Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

Accuracy of the COMPASS-CAT thrombosis risk assessment scale in predicting venous thromboembolism in cancer patients: a meta-analysis.

OBJECTIVE: This systematic review aims to assess the accuracy of the COMPASS-CAT tool in predicting venous thromboembolism (VTE) among cancer patients. METHODS: Relevant studies were searched in PubMed, Web of Science, The Cochrane Library, Embase, CINAHL, OVID, CBM, CNKI, WanFang Data, and VIP database from their inception up to April 19, 2023. The quality of studies was appraised using the diagnostic test accuracy study bias assessment tool (QUADAS-2). Quantitative analysis was performed using Stata MP 17.0. RESULTS: Thirteen studies involving 8,665 patients were included. Meta-analysis indicated that the COMPASS-CAT score had a pooled sensitivity of 0.76 [95%CI (0.61, 0.86)], specificity of 0.67 [95%CI (0.52, 0.79)], positive likelihood ratio of 2.3 [95%CI (1.7, 3.1)], negative likelihood ratio of 0.36 [95%CI (0.23, 0.54)], diagnostic odds ratio of 6 [95%CI (4, 10)], and an area under the Summary Receiver Operating Characteristic (SROC) curve (AUC) of 0.77 [95%CI (0.74, 0.81)]. Funnel plots indicated no publication bias. Meta-regression and subgroup analysis suggested that country and diagnostic setting might be potential sources of heterogeneity. The sensitivity of the COMPASS-CAT assessment tool in international outpatient settings was 0.94 with an AUC of 0.86, while in domestic inpatient settings, the sensitivity was 0.65 with an AUC of 0.78. CONCLUSION: The COMPASS-CAT score had a certain diagnostic value for VTE in cancer patients and can effectively identify patients at risk of VTE. Most studies focus on patients with lung cancer. Future research should investigate more tumor types, and high-quality, large-sample, multi-center prospective studies on larger populations with cancers are warranted.

Postoperative effect of sufentanil preemptive analgesia combined with psychological intervention on breast cancer patients.

OBJECTIVES: To explore the postoperative effects of sufentanil preemptive analgesia combined with psychological intervention on breast cancer patients undergoing radical surgery. METHODS: 112 female breast cancer patients aged 18-80 years old who underwent radical surgery by the same surgeon were randomly divided into 4 groups, and there were 28 patients in each group. Patients in group A were given 10 µg sufentanil preemptive analgesia combined with perioperative psychological support therapy (PPST), group B had only 10 µg sufentanil preemptive analgesia, group C had only PPST, and group D were under general anesthesia with conventional intubation. Visual analogue scoring (VAS) was used for analgesic evaluation at 2, 12 and 24 h after surgery and compared among the four groups by ANOVA method. RESULTS: The awakening time of patients in group A or B was significantly shorter than that in group C or D, and the awakening time in group C was significantly shorter than that in group D. Moreover, patients in group A had the shortest extubation time, while the group D had the longest extubation time. The VAS scores at different time points showed significant difference, and the VAS scores at 12 and 24 h were significantly lower than those at 2 h (P < 0.05). The VAS scores and the changing trend of VAS scores were varied among the four groups (P < 0.05). In addition, we also found that patients in group A had the longest time to use the first pain medication after surgery, while patients in group D had the shortest time. But the adverse reactions among the four groups showed no difference. CONCLUSIONS: Sufentanil preemptive analgesia combined with psychological intervention can effectively relieve the postoperative pain of breast cancer patients.

A meta-analysis of randomized controlled trials on therapeutic efficacy and safety of autologous cell therapy for atherosclerosis obliterans.

OBJECTIVE: Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for "no-option" patients, and stem cell therapy is considered a viable option, although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO. METHODS: We performed a literature search of published randomized controlled trials (RCTs) for patients with ASO receiving stem cell therapy without a revascularization option. PubMed, Embase, and the Cochrane Library were searched. This study was conducted by a pair of authors independently and audited by a third author. Data were synthesized with a random-effects model. RESULTS: A total of 630 patients in 12 RCTs were included. The results showed that cell therapy significantly improved total amputation (relative risk [RR], 0.64; 95% confidence interval [CI], 0.47-0.87; P = .004), major amputation (RR, 0.69; 95% CI, 0.50-0.94; P = .02), ankle-brachial index (mean difference [MD], 0.08; 95% CI, 0.02-0.13; P = .004), transcutaneous oxygen tension (MD, 11.52; 95% CI, 3.60-19.43; P = .004), and rest pain score (MD, -0.64; 95% CI, -1.10 to -0.17; P = .007) compared with placebo or standard care. However, current studies showed cell therapy was not superior to placebo or standard care in all-cause death (RR, 0.75; 95% CI, 0.41-1.36; P = .34) and ulcer size (MD, -8.85; 95% CI, -29.05 to 11.36; P = .39). The number of trials included was limited. Moreover, most trials were designed for "no-option" patients, and thus the results should be applied with caution to other patients with peripheral arterial disease. CONCLUSIONS: Patients with ASO can benefit from autologous cell therapy in limb salvage, limb blood perfusion, and rest pain alleviation.

Ceramide subclasses identified as novel lipid biomarker elevated in women with polycystic ovary syndrome: a pilot study employing shotgun lipidomics.

This study aimed to identify potential lipid biomarkers in women with polycystic ovary syndrome (PCOS) and determine their predictive value for PCOS. Eighteen women with PCOS and 17 healthy controls were enrolled. A multi-dimensional mass spectrometry-based shotgun lipidomics approach was employed to analyze serum lipid profiles. Shotgun lipidomics revealed that the concentrations of ceramide (Cer) and phosphatidylcholine (PC) were higher (PC: 831.6 ± 217.4 vs. 605.2 ± 164.2 µmol/l; Cer: 3,387.6 ± 829.9 vs. 2,552.2 ± 679.4 nmol/l, respectively), whereas that of lysophosphatidylcholine was lower, in PCOS women than in healthy controls (82.02 ± 39.49 vs. 133.62 ± 65.36 µmol/l, respectively). Receiver operating characteristic analysis showed that the combination of Cer (OH_N16:0/N18:0) and Cer (N22:0) had the greatest discriminatory power to differentiate between women with and without PCOS (area under the curve: 0.889, 95% confidence interval: 0.784-0.994). These results indicate that the combination of Cer (OH_N16:0/N18:0) and Cer (N22:0) may represent a novel lipid predictor of PCOS.

Different effects of etomidate and propofol on memory in immature rats.

This study is to investigate the effects of etomidate and propofol on memory and possible involved mechanisms using immature rats. Forty-eight rats randomly received intraperitoneal injection of 5 mg/kg etomidate (n = 16), 50 mg/kg propofol (n = 16) or normal saline (control, n = 16). Three hours after awakening, memory was assessed by Y-maze test using 10 rats in each drug group. Gamma-aminobutyric acid (GABA) content in hippocampal tissue was measured using six rats in each group. Etomidate group had more total reaction time (TRT) compared with the control group in Y-maze test ( p < 0.05). No other difference between these two groups was observed. Propofol group had less number of correct response ( p < 0.01) and more TRT ( p < 0.05) in Y-maze test, as well as more GABA concentration detected in hippocampal tissue ( p < 0.01) than the control group. Propofol group also showed less number of correct response ( p < 0.05) and more hippocampal GABA concentration ( p < 0.01) compared with etomidate group. Etomidate does not show significant effects on memory in rat and further investigation is required. Propofol can affect memory in rat possibly via increasing the synthesis and/or secretion of GABA as one of the factors.

Leveraging multimodal MRI-based radiomics analysis with diverse machine learning models to evaluate lymphovascular invasion in clinically node-negative breast cancer.

Objective: This study aimed to investigate and validate the effectiveness of diverse radiomics models for preoperatively differentiating lymphovascular invasion (LVI) in clinically node-negative breast cancer (BC). Methods: This study included 198 patients diagnosed with clinically node-negative bc and pathologically confirmed LVI status from January 2018-July 2023. The training dataset consisted of 138 patients, while the validation dataset included 60. Radiomics features were extracted from multimodal magnetic resonance imaging obtained from T1WI, T2WI, DCE, DWI, and ADC sequences. Dimensionality reduction and feature selection techniques were applied to the extracted features. Subsequently, machine learning approaches, including logistic regression, support vector machine, classification and regression trees, k-nearest neighbors, and gradient boosting machine models (GBM), were constructed using the radiomics features. The best-performing radiomic model was selected based on its performance using the confusion matrix. Univariate and multivariable logistic regression analyses were conducted to identify variables for developing a clinical-radiological (Clin-Rad) model. Finally, a combined model incorporating both radiomics and clinical-radiological model features was created. Results: A total of 6195 radiomic features were extracted from multimodal magnetic resonance imaging. After applying dimensionality reduction and feature selection, seven valuable radiomics features were identified. Among the radiomics models, the GBM model demonstrated superior predictive efficiency and robustness, achieving area under the curve values (AUC) of 0.881 (0.823,0.940) and 0.820 (0.693,0.947) in the training and validation datasets, respectively. The Clin-Rad model was developed based on the peritumoral edema and DWI rim sign. In the training dataset, it achieved an AUC of 0.767 (0.681, 0.854), while in the validation dataset, it achieved an AUC of 0.734 (0.555-0.913). The combined model, which incorporated radiomics and the Clin-Rad model, showed the highest discriminatory capability. In the training dataset, it had an AUC value of 0.936 (0.892, 0.981), and in the validation dataset, it had an AUC value of 0.876 (0.757, 0.995). Additionally, decision curve analysis of the combined model revealed its optimal clinical efficacy. Conclusion: The combined model, integrating radiomics and clinical-radiological features, exhibited excellent performance in distinguishing LVI status. This non-invasive and efficient approach holds promise for aiding clinical decision-making in the context of clinically node-negative BC.

Association of Fat Mass and Skeletal Muscle Mass with Cardiometabolic Risk Varied in Distinct PCOS Subtypes: A Propensity Score-Matched Case-Control Study.

(1) Background: polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome with a constellation of cardiometabolic risk factors. We aimed to investigate if the association of body fat mass (BFM) and skeletal muscle mass (SMM) with cardiometabolic risk differed in PCOS subtypes. (2) Methods: 401 participants (245 PCOS and 156 controls) were assessed for anthropometric measurements, glucose-lipid profiles, reproductive hormones and body composition with propensity score-matched (PSM) analysis. The association of the cardiometabolic risk score (z score, calculated based on levels of obesity and gluco-lipid measurements) with BFM (estimated by trunk BFM/Height2) and SMM (estimated by SMM/Height2) was calculated. (3) Results: Trunk BFM/Height2 and SMM/Height2 were both positively associated with cardiometabolic risk in PCOS (trunk BFM/Height2, OR 2.33, 95% CI 1.49-3.65; SMM/Height2, OR 2.05, 95% CI 1.12-3.76). SMM/Height2 associated with increased cardiometabolic risk in obese PCOS (BMI ≥ 28 kg/m2, OR 2.27, 95% CI 1.15-4.47). For those with lower BMI (<28 kg/m2), trunk BFM/Height2 showed a higher OR in both groups (PCOS, OR 2.12, 95% CI 1.06-4.24; control 2.04, 95% CI 1.04-4.02). Moreover, distinct associations among BMI-stratified groups were validated in hierarchical clustering identifying metabolic and reproductive clusters. (4) Conclusions: BFM and SMM are synergistically associated with higher cardiometabolic risk in PCOS women. Although BFM contributes to increased cardiometabolic risk, SMM also plays a primary role in obese PCOS. Our results highlight the importance of body composition in the management of PCOS.

A New Mouse Model for Usher Syndrome Crossing Kunming Mice with CBA/J Mice.

BACKGROUND: Previously, we discovered a strain of Kunming mice, referred to as the KMush/ush strain, that exhibited notably abnormal electroretinogram (ERG) readings and elevated thresholds for auditory brainstem responses (ABRs), which resembled the characteristics of Usher Syndrome (USH). We successfully identified the pathogenic genes, Pde6b and Adgrv1, after KMush/ush crossbred with CBA/CaJ mice, referred to as CBA-1ush/ush, CBA-2ush/ush or CBA-2ush/ush. In this investigation, we crossbred KMush/ush and CBA/J mice to establish novel recombinant inbred lines and analysed their phenotypic and genotypic characteristics. METHODS: ERG readings, ABR testing, fundus morphology, histological examination of the retina and inner ear, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, western blotting, DNA sequence analysis and behavioural experiments were performed to assess the phenotypes and genotypes of the progeny lines. RESULTS: No obvious waveforms in the ERG were detected in F1 hybrid mice while normal ABR results were recorded. The F2 hybrids, which were called J1ush/ush or J2ush/ush, exhibited segregated hearing-loss phenotypes. J1ush/ush mice had a retinitis pigmentosa (RP) phenotype with elevated ABR thresholds, whereas J2ush/ush mice exhibited only the RP phenotype. Interestingly, J1ush/ush mice showed significantly higher ABR thresholds than wild-type mice at 28 days post born (P28), and RT-qPCR and DNA-sequencing analysis showed that Adgrv1 gene expression was significantly altered in J1ush/ush mice, but histological analysis showed no significant structural changes in the organ of Corti or spiral ganglia. Further elevation of ABR-related hearing thresholds by P56 manifested only as a reduced density of spiral ganglion cells, which differed significantly from the previous pattern of cochlear alterations in CBA-2ush/ush mice. CONCLUSIONS: We successfully introduced the hearing-loss phenotype of inbred mice with USH into CBA/J mice, which provides a good animal model for future studies on the important physiological roles of the Adgrv1 gene in inner-ear structure and for therapeutic studies targeting Adgrv1-mutated USH.

Integrative multi-omics analyses reveal vesicle transport as a potential target for thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) refers to dilation and enlargement of the thoracic aorta caused by various reasons. Most patients have no apparent symptoms in the early stage and are subject to a poor prognosis once the aneurysm ruptures. It is crucial to identify individuals who are predisposed to TAA and to discover effective therapeutic targets for early intervention. METHODS: We conducted a label-free quantitative proteomic analysis among aorta tissue samples from TAA patients to screen differentially expressed proteins (DEPs) and key co-expression modules. Two datasets from Gene Expression Omnibus (GEO) database were included for integrative analysis, and the identified genes were subjected to immunohistochemistry (IHC) validation. Detailed vesicle transport related enrichment analysis was conducted and two FDA-approved drugs, chlorpromazine (CPZ) and chloroquine (CQ), were selected for in vivo inhibition of vesicle transport in mice TAA model. The diameter of thoracic aorta, mortality and histological differences after interventions were evaluated. RESULTS: We found significant enrichments in functions involved with vesicle transport, extracellular matrix organizing, and infection diseases in TAA. Endocytosis was the most essential vesicle transport process in TAA formation. Interventions with CPZ and CQ significantly reduced the aneurysm diameter and elastin degradation in vivo and enhanced the survival rates of TAA mice. CONCLUSIONS: We systematically screened the aberrantly regulated bioprocesses in TAA based on integrative multi-omics analyses, identified and demonstrated the importance of vesicle transport in the TAA formation. Our study provided pilot evidence that vesicular transport was a potential and promising target for the treatment of TAA.

Association between PLA2R gene polymorphism and idiopathic membranous nephropathy in Heilongjiang Chinese.

Background: The aim of this study was to investigate the correlation between the phospholipase A2 receptor (PLA2R) gene polymorphism and idiopathic membranous nephropathy (IMN) in Heilongjiang Chinese. Methods: Thirty-five patients with IMN confirmed by renal biopsy attending the Heilongjiang Hospital of Traditional Chinese Medicine between June 2021 and December of 2021 were selected as the IMN group, and a group of 25 healthy participants from the Physical Examination Center of Heilongjiang Hospital of Traditional Chinese Medicine were enrolled as healthy controls. Polymerase chain reaction (PCR) was used to identify and genotype 8 single-nucleotide polymorphism (SNP) loci (rs16844715, rs2715918, rs2715928, rs35771982, rs3749119, rs3828323, rs4665143, and rs6757188) of PLA2R and to analyze the PLA2R gene polymorphisms that correlated with IMN. SPSS 26.0 statistical software was used for data analysis, and the chi-squared (χ2) goodness-of-fit test was used to determine whether each SNP genotype and allele in the PLA2R gene complied with the Hardy-Weinberg equilibrium. The qualitative data were analyzed via χ2 or Fisher exact probability method. Logistic regression was used to analyze risk factors, and the odds ratios (ORs) values and 95% confidence intervals (CIs) were calculated. α=0.05 was taken as the test level, and P<0.05 was considered statistically significant. Results: Statistically significant differences were found in the genotype and allele frequencies of rs35771982 and rs3749119 between the IMN and control groups (P<0.05). Logistic regression analysis showed that the genotypes rs35771982 GG and rs3749119 CC were associated with IMN susceptibility. Statistically significant differences in uric acid level were found between the rs35771982 GG and CG + CC genotypes (P<0.05), while statistically significant differences in serum albumin were detected between rs3749119 CC and the CT + TT genotypes (P<0.05). Multivariate logistic regression analysis showed that gender, age, and triglyceride levels affected the occurrence of IMN (P<0.05). Conclusions: The PLA2R gene polymorphisms rs35771982 and rs3749119 in Heilongjiang Chinese may be related to IMN susceptibility and correlated with clinical indicators of IMN. Gender, age, and triglyceride levels may influence the occurrence of IMN.

Transcriptomic analysis of the cerebral hippocampal tissue in spontaneously hypertensive rats exposed to acute hypobaric hypoxia: associations with inflammation and energy metabolism.

We evaluated the effect of acute hypobaric hypoxia (AHH) on the hippocampal region of the brain in early-stage spontaneously hypertensive male rats. The rats were classified into a control (ground level; ~ 400 m altitude) group and an AHH experimental group placed in an animal hypobaric chamber at a simulated altitude of 5500 m for 24 h. RNA-Seq analysis of the brains and hippocampi showed that differentially expressed genes (DEGs) were primarily associated with ossification, fibrillar collagen trimer, and platelet-derived growth factor binding. The DEGs were classified into functional categories including general function prediction, translation, ribosomal structure and biogenesis, replication, recombination, and repair. Pathway enrichment analysis revealed that the DEGs were primarily associated with relaxin signaling, PI3K-Akt signaling, and amoebiasis pathways. Protein-protein interaction network analysis indicated that 48 DEGs were involved in both inflammation and energy metabolism. Further, we performed validation experiments to show that nine DEGs were closely associated with inflammation and energy metabolism, of which two (Vegfa and Angpt2) and seven (Acta2, Nfkbia, Col1a1, Edn1, Itga1, Ngfr, and Sgk1) genes showed up and downregulated expression, respectively. Collectively, these results indicated that inflammation and energy metabolism-associated gene expression in the hippocampus was altered in early-stage hypertension upon AHH exposure.

An H2 S-BMP6 Dual-Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy.

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO-66-NH2 @GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti-oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO-66-NH2 @GYY4137@BMP6 dual-loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser-doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO-66-NH2 @GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas-protein synergistic therapy.

A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment.

Immunomodulatory therapy has become a promising method for the clinical treatment of many diseases. Recently, pilot studies revealed that immunomodulatory therapy exhibited good effects on the treatment of cardiovascular diseases, but many problems remain to be solved, such as useful platforms for drug co-delivery and combination therapies. In this study, we designed and constructed the multifunctional nanoparticle Rapa@UiO-66-NH-FAM-IL-1Ra (RUFI) for the treatment of atherosclerotic cardiovascular disease. This nanoplatform combined the advantages of metal-organic frameworks (MOFs) for drug co-delivery, rapamycin and IL-1Ra for immunomodulation, IL-1Ra for cellular targeting, and 5-FAM for fluorescence imaging. RUFI exhibited good drug release of rapamycin and IL-1Ra and specific cytotoxicity for inflammatory macrophages in vitro. In an atherosclerotic model of diet-fed ApoE-/- mice, RUFI significantly targeted and reduced atherosclerosis plaques in coronary arteries, carotid arteries, and aortas. Mechanistic studies indicated that RUFI modulated macrophage phenotype, cytokine expression, and autophagy. This study demonstrated that combination therapy with rapamycin and IL-1Ra via MOF carriers enhanced the immunoregulatory effects against atherosclerosis. This drug co-delivery system suggests that MOF carriers loaded with immunomodulators are promising treatments for atherosclerosis or other inflammatory diseases.

The Importance of Clinical Pharmacists in Improving Blood Glucose and Lipid Levels in Patients with Diabetes and Myocardial Infarction.

Purpose: The aim of this study was to evaluate whether intervention by clinical pharmacists can improve blood glucose and lipid levels in diabetic patients with complex medical conditions. Methods: The retrospective database included 138 patients with diabetes who had presented with acute myocardial infarction (AMI) between January 2019 and October 2021. Blood glucose and lipid levels were measured within 12 weeks and 78 weeks of follow-up. Propensity score matching (PSM) was used to balance the confounding effects of patients' characteristics. Results: A total of 138 eligible patients were assigned to either the intervention group (n = 47) or the usual care group (n = 91). After the intervention, there were significant improvements in blood glucose (glycosylated hemoglobin-HbA1C % from 9.0 to 8.3; fasting blood glucose-FBG mmol/L from 11.3 to 7.1; postprandial blood glucose-PBG mmol/L from 17.0 to 12.1; p < 0.001) and lipid levels (total cholesterol-TC from 4.9 to 3.5, low-density lipoprotein cholesterol-LDL-C from 3.0 to 1.8, p < 0.001, mmol/L) in both follow-up periods. The blood glucose effects were most pronounced in the PBG control rate (76.9% vs 54.0%) before PSM, while HbA1C% and PBG control rate after PSM were significantly higher in the intervention group (HbA1C% rate: 65.6% vs 38.5%; PBG rate: 79.2% vs 45.8%; p < 0.05, intervention vs non-intervention). Subgroup analysis further confirmed the improvement of blood glucose and lipid mainly in patients with higher baseline FBG (≧10mmol/L) and moderate follow-up duration (4-12 weeks). Conclusion: The intervention of clinical pharmacists in multidisciplinary team can significantly improve blood glucose and lipid levels in complex type 2 diabetic patients, especially those with high baseline FBG and moderate follow-up durations.

m6A Modification Mediates Endothelial Cell Responses to Oxidative Stress in Vascular Aging Induced by Low Fluid Shear Stress.

N6-methyladenosine (m6A) is one of the most prevalent, abundant, and internal transcriptional modification and plays essential roles in diverse cellular and physiological processes. Low fluid shear stress (FSS) is a key pathological factor for many cardiovascular diseases, which directly forces on the endothelial cells of vessel walls. So far, the alterations and functions of m6A modifications in vascular endothelial cells at the low FSS are still unknown. Herein, we performed the transcriptome-wide m6A modification profiling of HUVECs at different FSS. We found that the m6A modifications were altered earlier and more sensitive than mRNA expressions in response to FSS. The low FSS increased the m6A modifications at CDS region but decreased the m6A modifications at 3' UTR region and regulated both the mRNA expressions and m6A modifications of the m6A regulators, such as the RBM15 and EIF3A. Functional annotations enriched by the hypermethylated and hypomethylated genes at low FSS revealed that the m6A modifications were clustered in the aging-related signaling pathways of mTOR, PI3K-AKT, insulin, and ERRB and in the oxidative stress-related transcriptional factors, such as HIF1A, NFAT5, and NFE2L2. Our study provided a pilot view of m6A modifications in vascular endothelial cells at low FSS and revealed that the m6A modifications driven by low FSS mediated the cellular responses to oxidative stress and cell aging, which suggested that the m6A modifications could be the potential targets for inhibiting vascular aging at pathological low FSS.

Influence and mechanism of sodium-glucose cotransporter-2 inhibitors on the cardiac function: study protocol for a prospective cohort study.

Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.

Simulated vestibular spatial disorientation mouse model under coupled rotation revealing potential involvement of Slc17a6.

Spatial disorientation (SD) is the main contributor to flight safety risks, but research progress in animals has been limited, impeding a deeper understanding of the underlying mechanisms of SD. This study proposed a method for constructing and evaluating a vestibular SD mouse model, which adopted coupled rotational stimulation with visual occlusion. Physiological parameters were measured alongside behavioral indices to assess the model, and neuronal changes were observed through immunofluorescent staining. The evaluation of the model involved observing decreased colonic temperature and increased arterial blood pressure in mice exposed to SD, along with notable impairments in motor and cognitive function. Our investigation unveiled that vestibular SD stimulation elicited neuronal activation in spatially associated cerebral areas, such as the hippocampus. Furthermore, transcriptomic sequencing and bioinformatics analysis revealed the potential involvement of Slc17a6 in the mechanism of SD. These findings lay a foundation for further investigation into the molecular mechanisms underlying SD.

Nuciferine Protects Against High-Fat Diet-Induced Hepatic Steatosis via Modulation of Gut Microbiota and Bile Acid Metabolism in Rats.

Our previous study showed that nuciferine (NF) attenuated non-alcoholic fatty liver disease (NAFLD), which is attributed to a high-fat diet (HFD) through reinforcing intestinal barrier functions, regulating lipid metabolism, and improving inflammation. To clarify whether other mechanisms contribute to the anti-NAFLD efficacy of NF, the present study investigated the influence of NF on bile acid (BA) metabolism and gut microbiota in HFD-fed rats. The data demonstrated that NF changed the composition of colonic BA, particularly elevating conjugated BA and non-12OH BA levels. As shown by downregulated protein levels of FXR, FGF15, FGFR4, and ASBT and upregulated protein levels of CYP7A1 and CYP27A1, NF inhibited ileal FXR signaling, promoted BA synthesis, suppressed BA reabsorption, and facilitated fecal BA excretion. NF might affect hepatic FXR signaling, BA conjugation, and enterohepatic circulation by the changed mRNA levels of Fxr, Shp, Baat, Bacs, Bsep, Ntcp, Ibabp, and Ostα/ß. Meanwhile, NF regulated the gut microbiota, characterized by decreased BSH-producing genus, 7α-dehydroxylation genus, and increased taurine metabolism-related genus. Spearman rank correlation analysis implied that Colidextribacter, Adlercreutzia, Family_XIII_AD3011_group, Lachnospiraceae_UCG-010, Eisenbergiella, and UCG-005 were robustly associated with particular BA monomers. In conclusion, our experiment results suggested that NF could exert a mitigating effect on NAFLD via regulating BA metabolism and modulating the gut microbiota.

Numerical Analysis on Heat Characteristics of the Ventilation Basket for Fresh Tea Leaves.

Plastic baskets are commonly used as containers for fresh tea leaves during storage and transport after harvest. Nevertheless, there are significant challenges in controlling the core temperature of the basket since fresh tea leaves still maintain a certain degree of respiration after being harvested, with extremely high temperatures being the major factor for the color change of fresh tea leaves. A numerical model was developed to improve the temperature control of the plastic basket, by which the influence of different structural parameters on the core temperature in the plastic baskets with fresh tea leaves was analyzed. The accuracy of the model in predicting airflow and temperature distributions was validated against experimental data. The maximum RMSE was 1.158 °C and the maximum MRE was 5.410% between the simulated and test temperature value. The maximum deviation between the simulated velocity and test velocity was 0.11 m/s, the maximum RE was 29.05% and the maximum SD was 0.024. The results show that a plastic basket with a ventilation duct efficiently decreased the temperature of the fresh tea leaves and significantly affected the heat transfer between the fresh tea leaves and the ambient air compared to the plastic basket without a ventilation duct. Furthermore, the effect on the heat transfer was further expanded by the use of a plastic basket with a ventilation duct when the plastic baskets were stacked. The maximum temperature differences were 0.52 and 0.40 according to the stacked and single-layer products, respectively. The ambient temperature and the bulk density of the fresh tea leaves have a significant influence on the core temperature.