2 phases and were included in the crossover analysis. A significant improvement in LVEF was observed with HBP compared to BVP (phase 1: ΔLVEFHBP 21.3% and ΔLVEFBVP 16.7%; phase 2: ΔLVEFHBP 3.5% and ΔLVEFBVP -2.4%; Pgeneralizedadditivemodel = 0.015). Significant improvements in left ventricular end-diastolic diameter, New York Heart Association functional class, and B-type natriuretic peptide level were observed with both pacing modalities compared with baseline, whereas no significant differences were observed between HBP and BVP. CONCLUSION: HBP delivers a modest but significant improvement in LVEF in patients with persistent AF, impaired ventricular function, and narrow QRS duration post-AVNA compared with BVP. Larger long-term trials are required to confirm the additional improvements in function with HBP.

The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma.

BACKGROUND: As a DNA surveillance mechanism, cell cycle checkpoint has recently been discovered to be closely associated with lung adenocarcinoma (LUAD) prognosis. It is also an essential link in the process of DNA damage repair (DDR) that confers resistance to radiotherapy. Whether genes that have both functions play a more crucial role in LUAD prognosis remains unclear. METHODS: In this study, DDR-related genes with cell cycle checkpoint function (DCGs) were selected to investigate their effects on the prognosis of LUAD. The TCGA-LUAD cohort and two GEO external validation cohorts (GSE31210 and GSE42171) were performed to construct a prognosis model based on the least absolute shrinkage and selection operator (LASSO) regression. Patients were divided into high-risk and low-risk groups based on the model. Subsequently, the multivariate COX regression was used to construct a prognostic nomogram. The ssGSEA, CIBERSORT algorithm, TIMER tool, CMap database, and IC50 of chemotherapeutic agents were used to analyze immune activity and responsiveness to chemoradiotherapy. RESULTS: 4 DCGs were selected as prognostic signatures, and patients in the high-risk group had a lower overall survival (OS). The lower infiltration levels of immune cells and the higher expression levels of immune checkpoints appeared in the high-risk group. The damage repair pathways were upregulated, and chemotherapeutic agent sensitivity was poor in the high-risk group. CONCLUSIONS: The 4-DCGs signature prognosis model we constructed could predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.

Inverse Association between Plasma Phylloquinone and Risk of Ischemic Stroke in Chinese Adults with Hypertension and High BMI: A Nested Case-Control Study.

BACKGROUND: Evidence on the association between phylloquinone status and cardiovascular diseases is scarce and conflicting. These inconsistencies may be due to differences in individual characteristics of the study populations, which may modify the association. OBJECTIVE: This study aimed to evaluate the association between plasma phylloquinone and the risk of first total stroke and its subtypes, and to examine potential effect modifications by BMI in patients with hypertension. METHODS: We performed a nested case-control study including 604 first stroke cases and 604 matched controls. The mean age was 62.2 y (range, 45 to 75). Lower BMI was defined as <25 kg/m2  and higher BMI was defined as ≥25 kg/m2. The risks of the first stroke were estimated by ORs and 95% CIs using conditional logistic regression. The primary outcome was total stroke or ischemic stroke. RESULTS: The relation between log-transformed phylloquinone concentration and stroke or ischemic stroke was modified by BMI. Higher phylloquinone concentrations were associated with lower stroke risk in those with a higher BMI. When plasma phylloquinone was assessed as tertiles, the adjusted ORs of first stroke and ischemic stroke for participants with a high BMI in tertile 2-3 were 0.70 (95% CI: 0.46, 1.08) and 0.57 (95% CI: 0.35, 0.92) compared with those in tertile 1, respectively. However, there was no significant association between plasma phylloquinone and risk of first total stroke or ischemic stroke for those with a lower BMI. Patients with a higher BMI and lower phylloquinone concentrations had the highest risk of ischemic stroke and showed a statistically significant difference compared with the reference group with a lower BMI and higher phylloquinone (OR = 1.80, 95% CI: 1.06, 3.10; P-interaction: 0.017). CONCLUSIONS: In Chinese patients with hypertension, there was an inverse association between baseline plasma phylloquinone and risk of first ischemic stroke among those with a higher BMI. This trial was registered at clinicaltrials.gov as NCT00794885.

Development and validation of a novel nomogram for predicting the occurrence of myopia in schoolchildren: A prospective cohort study.

PURPOSE: Myopia is a major public health issue and occurs at young ages. Apart from its high prevalence, myopia results in high costs and irreversible blinding diseases. Accurate prediction of the risk of myopia onset is crucial for its precise prevention. We aimed to develop and validate an effective nomogram for predicting myopia onset in schoolchildren. DESIGN: School-based prospective cohort study. METHODS: A total of 1073 schoolchildren were enrolled from November 2014 to May 2019 in China, and were divided into the training and validation cohorts. Myopia was defined as a spherical equivalent refraction (SER) ≤-0.5 diopters. Predictors of myopia were determined through the least absolute shrinkage and selection operator regression and multivariable Cox proportional hazard model based on the training cohort. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic (ROC) curves, calibration plot, decision curve analysis, and Kaplan-Meier curves. RESULTS: Independent predictors at baseline including gender, SER, axial length, corneal refractive power, and positive relative accommodation were included in the nomogram prediction model. This nomogram demonstrated excellent calibration, clinical net benefit, and discrimination, with all the area under the ROC curves (AUCs) between 0.74 and 0.86 in the training and validation cohorts. The Kaplan-Meier curves showed that 3 distinct risk groups stratified through X-tile analysis were well discriminated and robust among subgroups. The Harrell's C-index and net reclassification improvement demonstrated that the nomogram substantially improved compared with previous models. An online myopia risk calculator was generated for better individual prediction. CONCLUTIONS: The nomogram provides accurate and individual prediction of myopia onset in schoolchildren. External validation is needed to verify the generalizability of this nomogram.

Joint Association of Low Vitamin K1 and D Status With First Stroke in General Hypertensive Adults: Results From the China Stroke Primary Prevention Trial (CSPPT).

Background: Vitamin K plays a role in preventing vascular calcification and may have a synergetic influence with vitamin D on cardiovascular health. However, whether this relationship applies to stroke, especially in a high-risk population of hypertensive individuals, remains unclear. The present study aims to study the joint association of low vitamin K1 and D status with first stroke in general hypertensive adults. Methods: This study used a nested, case-control design with data from the China Stroke Primary Prevention Trial. The analysis included 604 first total stroke patients and 604 matched controls from a Chinese population with hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression. Results: There was a non-linear negative association between plasma vitamin K1 and the risk of first total stroke or ischemic stroke in the enalapril-only group. Compared to participants in vitamin K1 quartile 1, a significantly lower risk of total stroke (OR = 0.58, 95% CI: 0.36, 0.91, P = 0.020) or ischemic stroke (OR = 0.34, 95% CI: 0.17, 0.63, P < 0.001) was found in participants in vitamin K1 quartile 2-4 in the enalapril-only group. When further divided into four subgroups by 25(OH)D and vitamin K1, a significantly higher risk of total stroke or ischemic stroke was observed in participants with both low vitamin K1 and 25(OH)D compared to those with both high vitamin K1 and 25(OH)D in the enalapril-only group. No increased risk was observed in the groups low in one vitamin only. Conclusion: Low concentrations of both vitamin K1 and 25(OH)D were associated with increased risk of stroke.

High-Coverage Serum Metabolomics Reveals Metabolic Pathway Dysregulation in Diabetic Retinopathy: A Propensity Score-Matched Study.

Background: Diabetic retinopathy (DR) is a major diabetes-related disease linked to metabolism. However, the cognition of metabolic pathway alterations in DR remains scarce. We aimed to corroborate alterations of metabolic pathways identified in prior studies and investigate novel metabolic dysregulations that may lead to new prevention and treatment strategies for DR. Methods: In this case-control study, we tested 613 serum metabolites in 69 pairs of type 2 diabetic patients (T2DM) with DR and propensity score-matched T2DM without DR via ultra-performance liquid chromatography-tandem mass spectrometry system. Metabolic pathway dysregulation in DR was thoroughly investigated by metabolic pathway analysis, chemical similarity enrichment analysis (ChemRICH), and integrated pathway analysis. The associations of ChemRICH-screened key metabolites with DR were further estimated with restricted cubic spline analyses. Results: A total of 89 differentially expressed metabolites were identified by paired univariate analysis and partial least squares discriminant analysis. We corroborated biosynthesis of unsaturated fatty acids, glycine, serine and threonine metabolism, glutamate and cysteine-related pathways, and nucleotide-related pathways were significantly perturbed in DR, which were identified in prior studies. We also found some novel metabolic alterations associated with DR, including the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives in DR. Conclusions: The results suggest that the metabolism disorder in DR can be better understood through integrating multiple biological knowledge databases. The progression of DR is associated with the disturbance of thiamine metabolism and tryptophan metabolism, decreased trehalose, and increased choline and indole derivatives.

Observation seasonal variation of intraocular pressure in young healthy volunteers.

AIM: To investigate fluctuation of intraocular pressure (IOP) and seasonal variation of 24-hour IOP during one year in healthy participants. METHODS: Totally 13 young healthy volunteers participated in this study. IOP was measured with Canon TX-20 at about 8:00-9:00 a.m. from Monday to Friday every week for a whole year. They also underwent 24-hour IOP examination every three months. Blood pressure, heart rate, temperature, humidity, atmosphere pressure, sunshine duration and other environment parameters were recorded. RESULTS: The yearly fluctuation curve showed IOP in the summer months were lower than other seasons. In the multivariable generalized estimating equation analysis, IOP had a negative correlation with both temperature and sunshine duration (P<0.05). There also was a seasonal effect on 24-hour IOP. However, all intraclass correlation coefficients values of minimum, maximum and average of the 24-hour IOP and each individual IOP were less than 0.30. CONCLUSION: IOP is trend to be higher in cold days than warm days. IOP have negative association with both environmental temperature and duration of sunshine. On a season-to-season basis, 24-hour IOP is not highly reproducible in healthy volunteers.

A novel raiometric fluorescence probe based on silicon quantum dots and copper nanoclusters for visual assay of l-cysteine in milks.

l-cysteine (l-Cys) plays an important role in many physiological processes. The previously reported methodologies for l-Cys detection have many drawbacks, and thus the development of specific/sensitive approaches is crucial for its direct/quick assay in food matrices. Herein, silicon quantum dots (SiQDs) and glutathione-stabilized copper nanoclusters (CuNCs) were successfully synthesized and integrated as a ratiometric fluorescent probe for assay l-Cys assay in milks. The fluorescence of SiQDs was quenched by CuNCs through fluorescence resonance energy-transfer process. Upon addition of l-Cys, the 440-nm fluorescence of SiQDs changed insignificantly, while the 650-nm fluorescence of CuNCs decreased significantly. Ratiometric fluorescence signal was linear in the l-Cys concentration range of 0.25 µM to 2.5 mM with a detection limit of 75 nM and visual color changes from red to blue. The probe can realize rapid and portable detection without the participation of intermediate ions, and has good selectivity and accuracy for l-cysteine in milk samples.