SR9009 attenuates inflammation-related NPMSC pyroptosis and IVDD through NR1D1/NLRP3/IL-1ß pathway.

Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.

ABA-importing transporter (AIT1) synergies enhances exogenous ABA minimize heavy metals accumulations in Arabidopsis.

Exogenous abscisic acid (ABA) presents a novel approach to mitigate heavy metal (HM) accumulation in plants, yet its efficacy against multiple HMs and potential enhancement methods remain underexplored. In this study, we demonstrated that the exogenous ABA application simultaneously decreased Zn, Cd and Ni accumulation by 22-25 %, 27-39 % and 60-62 %, respectively, in wild-type (WT) Arabidopsis. Conversely, ABA reduced Pb in shoots but increased its root concentration. ABA application also modulated the expression of HM uptake genes, inhibiting IRT1, NRAMP1, NRAMP4, and HMA3, and increasing ZIP1 and ZIP4 expressions. Further analysis revealed that overexpressing the ABA-importing transporter (AIT1) in plants intensified the reduction of Cd, Zn, and Ni, compared to WT. However, the inhibitory effect of exogenous ABA on Pb accumulation was mitigated in shoots with higher AIT1 expression. Furthermore, HMs-induced growth inhibition and the damage to photosynthesis were also alleviated with ABA treatment. Conclusively, AIT1's synergistic effect with ABA effectively reduces Cd, Zn and Ni accumulation, offering a synergistic approach to mitigate HM stress in plants.

Gender differences in the association between physical activity and cognitive subdomains among elders with type 2 diabetes and mild cognitive impairment: a cross-sectional study.

OBJECTIVES: The objective of this study was to evaluate the gender differences in the correlation between physical activity (PA) and cognitive subdomains in elderly individuals with type 2 diabetes (T2D) and mild cognitive impairment (MCI). DESIGN: Cross-sectional study. SETTING: The research was carried out in communities located in Fuzhou, Fujian Province and Beijing Municipality. PARTICIPANTS: Community-dwelling elders with T2D and MCI aged 60 years or older were eligible for this study. PRIMARY OUTCOME MEASURES AND ANALYSES: The weekly PA score was assessed using the International Physical Activity Questionnaire (IPAQ). The cognitive subdomains were evaluated through a battery of cognitive assessments, including the Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test Part B, Digit Symbol Substitution Test (DSST) and the Stroop Color-Word Test (SCWT). Multiple linear regression models were employed to examine the association between PA and cognitive subdomains in both male and female individuals. RESULTS: In older men, higher total IPAQ score was positively correlated with higher RAVLT (P=0.011) and SCWT (P=0.049). There was a significant interaction between the total PA score and gender in relation to RAVLT (P=0.008) and SCWT (P=0.027). Moreover, there was a positive correlation between moderate-vigorous PA level and RAVLT in older men (P=0.007). Additionally, a positive correlation was found between moderate-vigorous PA level and DSST in older women (P=0.038). CONCLUSION: In older individuals with T2D and MCI, the association between PA and cognitive subdomains differs between men and women. This discrepancy may impact the customisation of exercise recommendations.

Interactions between Beta-Amyloid and Pericytes in Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aß) that make up Aß plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aß through various receptors, and Aß acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aß1-40 and Aß1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aß from the brain interstitial fluid. The aggravated deposition of Aß further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aß is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aß, as well as current and further strategies for preventing or treating AD targeting pericytes.

Intensity and drivers of subtypes interference between seasonal influenza viruses in mainland China: A modeling study.

Subtype interference has a significant impact on the epidemiological patterns of seasonal influenza viruses (SIVs). We used attributable risk percent [the absolute value of the ratio of the effective reproduction number (Rₑ) of different subtypes minus one] to quantify interference intensity between A/H1N1 and A/H3N2, as well as B/Victoria and B/Yamagata. The interference intensity between A/H1N1 and A/H3N2 was higher in southern China 0.26 (IQR: 0.11-0.46) than in northern China 0.17 (IQR: 0.07-0.24). Similarly, interference intensity between B/Victoria and B/Yamagata was also higher in southern China 0.14 (IQR: 0.07-0.24) than in norther China 0.10 (IQR: 0.04-0.18). High relative humidity significantly increased subtype interference, with the highest relative risk reaching 20.59 (95% CI: 6.12-69.33) in southern China. Southern China exhibited higher levels of subtype interference, particularly between A/H1N1 and A/H3N2. Higher relative humidity has a more pronounced promoting effect on subtype interference.

Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOCs) are the most common craniofacial malformation. In the complex aetiology and pathogenesis of NSOCs, genetic factors play a crucial role and IRF6, located at chromosome 1q32.2, is the best documented NSOC susceptibility gene. IRF6 is a key factor in oral maxillofacial development and known to contribute the most in NSOCs. It is essential to conduct a complete review of the existing results on IRF6 to further understand its role in the pathogenesis of NSOCs. Thus, the present authors summarised the research progress on the mechanism of IRF6 in NSOCs from both genetic and functional perspectives in this review.

Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis.

OBJECTIVE: Tumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells. METHODS: Stem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool "ConsensusClusterPlus." Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model's clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes. RESULTS: Utilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature's independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues. CONCLUSION: The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.

Glycosylation-related genes mediated prognostic signature contribute to prognostic prediction and treatment options in ovarian cancer: based on bulk and single­cell RNA sequencing data.

BACKGROUND: Ovarian cancer (OC) is a complex disease with significant tumor heterogeneity with the worst prognosis and highest mortality among all gynecological cancers. Glycosylation is a specific post-translational modification that plays an important role in tumor progression, immune escape and metastatic spread. The aim of this work was to identify the major glycosylation-related genes (GRGs) in OC and construct an effective GRGs signature to predict prognosis and immunotherapy. METHODS: AUCell algorithm was used to identify glycosylation-related genes (GRGs) based on the scRNA-seq and bulk RNA-seq data. An effective GRGs signature was conducted using COX and LASSO regression algorithm. The texting dataset and clinical sample data were used to assessed the accuracy of GRGs signature. We evaluated the differences in immune cell infiltration, enrichment of immune checkpoints, immunotherapy response, and gene mutation status among different risk groups. Finally, RT-qPCR, Wound-healing assay, Transwell assay were performed to verify the effect of the CYBRD1 on OC. RESULTS: A total of 1187 GRGs were obtained and a GRGs signature including 16 genes was established. The OC patients were divided into high- and low- risk group based on the median riskscore and the patients in high-risk group have poor outcome. We also found that the patients in low-risk group have higher immune cell infiltration, enrichment of immune checkpoints and immunotherapy response. The results of laboratory test showed that CYBRD1 can promote the invasion, and migration of OC and is closely related to the poor prognosis of OC patients. CONCLUSIONS: Our study established a GRGs signature consisting of 16 genes based on the scRNA-seq and bulk RNA-seq data, which provides a new perspective on the prognosis prediction and treatment strategy for OC.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

Shuangshen ningxin formula attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial function.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen Ningxin Formula (SSNX) is a traditional Chinese medicine formula used to treat myocardial ischemia-reperfusion injury (MIRI). A randomized controlled trial previously showed that SSNX reduced cardiovascular events, and experiments have also verified that SSNX attenuated ischemia-reperfusion (I/R) injury. However, the mechanism of SSNX in the treatment of microvascular I/R injury is still unclear. AIM OF THE STUDY: To determine whether SSNX protects the microvasculature by regulating I/R induction in rats and whether this effect depends on the regulation of NR4A1/Mff/Drp1 pathway. METHODS: The anterior descending coronary artery was ligated to establish a rat MIRI model with 45 min of ischemia and 24 h of reperfusion. The rats were subjected to a 7-day pretreatment with SSNX and nicorandil, after which their cardiac function and microvascular functional morphology were evaluated through diverse methods, including hematoxylin and eosin (HE) staining, wheat germ agglutinin (WGA) staining, and transmission electron microscopy. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Additionally, serum levels of ET-1 and eNOS were determined through an enzyme-linked immunosorbent assay (ELISA). The expression levels of NR4A1, Mff, and proteins related to mitochondrial fission were examined by Western blot (WB). Cardiac microcirculation endothelial cells (CMECs) were cultured and the oxygen-glucose deprivation/reoxygenation (OGD/R) model was duplicated. Following treatment with SSNX and DIM-C-pPhOH, an NR4A1 inhibitor, cell viability was assessed. Fluorescence was used to evaluate mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening. Moreover, vascular endothelial function was evaluated through transendothelial electrical resistance (TEER), Transwell assays and tube formation assays. RESULTS: The results showed that SSNX reduced the infarction area and no-flow area, improved cardiac function, mitigated pathological alterations, increased endothelial nitric oxide synthase expression, protected endothelial function, and attenuated microvascular damage after I/R injury. I/R triggered mitochondrial fission and apoptotic signaling in CMECs, while SSNX restored mitochondrial fission to normal levels and inhibited mitochondrial apoptosis. A study using CMECs revealed that SSNX protected endothelial function after OGD/R, attenuating the increase in NR4A1/Mff/Drp1 protein and inactivating VDAC1, HK2, cytochrome c (cyt-c) and caspase-9. Research also shows that SSNX can affect CMEC cell migration and angiogenesis, reduce mitochondrial membrane potential damage, and inhibit membrane opening. Moreover, DIM-C-pPhOH, an NR4A1 inhibitor, partially imitated the effect of SSNX. CONCLUSION: SSNX has a protective effect on the cardiac microvasculature by inhibiting the NR4A1/Mff/Drp1 pathway both in vivo and in vitro.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

Long-term effects of transcranial direct current stimulation (tDCS) combined with speech language therapy (SLT) on post-stroke aphasia patients: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation tool for improving language performance in patients with aphasia after stroke. However, it remains unclear whether it has long-term effects. After consulting a large number of relevant studies, it was found that there are no definitive conclusions about the long-term effects of tDCS on post-stroke aphasia patients. OBJECTIVE: To determine whether tDCS has long-term effects on post-stroke aphasia patients (PAPs) and which type of tDCS has the most beneficial treatment effects on language performance (especially naming ability). METHODS: A network meta-analysis was conducted by searching for randomized controlled trials (RCTs) published until April 2023 in the following databases: Web of Science, Embase, Medline (from OVID and PubMed), PsycInfo and PsycARTICLES (from OVID). We only included RCTs published in English. PAPs treated by tDCS combined with speech-language therapy were selected. Sham tDCS was the control group. Naming ability or other language performance must be assessed at follow-up states. Two reviewers independently used checklists to assess the primary outcome (the long-term effects on naming ability) and the secondary outcome (other language performance, such as communication). Cochrane Collaboration guidelines were used to assess the risk of bias. RESULTS: Seven studies with 249 patients were included for data synthesis. For primary outcomes (naming nous), there was no obvious evidence to show a difference between interventions (C-tDCS vs. S-tDCS SMD = 0.06, 95% CI = -1.01, 1.12; A-tDCS vs. S-tDCS SMD = 0.00, 95% CI = -0.66, 0.65; D-tDCS vs. S-tDCS SMD = 0.77, 95% CI = -0.71, 2.24; A-tDCS vs. C-tDCS SMD = -0.06, 95% CI = -1.31,1.19; D-tDCS vs. C-tDCS SMD = 0.71, 95% CI = -1.11,2.53; D-tDCS vs. A-tDCS SMD = 0.77, 95% CI = -0.84, 2.39). In addition, no evidence showed differences in communication ability (C-tDCS vs. S-tDCS SMD = 0.08 95% CI = -1.77, 1.92; A-tDCS vs. S-tDCS SMD = 1.23 95% CI = -1.89, 4.34; D-tDCS vs. S-tDCS SMD = 0.70; 95% CI = -1.93, 3.34; A-tDCS vs. C-tDCS SMD = 1.15 95% CI = -2.48, 4.77; D-tDCS vs. C-tDCS SMD = 0.62 95% CI = -2.59, 3.84; D-tDCS vs. A-tDCS SMD = -0.52 95% CI = -4.60, 3.56). CONCLUSION: It seems that tDCS has no long-term effects on post-stroke aphasia patients in naming nouns and communication in terms of the results of our network meta-analysis. However, the results should be interpreted with caution. In the future, more RCTs with long follow-up times should be included in the research to conduct subgroup or meta-regression analyses to obtain a sufficient effect size.

[Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction].

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Prevalence of hepatitis E virus in China from 1997 to 2022: a systematic review and meta-analysis.

Introduction: Several studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors. Methods: We included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural-urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections. Results: The pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23-26.25], 0.73% (95% CI: 0.55-0.93), 0.12% (95% CI: 0.01-0.32), and 6.55% (95% CI: 3.46-12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02-56.85) and older adult aged 50-59 years (40.87%; 95% CI: 31.95-50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50-2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17-1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29-1.73) were risk factors of anti-HEV IgG seroprevalence. Discussions: Overall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.

Relationship between ocular surface pain and corneal nerve loss in dry eye diabetics: a cross-sectional study in Shenyang, China.

BACKGROUND: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED pathology. OBJECTIVE: To investigate the potential relationship between corneal nerve loss and ocular pain among diabetic patients with dry eye (DE). DESIGN: A cross-sectional study. SETTING: He Eye Specialist Hospital, Shenyang, China. PARTICIPANTS: This study recruited 124 eyes of 62 diabetic patients diagnosed with DED between August and October 2022. MAIN OUTCOME MEASURES: Best-corrected visual acuity, intraocular pressure, non-invasive tear breakup time, tear meniscus height, tear film lipid layer, conjunctival hyperaemia (redness score), conjunctivocorneal epithelial staining (CS score), central corneal sensitivity and vitro confocal corneal microscopy was assessed in all subjects. The Ocular Surface Disease Index Questionnaire assessed DE symptoms and ocular pain. RESULTS: The study's final analysis included 26 patients (52 eyes) without ocular pain and 36 patients (72 eyes) with ocular pain. The corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) in patients with ocular pain were significantly lower than those without (p<0.001, p=0.004, and p<0.001, respectively). CNFD, CNBD and CNFL negatively correlated with ocular pain (r=-0.385, r=-0.260, r=-0.358, respectively). Moreover, CNFD, CNBD and CNFL have a significant (p<0.05) positive correlation with corneal sensitivity (r=0.523, r=0.330, r=0.421, respectively). CONCLUSIONS: Corneal nerve loss was associated with ocular pain and decreased corneal sensitivity in diabetic patients with DE. Further studies into the neurological role of ocular surface diseases can elaborate diagnostics, prognosis and treatment of diabetic patients with DE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05193331).

The Combined Impact of Intense Pulsed Light Combined and 3% Diquafosol Ophthalmic Solution on Evaporative Dry Eye: A Randomized Control Study.

INTRODUCTION: The primary objective of this study is to assess whether the combination of intense pulsed light (IPL) with 3% diquafosol (DQS) ophthalmic solution is more effective than intense pulsed light in alleviating signs and symptoms of dry eye disease (DED). METHODS: This randomized study included 66 participants with evaporative dry eye (EDE) who received IPL + DQS therapy (n = 44 eyes), IPL therapy (n = 44 eyes), or sham therapy (n = 44 eyes). All participants were examined at baseline (D0), day 14 (D14), and day 28 (D28) for non-invasive break-up time (NITBUT), tear-film lipid layer (TFLL), corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expression (MGEx), and ocular surface disease index (OSDI). RESULTS: At day 28, comparison among the IPL + DQS therapy, IPL therapy, and sham therapy found significant differences in the mean NITBUT (12.03 ± 1.27 versus 10.47 ± 3.48 versus 4.57 ± 0.46; p < 0.001), TFLL (2.09 ± 0.29 versus 2.27 ± 0.45 versus 2.89 ± 0.65; p < 0.001), CS (1.43 ± 0.82 versus 1.93 ± 1.32 versus 3.52 ± 1.00; p < 0.001), MGQ (1.55 ± 0.66 versus 1.91 ± 0.77 versus 2.66 ± 0.53; p < 0.001), MGEx (1.27 ± 0.45 versus 1.75 ± 0.44 versus 2.41 ± 0.50; p < 0.001), and OSDI score (19.36 ± 7.01 versus 24.77 ± 4.68 versus 42.61 ± 7.49; p < 0.001); significant improvements in NITBUT, TFLL, CS, MGQ, MGEx, and OSDI were found in the IPL + DQS therapy and IPL therapy, while the sham therapy had no significant improvements. CONCLUSION: Combining 3% diquafosol ophthalmic solution with intense pulsed light was superior to IPL therapy alone in relieving the signs and symptoms of patients with severe evaporative DED. TRIAL REGISTRATION: Clinical Trials Identifier: NCT05694026.

Global burden and trends of respiratory syncytial virus infection across different age groups from 1990 to 2019: A systematic analysis of the Global Burden of Disease 2019 Study.

OBJECTIVE: Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies. METHODS: Data on RSV-related burden were extracted from the Global Burden of Disease 2019. Joinpoint regression models were used to assess the global temporal trends of RSV and further stratified analyses were conducted according to the Socio-demographic Index (SDI), which is a composite measure of income, education, and total fertility. Age-period-cohort model was used to evaluate age, period, and cohort effects. RESULTS: In 2019, the global age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASR-DALYs) of RSV were 4.79/100,000 (95% uncertainty interval [95% UI]: 1.82/100,000-9.32/100,000) and 218.34/100,000 (95% UI: 92.06/100,000-376.80/100,000), respectively. The burden of RSV was higher in men than women. The highest ASMR (10.26/100,000, 3.80/100,000-20.16/100,000) and ASR-DALYs (478.71/100,000, 202.40/100,000-840.85/100,000) were reported in low-SDI region. Although mortality and DALYs rates in all age groups declined globally, the pace of decline was not uniform across age groups. Mortality rate in the elderly over 70 years surpassed that in children under 5 years in 2019. CONCLUSION: This study highlights the need for targeted interventions to reduce the burden of RSV, particularly in low-SDI region, and among the elderly over 70 years.

Gut microbiome biomarkers in adolescent obesity: a regional study.

Purpose: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome. Methods: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition. Results: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders. Conclusions: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.

Zeolitic Imidazolate Framework-8 (ZIF-8) as a Drug Delivery Vehicle for the Transport and Release of Telomerase Inhibitor BIBR 1532.

Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR 1532@ZIF-8 were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR 1532@ZIF-8-treated cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.