Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Targeted proteomics-determined multi-biomarker profiles developed classifier for prognosis and immunotherapy responses of advanced cervical cancer.

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.

Trends in cardiovascular risk factor prevalence, treatment, and control among US adolescents aged 12 to 19 years, 2001 to March 2020.

BACKGROUND: Early-life cardiovascular risk factors (CVRFs) are known to be associated with target organ damage during adolescence and premature cardiovascular morbidity and mortality during adulthood. However, contemporary data describing whether the prevalence of CVRFs and treatment and control rates have changed are limited. This study aimed to examine the temporal trends in the prevalence, treatment, and control of CVRFs among US adolescents over the past 2 decades. METHODS: This is a serial cross-sectional study using data from nine National Health and Nutrition Examination Survey cycles (January 2001-March 2020). US adolescents (aged 12 to 19 years) with information regarding CVRFs (including hypertension, elevated blood pressure [BP], diabetes, prediabetes, hyperlipidemia, obesity, overweight, cigarette use, inactive physical activity, and poor diet quality) were included. Age-adjusted trends in CVRF prevalence, treatment, and control were examined. Joinpoint regression analysis was performed to estimate changes in the prevalence, treatment, and control over time. The variation by sociodemographic characteristics were also described. RESULTS: A total of 15,155 US adolescents aged 12 to 19 years (representing ≈ 32.4 million people) were included. From 2001 to March 2020, there was an increase in the prevalence of prediabetes (from 12.5% [95% confidence interval (CI), 10.2%-14.9%] to 37.6% [95% CI, 29.1%-46.2%]) and overweight/obesity (from 21.1% [95% CI, 19.3%-22.8%] to 24.8% [95% CI, 21.4%-28.2%]; from 16.0% [95% CI, 14.1%-17.9%] to 20.3% [95% CI, 17.9%-22.7%]; respectively), no improvement in the prevalence of elevated BP (from 10.4% [95% CI, 8.9%-11.8%] to 11.0% [95% CI, 8.7%-13.4%]), diabetes (from 0.7% [95% CI, 0.2%-1.2%] to 1.2% [95% CI, 0.3%-2.2%]), and poor diet quality (from 76.1% [95% CI, 74.0%-78.2%] to 71.7% [95% CI, 68.5%-74.9%]), and a decrease in the prevalence of hypertension (from 8.1% [95% CI, 6.9%-9.4%] to 5.5% [95% CI, 3.7%-7.3%]), hyperlipidemia (from 34.2% [95% CI, 30.9%-37.5%] to 22.8% [95% CI, 18.7%-26.8%]), cigarette use (from 18.0% [95% CI, 15.7%-20.3%] to 3.5% [95% CI, 2.0%-5.0%]), and inactive physical activity (from 83.0% [95% CI, 80.7%-85.3%] to 9.5% [95% CI, 4.2%-14.8%]). Sex and race/ethnicity affected the evolution of CVRF prevalence differently. Whilst treatment rates for hypertension and diabetes did not improve significantly (from 9.6% [95% CI, 3.5%-15.8%] to 6.0% [95% CI, 1.4%-10.6%]; from 51.0% [95% CI, 23.3%-78.7%] to 26.5% [95% CI, 0.0%-54.7%]; respectively), BP control was relatively stable (from 75.7% [95% CI, 56.8%-94.7%] to 73.5% [95% CI, 40.3%-100.0%]), while glycemic control improved to a certain extent, although it remained suboptimal (from 11.8% [95% CI, 0.0%-31.5%] to 62.7% [95% CI, 62.7%-62.7%]). CONCLUSIONS: From 2001 to March 2020, although prediabetes and overweight/obesity increased, hypertension, hyperlipidemia, cigarette use, and inactive physical activity decreased among US adolescents aged 12 to 19 years, whereas elevated BP, diabetes, and poor diet quality remained unchanged. There were disparities in CVRF prevalence and trends across sociodemographic subpopulations. While treatment and control rates for hypertension and diabetes plateaued, BP control were stable, and improved glycemic control was observed.

Predictive Value of Amplitude-Integrated Electroencephalogram Combined with General Movements for Neurodevelopmental Outcomes in Neonates with Severe Hyperbilirubinemia.

Objective: To investigate the predictive value of amplitude-integrated electroencephalogram (aEEG) combined with general movements (GMs) for neurodevelopmental outcomes in neonates with severe hyperbilirubinemia. Methods: A total of 115 infants with severe hyperbilirubinemia admitted to our hospital from December 2021 to February 2024 were enrolled. All the subjects were tested using aEEG, GMs, cranial magnetic resonance imaging (MRI), or auditory brainstem response (ABR), and followed up for 12 months to evaluate the neurodevelopmental outcomes. Results: Among the 100 children who received follow-up, 19 had adverse neurodevelopmental outcomes. They had significantly higher levels of total serum bilirubin (P < .05) than those with positive neurodevelopmental outcomes. The examination results of abnormalities in aEEG, GMs, ABR, aEEG + GMs, aEEG + ABR, and MRI + ABR are all correlated with adverse neurodevelopmental outcomes (P < .05). Logistic regression analysis indicated that abnormal aEEG, GMs, and ABR were predictors of adverse neurodevelopmental outcomes. The aEEG + GMs method significantly outperformed the individual use of aEEG or GMs in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Conclusion: The aEEG + GMs technique can predict the neurodevelopmental outcomes of neonates with severe hyperbilirubinemia and outperforms the individual use of aEEG or GMs in terms of sensitivity, specificity, positive predictive value, and negative predictive value. As a result, the combined technique merits broader clinical use.

Characterization of Four Complete Mitogenomes of Monolepta Species and Their Related Phylogenetic Implications.

Monolepta is one of the diverse genera in the subfamily Galerucinae, including 708 species and 6 sub-species worldwide. To explore the information on the mitogenome characteristics and phylogeny of the section "Monoleptites", especially the genus Monolepta, we obtained the newly completed mitochondrial genomes (mitogenomes) of four Monolepta species using high-throughput sequencing technology. The lengths of these four new mitochondrial genomes are 16,672 bp, 16,965 bp, 16,012 bp, and 15,866 bp in size, respectively. All four mitochondrial genomes include 22 transfer RNA genes (tRNAs), 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and one control region, which is consistent with other Coleoptera. The results of the nonsynonymous with synonymous substitution rates showed that ND6 had the highest evolution rate, while COI displayed the lowest evolution rate. The substitution saturation of three datasets (13 PCGs_codon1, 13 PCGs_codon2, 13 PCGs_codon3) showed that there was no saturation across all datasets. Phylogenetic analyses based on three datasets (ND1, 15 genes of mitogenomes, and 13 PCGs_AA) were carried out using maximum likelihood (ML) and Bayesian inference (BI) methods. The results showed that mitogenomes had a greater capacity to resolve the main clades than the ND1 gene at the suprageneric and species levels. The section "Monoleptites" was proven to be a monophyletic group, while Monolepta was a non-monophyletic group. Based on ND1 data, the newly sequenced species whose antennal segment 2 was shorter than 3 were split into several clades, while, based on the mitogenomic dataset, the four newly sequenced species had close relationships with Paleosepharia. The species whose antennal segment 2 was as long as 3 were split into two clades, which indicated that the characteristic of "antennal segment 2 as long as 3" of the true "Monolepta" evolved multiple times in several subgroups. Therefore, to explore the relationships among the true Monolepta, the most important thing is to perform a thorough revision of Monolepta and related genera in the future.

Comparison of arterial stiffness indices measured by pulse wave velocity and pulse wave analysis for predicting cardiovascular and all-cause mortality in a Chinese population.

Arterial stiffness measured by pulse wave velocity and pulse wave analysis has been widely studied in different populations in terms of its correlation with cardiovascular events and all-cause mortality. It remains unknown which arterial stiffness index is better for risk stratification in the general population. We included 4129 participants from Gaoyou County, Jiangsu Province, China, with a median follow-up of 11 years. The primary endpoint was cardiovascular mortality, and the secondary endpoint was all-cause mortality. Harrell's C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) based on the Cox proportional hazards regression model were evaluated to assess predictive discrimination and accuracy. The associations between the 4 indices and cardiovascular mortality remained significant after adjusting for the Framingham Risk Score (FRS) and/or associated risk factors. Considering reclassification based on the newly integrated models (FRS model combined with the 4 indices), NRI for cardiovascular mortality showed that haPWV and baPWV had more significant improvement in reclassification compared with C1 and C2 [NRI with 95% CI: haPWV 0.410 (0.293, 0.523); baPWV 0.447 (0.330, 0.553); C1 0.312 (0.182, 0.454); C2 0.328 (0.159, 0.463); all P < 0.05]. This study showed that pulse wave velocity (haPWV and baPWV) provides better discrimination of long-term risk than arterial elasticity indices (C1 and C2) in the general population.

Low lean mass with obesity in older adults with hypertension: prevalence and association with mortality rate.

BACKGROUND: The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. METHODS: We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999-2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. RESULTS: In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14-2.49, P = 0.008; HR 1.48, 95% CI 1.04-2.10, P = 0.028; HR 1.30, 95% CI 1.02-1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Diffusion Depth and Efficacy of Different Infiltration Times for Rose Bengal/Green Light Corneal Cross-linking in Rabbit Eyes.

PURPOSE: To explore the diffusion depth and green light corneal cross-linking efficacy of different rose bengal (Rb) infiltration times in rabbit eyes. METHODS: Twenty-eight fresh rabbit eyes were deepithelialized and infiltrated in 0.1% Rb solution for 2 to 30 minutes. Corneal frozen sections were cut and Rb diffusion depth was observed under the confocal microscope. A further 36 rabbits were randomly divided into eight groups according to the type of treatment (control, Rb infiltration only without irradiation, rose bengal/green light [RGX] for different infiltration times, or riboflavin/ultraviolet radiation [UVX]). The corneas' resistance to keratolysis and biomechanical properties were measured after treatment. RESULTS: After 2, 10, 20, and 30 minutes of infiltration, Rb penetration depths in the corneal stroma were 100, 150, 200, and 270 µm, respectively. The times for complete digestion of the RGX 10 minutes (14.0 ± 1.4 hours), RGX 20 minutes (18.8 ± 1.1 hours), and UVX (51.2 ± 7.2 hours) groups were statistically greater than that of the control group (7.2 ± 1.1 hours). At 10% extension, the Young's modulus of the RGX 20 minutes (36.59 ± 4.90 MPa) and UVX (40.89 ± 2.57 MPa) groups was statistically greater than that of the control group (21.76 ± 5.69 MPa). CONCLUSIONS: The diffusion depth of Rb in corneal stroma increased by prolonging the infiltration time. The longer the infiltration time, the better the RGX effect. RGX for 20 minutes showed the best cross-linking efficacy among all RGX groups, albeit not as good as UVX. [J Refract Surg. 2023;39(9):620-626.].

Extracellular Vesicles and Pathological Cardiac Hypertrophy.

Pathological cardiac hypertrophy is a well-recognized risk factor for cardiovascular diseases (CVDs). Although lots of efforts have been made to illustrate the underlying molecular mechanisms, many issues remain undiscovered. Recently, intercellular communication by delivering small molecules between different cell types in the progression of cardiac hypertrophy has been reported, including bioactive nucleic acids or proteins. These extracellular vesicles (EVs) may act in an autocrine or paracrine manner between cardiomyocytes and noncardiomyocytes to provoke or inhibit cardiac remodeling and hypertrophy. Besides, EVs can be used as novel diagnostic or prognostic biomarkers in cardiac hypertrophy and also may serve as potential therapeutic targets due to its biocompatible nature and low immunogenicity. In this chapter, we will first summarize the current knowledge about EVs from different cells in pathological cardiac hypertrophy. Then, we will focus on the value of EVs as therapeutic agents and biomarkers for pathological myocardial hypertrophy.

Negative association between triglyceride glucose index and BMI-adjusted skeletal muscle mass index in hypertensive adults.

BACKGROUND: The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. METHODS: We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. RESULTS: A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted ß of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was - 5.27 (- 9.79 to - 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend < 0.05). CONCLUSION: This linear and negative correlation between TyG index and SMI in hypertensive patients suggests that insulin resistance adversely affects muscle mass.

Creatinine-based European Kidney Function Consortium equation is superior to the Chronic Kidney Disease Epidemiology Collaboration equation for mortality risk stratification in general non-Black population.

AIMS: A recent study demonstrated that the new modified estimated glomerular filtration rate (eGFR) equation proposed by the European Kidney Function Consortium (EKFC) was more accurate and precise than the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This study aimed to compare the prognostic values of these two creatinine-based equations with regard to all-cause and cardiovascular mortality in general non-Black population. METHODS AND RESULTS: A population-based cohort study was conducted using data from the National Health and Nutrition Examination Survey database from 1999 to 2018, and 38 983 non-Black individuals aged 20 years or older without a history of dialysis were enrolled. Among 38 983 participants, 6103 deaths occurred after a median follow-up duration of 112 months, of which 1558 deaths were due to cardiovascular causes. There were U-shaped relations between the eGFR values and the risk of all-cause and cardiovascular mortality. The areas under the curves for the EKFC were significantly higher than those for the CKD-EPI equation for all-cause and cardiovascular mortality. The integrated discrimination improvement for the EKFC equation compared with the CKD-EPI equation was 2.40% and 1.26% for 10-year all-cause and cardiovascular mortality; the net reclassification improvement for the EKFC equation compared with the CKD-EPI equation was 8.67% and 11.13% for 10-year all-cause mortality and cardiovascular mortality. CONCLUSION: Creatinine-based EKFC equation outperformed the CKD-EPI equation for the prediction of long-term all-cause and cardiovascular mortality in the general non-Black population.

This study compared the prognostic values of two creatinine-based equations [European Kidney Function Consortium (EKFC) and Chronic Kidney Disease Epidemiology Collaboration CKD-EPI)] with regard to all-cause and cardiovascular mortality in general non-Black population. This study confirmed U-shaped relations between estimated glomerular filtration rate values calculated with the EKFC and the CKD-EPI equation and the risk of all-cause and cardiovascular mortality.The EKFC equation outperformed the CKD-EPI equation for the prediction of long-term all-cause and cardiovascular mortality in general non-Black population.

Construction of a web-based dynamic nomogram for predicting the prognosis in acute heart failure.

AIMS: The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all-cause mortality in AHF patients. METHODS AND RESULTS: Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all-cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan-Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93-0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36-6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17-0.82; P = 0.014), N-terminal pro-B-type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01-1.03; P < 0.001), and rest scar burden (HR 1.03, 95% CI 1.01-1.06; P = 0.008) were independent risk factors for patients with AHF. The cross-validated AUCs (95% CI) of nomogram constructed by diastolic blood pressure, valvular heart disease, cardiac resynchronization therapy, N-terminal pro-B-type natriuretic peptide, and rest scar burden were 0.88 (0.73-1.00), 0.83 (0.70-0.97), and 0.79 (0.62-0.95) at 1, 3, and 5 years, respectively. Continuous net reclassification improvement and integrated discrimination improvement were also observed, and the decision curve analysis identified the greater net benefit of the nomogram across a wide range of threshold probabilities (0-100% at 1 and 3 years; 0-61% and 62-100% at 5 years) compared with dismissing the included factors or using either factor alone. CONCLUSIONS: A predictive nomogram for the risk of all-cause mortality in patients with AHF was developed and validated in this study. The nomogram incorporated the rest scar burden by MPI is highly predictive, and may help to better stratify clinical risk and guide treatment decisions in patients with AHF.

Induced regulatory T cells modified by knocking down T-bet in combination with ectopic expression of inhibitory cytokines effectively protect graft-versus-host disease.

Induced regulatory T (iTreg) cells play a vital role in immune tolerance and in controlling chronic inflammation. Generated in the periphery, iTreg cells are suitable for responding to alloantigens and preventing transplant rejection. Nevertheless, their clinical application has been impeded by the plasticity and instability attributed to the loss of forkhead box protein 3 expression, raising concerns that iTreg may be converted to effector T cells and even exert a pathogenic effect. Herein, second-generation short hairpin RNAs loaded with 3 pairs of small interfering RNAs were utilized to target the T-box transcription factor TBX21. In addition, 2 immunosuppressive cytokines, namely, transforming growth factor beta and interleukin 10, were constitutively expressed. This novel engineering strategy allowed the generation of stably induced regulatory T (SI Treg) cells, which maintained the expression of forkhead box protein 3 even in an unfavorable environment and exerted potent immunosuppressive functions in vitro. Furthermore, SI Treg cells demonstrated an effector transcriptional profile. Finally, SI Treg cells showed a significant protective effect against graft-versus-host disease-related deaths in a xenotransplantation model. Collectively, these results signify that SI Treg cells hold great promise for future clinical application and offer a rational therapeutic approach for transplant rejection.

Nonlinear associations of serum cobalamin with risk of all-cause and cardiovascular mortality in hypertensive adults.

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 and 2011-2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05-1.53) and 1.40 (1.17-1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71-2.61) and 73% (HR = 1.73, 1.55-1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults. This study was a prospective cohort study that included serum cobalamin data from 9934 hypertensive adults from the NHANES from 1999-2006 and 20011-2014. Findings suggested that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.

Associations of Serum Carotenoids With Risk of All-Cause and Cardiovascular Mortality in Hypertensive Adults.

Background Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2006 were included. Outcome measures (all-cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow-up duration of 16.6 years, all-cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all-cause mortality, with multivariable-adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56-0.71) for α-carotene, 0.70 (95% CI, 0.61-0.80); for ß-carotene, 0.67 (95% CI, 0.58-0.76); for ß-cryptoxanthin, 0.74 (95% CI, 0.64-0.86) for lycopene; and 0.72 (95% CI, 0.63-0.83) for lutein/zeaxanthin. For cause-specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α-carotene (HR, 0.68 [95% CI, 0.55-0.86]), a 29% reduction for ß-cryptoxanthin (HR, 0.71 [95% CI, 0.56-0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59-0.94]), but not for ß-carotene and lutein/zeaxanthin. In addition, we found that serum α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all-cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 µg/dL, respectively. Serum α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 µg/dL, respectively. Conclusions Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all-cause and cardiovascular mortality in hypertensive adults.

Associations of thiocyanate, nitrate, and perchlorate exposure with dyslipidemia: a cross-sectional, population-based analysis.

The aim of this study was to assess the associations of urinary thiocyanate, nitrate, and perchlorate concentrations with dyslipidemia, individually and in combination, which has not previously been studied. Data from the 2001-2002 and 2005-2016 National Health and Nutrition Examination Surveys (NHANES) were analyzed in this cross-sectional study. The dependent variables were continuous serum lipid variables (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-HDL-C, and apolipoprotein B [Apo B]) and binary serum lipid variables, with the latter reflecting dyslipidemia (elevated TG, ≥ 150 mg/dL; elevated TC, ≥ 200 mg/dL; elevated LDL-C, ≥ 130 mg/dL; lowered HDL-C, < 40 mg/dL in men and < 5 0 mg/dL in women; elevated non-HDL-C, ≥ 160 mg/dL; and elevated Apo B, ≥ 130 mg/dL). Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were used to explore the associations of thiocyanate, nitrate, and perchlorate with the continuous and binary serum lipid variables. The linearity of the associations with the binary serum lipid variables was assessed using restricted cubic spline (RCS) regression. A total of 15,563 adults were included in the analysis. The multivariate linear and logistic regression analyses showed that thiocyanate was positively associated with multiple continuous (TG, TC, LDL-C, non-HDL-C, and Apo B, but not HDL-C) and binary (elevated TG, TC, LDL-C, and non-HDL-C) serum lipid variables, whereas perchlorate was negatively associated with elevated LDL-C. Multivariate RCS logistic regression revealed a linear dose-response relationship between thiocyanate and elevated TG, TC, LDL-C, non-HDL-C, and Apo B, but a nonlinear relationship with lowered HDL-C (inflection point = 1.622 mg/L). WQS regression showed that a mixture of thiocyanate, nitrate, and perchlorate was positively associated with all binary serum lipid variables except for Apo B. Our findings indicate that urinary thiocyanate, nitrate, and perchlorate concentrations, individually and in combination, were associated with dyslipidemia.

[Stable angina pectoris of coronary heart disease treated with different acupuncture and moxibustion therapies: a network Meta-analysis].

To compare the clinical efficacy among different acupuncture and moxibustion therapies on stable angina pectoris (SAP) of coronary heart disease by means of network Meta-analysis. The articles of randomized controlled trial (RCT) for SAP of coronary heart disease treated with acupuncture and moxibustion therapies were searched from PubMed, Web of Science, Cochrane Library, CNKI, Wanfang database and VIP database from May 1, 2002 to May 1, 2022. The quality of them was assessed with the risk of bias assessment tool of Cochrane 5.3, and the network Meta-analysis was undertaken with Stata 13.1 software. A total of 29 articles were included with the acupuncture and moxibustion therapies involved, e.g. acupuncture, acupoint application and moxibustion. In comparison with the simple routine western medication, the effective rate was better on SAP treated with the combined treatments, in which, acupoint application, moxibustion, acupuncture and intradermal needling were combined with routine western medication (P<0.05). Of those combined treatments, the combination of the acupoint application with routine western medication had high probability, suggesting the optimal regimen (area under the curve [SUCRA]=0.711, P<0.05). The effective rate of acupuncture combined with routine western medication for ECG improvement was better than that of routine western medication (P<0.05), and such combined treatment was high in probability, underlying its optimal treatment (SUCRA=0.800, P<0.05). Combined with routine western medication, acupuncture, acupoint application, moxibustion and intradermal needling all improve the clinical efficacy on SAP of coronary heart disease. But, with different outcomes considered, the optimal treatments may be different. It needs more multi-central and large-sample randomized controlled trials to validate these results.

Assessment of corneal biomechanics in anisometropia using Scheimpflug technology.

Purpose: To investigate the relationship between corneal biomechanical and ocular biometric parameters, and to explore biomechanical asymmetry between anisometropic eyes using the corneal visualization Scheimpflug technology device (Corvis ST). Methods: 180 anisometropic participants were included. Participants were divided into low (1.00≤△Spherical equivalent (SE) < 2.00D), moderate (2.00D≤△SE < 3.00D) and high (△SE ≥ 3.00D) anisometropic groups. Axial length (AL), keratometry, anterior chamber depth (ACD) and corneal biomechanical parameters were assessed using the OA-2000 biometer, Pentacam HR and Corvis ST, respectively. Results: The mean age of participants was 16.09 ± 5.64 years. Stress-Strain Index (SSI) was positively correlated with SE (r = 0.501, p < 0.001) and negatively correlated with AL (r = -0.436, p < 0.001). Some other Corvis ST parameters had weak correlation with SE or AL. Corneal biomechanical parameters except for time of first applanation (A1T), length of second applanation (A2L), deformation amplitude (DA), first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) were correlated with ametropic parameters (SE or AL) in multiple regression analyses. A1T, velocity of first applanation (A1V), time of second applanation (A2T), A2L, velocity of second applanation (A2V), corneal curvature radius at highest concavity (HCR), peak distance (PD), DA, deformation amplitude ratio max (2 mm) (DAR), SPA1, integrated radius (IR), and SSI showed significant differences between fellow eyes (p < 0.05). There was no significant difference in asymmetry of corneal biomechanics among the three groups (p > 0.05). Asymmetry of some biomechanical parameters had weak correlation with asymmetry of mean corneal curvatures and ACD. However, asymmetry of corneal biomechanical parameters was not correlated with asymmetry of SE or AL (p > 0.05). Conclusion: More myopic eyes had weaker biomechanical properties than the contralateral eye in anisometropia. However, a certain linear relationship between anisometropia and biomechanical asymmetry was not found.

Intra-articular injection PLGA blends sustained-release microspheres loaded with meloxicam: preparation, optimization, evaluation in vitro and in vivo.

Meloxicam (MLX) is a commonly used drug in the clinical treatment of osteoarthritis, but it is associated with gastrointestinal adverse reactions. Therefore, in this study, we developed a sustained-release microsphere formulation of MLX for topical administration of knee joint. The MLX-loaded PLGA microspheres (MLX-MS) were prepared by emulsion solvent evaporation method with optimization of formulation using orthogonal experimental design. Physicochemical characterization results show MLX-MS were spherical with a smooth surface, the particle size was about 100 µm, drug loading was 30%, and encapsulation efficiency was 76.8%. In addition, the in vivo pharmacokinetics, tissue distribution, and pharmacodynamics were evaluated in rats by intra-articular administration of MLX. The microspheres showed a typical long-term sustained release pattern with a low initial burst release. In contrast to oral administration, local injection of MLX-MS produced a much higher value of elimination half-life time(T1/2) and peak time (Tmax) in plasma, while the intestinal drug distribution was significantly decreased. MLX-MS could also cause a greater reduction in the body level of IL-6 and TNF-α, which was positively correlated with R2=0.981. A good linear relationship (R2 = 0.9945) between the in vitro and in vivo drug release from MLX-MS could be observed, bivariate correlation analysis. All the findings demonstrated that local administration of MLX-MS can prolong the action time of MLX and reduce side effects, thus would be a promising preparation for the treatment of arthritis.