Context: There are insufficient data to support a link between serum albumin-to-globulin ratio (AGR) and mortality in individuals with diabetes. Objective: This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. Methods: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Hazard ratios (HR) and 95% CIs for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional-hazards models. Results: A total of 2415 all-cause deaths, including 688 CV deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (P-trend < .0001), cardiovascular mortality (P-trend < .001), and cancer mortality (P-trend < .01) were 0.51 (0.42-0.60), 0.62 (0.46-0.83), and 0.57 (0.39-0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per 1-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P < .001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. Conclusion: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those younger than 60 years and heavy drinkers.

Background Ovarian cancer poses a serious threat to women's health. Due to the difficulty of early detection, most patients are diagnosed with advanced-stage disease or peritoneal metastasis. We found that LncRNA MEG3 is a novel tumor suppressor, but its role in tumor occurrence and development is still unclear. Methods We investigated the expression level of MEG3 in pan-cancer through bioinformatics analysis, especially in gynecological tumors. Function assays were used to detect the effect of MEG3 on the malignant phenotype of ovarian cancer. RIP, RNA pull-down, MeRIP-qPCR, actinomycin D test were carried out to explore the m 6 A methylation-mediated regulation on MEG3. Luciferase reporter gene assay, PCR and Western blot were implemented to reveal the potential mechanism of MEG3. We further confirmed the influence of MEG3 on tumor growth in vivo by orthotopic xenograft models and IHC assay. Results In this study, we discovered that MEG3 was downregulated in various cancers, with the most apparent downregulation in ovarian cancer. MEG3 inhibited the proliferation, migration, and invasion of ovarian cancer cells. Overexpression of MEG3 suppressed the degradation of VASH1 by negatively regulating miR-885-5p, inhibiting the ovarian cancer malignant phenotype. Furthermore, we demonstrated that MEG3 was regulated at the posttranscriptional level. YTHDF2 facilitated MEG3 decay by recognizing METTL3‑mediated m 6 A modification. Compared with those injected with vector control cells, mice injected with MEG3 knockdown cells showed larger tumor volumes and faster growth rates. Conclusion We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.

BACKGROUND:Adolescents with temporomandibular joint (TMJ) anterior disk displacement (ADD) frequently develop dentofacial deformities. It is unknown whether adjunctive arthroscopic diskopexy compared with orthodontic treatment alone increases condylar growth and then improves dentofacial deformity. This study aimed to determine whether arthroscopic diskopexy before functional appliance (joint-occlusal treatment) or single functional appliance (occlusal treatment) increases condylar growth and improves dentofacial deformity among adolescents with TMJ ADD. METHODS:A multicenter, randomized, parallel, controlled trial was conducted in 3 centers in China. Adolescents diagnosed with TMJ ADD and dentofacial deformity were enrolled. Eligible participants were randomly assigned to a joint-occlusal group or occlusal group at a ratio of 2:1. Magnetic resonance imaging scans and cephalometric radiographs were evaluated at baseline, at 8 months, and at 14 months. The primary outcome was changes in condylar height from 14 months to baseline. Secondary outcomes were changes in skeletal position. RESULTS:A total of 240 patients (14.65 ± 1.88 years of age) were randomized (joint-occlusal group, 160; occlusal group, 80). The overall difference in condylar height between groups was 3.65 mm (95% CI, 3.10 to 4.19 mm; P < 0.001). The between-group differences in condylar height on the left and right sides were 3.60 mm (95% CI, 2.92 to 4.28 mm; P < 0.001) and 3.69 mm (95% CI, 3.06 to 4.32 mm; P < 0.001), respectively. Significant between-group differences were noted in skeletal position (all P < 0.001). CONCLUSION:Joint-occlusal treatment can promote condylar growth and improve dentofacial deformity in adolescents after 14 months when compared with single occlusal treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, I.

Background: Sepsis is a systemic inflammatory disease that can cause multiple organ damage. Circular RNAs (circRNAs) have been reported to play a regulatory role in sepsis-induced acute kidney injury (AKI); however, the role of circ_0114428 has not been studied. Methods: In this study, HK2 cells were treated with different concentrations of LPS to induce cell damage, and then the expressions of circ_0114428, microRNA-215-5p (miR-215-5p), and tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot examined the Bax and cleaved-Caspase-3 proteins. Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and thymidine analog 5-ethynyl-2 '-deoxyuridine (EdU) assay. In addition, cell apoptosis was detected by flow cytometry, and the levels of inflammatory factors were detected by enzyme-linked immunosorbent assay. Results: After LPS treatment with different concentrations, we found that LPS at 10 mu g/mL had the best effect on HK2 cells. Circ_0114428 was highly expressed in sepsis-AKI patients and LPS-treated HK2 cells. Knockdown of circ_0114428 restored the effects of LPS treatment on proliferation, apoptosis, and inflammatory response of HK2 cells. MiR-215-5p was a target of circ_0114428, and TRAF6 was a downstream target of miR-215-5p. Circ_0114428 regulated TRAF6 expression by sponging miR-215-5p in LPS-treated HK2 cells. Circ_0114428 regulated LPS-induced NF-kappa B signaling in HK2 cells by targeting miR-215-5p/TRAF6 axis. Conclusion: Circ_0114428 knockdown abolished the cell proliferation, apoptosis, and inflammatory damage in LPS-induced HK2 cells by targeting miR-215-5p/TRAF6/NF-kappa B.

Endometriosis is a multifactorial gynecological disease, with angiogenesis as a key hallmark. The role of exosomal microRNAs (miRNAs) in endometriosis is not well understood. This study investigates differentially expressed exosomal miRNAs linked to angiogenesis in endometriosis, clarifies their molecular mechanisms, and identifies potential targets. Primary endometrial stromal cells (ESCs) were cultured, and exosomes were extracted. In a co-culture system, ESC-derived exosomes were taken up by human umbilical vein endothelial cells (HUVECs). Endometriosis implant-ESC-derived exosomes (EI-EXOs) significantly promoted HUVEC proliferation, migration and tube formation compared to normal endometrium-exosomes (NE-EXOs), a finding consistent in vivo in mice. MiRNA sequencing and bioinformatics identified differentially expressed miR-21-5p from EI-EXOs, confirmed by RT-qPCR. The miR-21-5p inhibitor or GW4869 attenuated EI-EXO-induced HUVEC proliferation, migration, and tube formation. TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, which was reversed by adding EI-EXOs or upregulating miR-21-5p. These findings validate the crosstalk between ESCs and HUVECs mediated by exosomal miR-21-5p, and confirm the miR-21-5p-TIMP3 axis in promoting angiogenesis in endometriosis. KEY MESSAGES: ESC-derived exosomes were found to be taken up by recipient cells, i.e. HUVECs. Functionally, endometriosis implant-ESC-derived exosomes (EI-EXOs) could significantly promote the proliferation, migration and tube formation of HUVECs compared to normal endometrium-exosomes (NE-EXOs). Through miRNA sequencing and bioinformatics analysis, differentially expressed miR-21-5p released by EI-EXOs was chosen, as confirmed by qRT-PCR. miR-21-5p inhibitor or GW4869 was found to attenuate the proliferation, migration, and tube formation of HUVECs induced by EI-EXOs. In turn, TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, and this angiogenic phenotype was reversed once EI-EXOs were added or miR-21-5p was upregulated.

Introduction:Limb trauma (LT) encompasses a variety of conditions and currently poses certain therapeutic challenges in clinical practice.Aim:To assess the effectiveness of applying the vacuum sealing drainage (VSD) technique combined with carbon nanomaterial (CNM) dressings in the nursing treatment of LT patients.Material and methods:Eighty-six LT patients were enrolled into a control (Ctrl) group and an experimental (Exp) group. Patients in the Ctrl group underwent conventional wound cleansing and drainage methods with regular dressings, while those in the Exp group received VSD combined with CNM dressings. Both groups received the same nursing procedures. Various indicators were observed and compared to analyse the final outcomes.Results:The Exp group exhibited a higher favourable wound healing (FWH) rate, overall limb functional recovery (LFR) rate, and nursing satisfaction compared to the Ctrl group (p < 0.05). Meanwhile, patients in the Exp group experienced a greatly lower incidence of complications (IOC), pain scores, and average hospital stays (HS), presenting statistically/significant differences compared to those in the Ctrl group (p < 0.05). The combination of the VSD technique with CNM dressings demonstrated advantages in nursing treatment of LT patients. This approach could enhance rates of FWH, reduce IOC, alleviate postoperative pain, facilitate LFR, and shorten HS. Furthermore, patients in the Exp group expressed higher nursing satisfaction.Conclusions:Results of this work yielded a novel therapeutic option for clinical practice, enhancing treatment outcomes and rehabilitation processes for LT patients.

Transcatheter aortic valve implantation (TAVI) was originally devised as a treatment for patients with aortic stenosis (AS). It has since emerged as a beneficial alternative to surgical aortic valve replacement (SAVR), extending its reach to a broader array of patients. Our objective was to illustrate the developmental trends and focus areas in TAVI research. We sourced a total of 11,480 research papers on TAVI, published between 1994 and 2022, from the Web of Science Core Collection (WoSCC) database. We conducted a bibliometric analysis of these publications, generating cooperation maps, performing co-citation analysis of journals and references, and carrying out a cluster analysis of keywords. Our findings indicate that TAVI research grapples with numerous clinical challenges. We created knowledge maps that highlight contributing countries/institutions, authors, journals with high publication and citation rates, and notable references in this domain. North America and Europe have been at the forefront of research within the TAVI field. The institutions and authors from these regions exert significant influence in this area of study. Beginning in 2009, China has progressively expanded its research on TAVI over the past two decades. We anticipate that future research will increasingly focus on three key areas: implementation scope, lifelong management, outcomes and predicting the risk of TAVI. Research on TAVI is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future, especially for developing counties.

Cerebral protection devices (CPDs) often were applied to improve the safety of carotid artery stenting, but the CPD itself may cause fatal complications. We report a case of a retained CPD that was an Emboshield NAV6 device left in situ , which was retrieved successfully with esophageal biopsy forceps.

Electron spinning polarization has garnered increased attention for its potential to enhance device properties. However, its application in life health, specifically in anti-infection and tissue repair, remains under-explored. In this study, a ferromagnetic heterojunction CF (Fe3O4/TiO2) is constructed with spin-polarized electrons, demonstrating efficient antibiosis performance with ultrasound (US) assistance. The antibacterial mechanism is elucidated as follows: spin-polarized metallic states of Fe3O4 induce an asymmetric distribution in the electron spin state of TiO2, increasing the density of states of spin-polarized electrons near the Fermi level of CF. Under US treatment, the built-in electric field and spin-polarized electrons in CF synergistically suppress the recombination of sono-activated carriers, promoting reactive oxygen species (ROS) production. Simultaneously, the bacterial membrane is influenced by the micromagnetic field induced by spin-polarized electrons, causing a severe disturbance in the bacterial respiratory chain. The combined damage from ROS and disturbed respiratory chain results in bacterial death. Fortunately, the micromagnetic field built by CF activates specific mechanosensitive ion channels, including TREK1, Piezo1, and related pathways, enhancing osteoblast differentiation. Sonotherapy using CF exhibits an excellent therapeutic effect in treating osteomyelitis. This study provides novel insights into manipulating spin electrons for applications in life health. Magnetite Fe3O4 influences the electron spin states of TiO2, endowing the TiO2/Fe3O4 bioheterojunction with a heightened spin-polarization state and magnetic moment. The spin-polarized electrons in the bioheterojunction enhance sono-induced ROS production and disturb the bacterial respiratory chain, leading to bacterial death; they also form a micromagnetic field, activating mechanosensitive channels of osteoblasts, promoting osteogenesis differentiation and bone regeneration after antibiotic therapy. image

Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus-induced sepsis model is discovered, unexpectedly revealing a protective role for the host. Mechanistically, the protective effects are mediated by apoptotic macrophage-released apoEVs, which bound iron-containing proteins and neutralized α-toxin through interaction with membrane receptors (transferrin receptor and A disintegrin and metalloprotease 10). To further enhance therapeutic efficiency, apoEVs are engineered by incorporating mesoporous silica nanoparticles preloaded with anti-inflammatory agents (microRNA-146a). These engineered apoEVs can capture iron and neutralize α-toxin with their natural membrane while also regulating inflammation by releasing microRNA-146a in phagocytes. Moreover, to exploit the microcosmic movement and rotation capabilities, erythrocytes are utilized to drive the engineered apoEVs. The erythrocytes-driven engineered apoEVs demonstrate a high capacity for toxin and iron capture, ultimately providing protection against sepsis associated with high iron-loaded conditions. The findings establish a multifunctional agent that combines natural and engineered antibacterial strategies.

The aim of this study was to evaluate the clinical efficacy of alcohol-based therapy for patients with large odontogenic keratocysts (OKCs). The study was implemented as a retrospective, single-center study. Patients treated with ethanol-based therapy for odontogenic keratocyst were retrospectively evaluated for baseline and postoperative data. The pre- and postoperative clinical situation and the extent of radiographic shrinkage were compared. The event is defined as the achievement of >50% reduction in cyst volume. The cyst reduction rate calculated on panoramic radiographs ranged from 7.4% to 99.9% (mean [standard deviation] 55.3% [27.9%]) and was statistically significant (P < 0.05). Specifically, it has been found that, radiographically, 47.6% of patients achieved >50% reduction in cyst volume within 12 months. The continuous cortical bone was rebuilt, and the cyst cavity was filled with regenerated trabecular bone. The 22 included patients presented with nonclinical problems, had no need for further intervention, and exhibited persistent impaction of the teeth. The results of this study demonstrated that ethanol-based therapy triggered marked radiographic reductions of large OKC, indicating that using this technique is efficient.

Objective: Circular RNAs (circRNAs) are characterized as a class of covalently closed circRNA transcripts and are associated with various cellular processes and neurological diseases by sponging microRNAs. The most common feature of glaucoma, a form of retinal neuropathy, is the loss of retinal ganglion cells. Although the pathogenesis of glaucoma is not fully understood, elevated intraocular pressure is undoubtedly the only proven modifiable factor in the classic glaucoma model. This study investigated the role of circ_0023826 in glaucoma-induced retinal neurodegeneration by modifying the miR-188-3p/ mouse double minute 4 (MDM4) axis. Methods: The expression pattern of circ_0023826 was analyzed during retinal neurodegeneration. The effect of circ_0023826, miR-188-3p, and MDM4 on retinal neurodegeneration in vivo was assessed by visual behavioral testing and H&E staining in glaucoma rats, while that on in vitro retinal ganglion cells (RGCs) was evaluated by MTT assay, flow cytometry, Western blot, and ELISA. Bioinformatics analysis, RNA pull-down assay, luciferase reporter assay were performed to reveal the regulatory mechanism of circ_0023826-mediated retinal neurodegeneration. Results: Circ_0023826 expression was downregulated during retinal neurodegeneration. Upregulating circ_0023826 attenuated the visual impairment in rats and promoted the survival of RGCs in vitro. Circ_0023826 acted as a sponge of miR-188-3p sponge, resulting in increased expression of MDM4. MDM4 silencing or miR-188-3p upregulation reversed the protective effect of upregulated circ_0023826 on glaucoma-induced neuroretinal degeneration in vitro and in vivo. Conclusion: Overall, circ_0023826 protects against glaucoma by regulating the miR-188-3p/MDM4 axis, and targeted intervention of circ_0023826 expression is a promising therapeutic strategy for the treatment of retinal neurodegeneration.

Prostate cancer (PCa) is a serious threat to the health of men all over the world. The progression of PCa varies greatly among different individuals. In clinical practice, some patients often progress to advanced PCa. Therefore, accurate imaging for diagnosis and staging of PCa is particularly important for clinical management of patients. Conventional imaging examinations such as MRI and CT cannot accurately diagnose the pathological stages of advanced PCa, especially metastatic lymph node (LN) stages. As a result, developing an accurate molecular targeted diagnosis is crucial for advanced PCa. Prostate specific membrane antigen (PSMA) is of great value in the diagnosis of PCa because of its specific expression in PCa. At present, researchers have developed positron emission tomography (PET) targeting PSMA. A large number of studies have confirmed that it not only has a higher tumor detection rate, but also has a higher diagnostic efficacy in the pathological stage of advanced PCa compared with traditional imaging methods. This review summarizes recent studies on PSMA targeted PET in PCa diagnosis, analyzes its value in PCa diagnosis in detail, and provides new ideas for urological clinicians in PCa diagnosis and clinical management.

Background:The co-existence of Sjögren's syndrome and aortic stenosis (AS) is infrequent, and there lack cases of transcatheter aortic valve replacement (TAVR) for these patients with detailed management decision-making.Case summary:We report a case of a female patient who had AS and Sjögren's syndrome with leukopaenia and thrombocytopaenia. To overcome co-existing hyper-coagulation and high thrombogenesis risk, difficult lifetime valve management, and high infection risk, we performed TAVR with 3D printing and formulated antithrombotic and antibiotic schemes.Conclusion:This case provided a successful experience of TAVR in patients with Sjögren's syndrome. Long-term follow-up will be conducted, and optimization of the therapeutic regimen requires further exploration.

The function of Vasohibin-1 (VASH1) in human cancer has not been thoroughly or comprehensively examined. Here, we identified the tumor suppressor part of VASH1 across cancers, including epithelial ovarian tumors. Our study carefully contrasted the expression of VASH1 in pancancer and nontumorous tissues in a public database to explore its regulatory role in clinical prognosis, diagnosis, tumor purity, and immune cell infiltration. Next, we explored the antitumor mechanism of VASH1 through drug sensitivity, functional enrichment, and phenotypic experiments in ovarian cancer. Research suggests that the expression of VASH1 in neoplastic tissues is lower than that in normal tissues. VASH1 affects the OS and RFS of several tumor types. In addition, VASH1 expression resulted in a high OS and RFS in the diagnosis of tumor and nontumor tissues and negatively regulated tumor purity. Moreover, VASH1 controls the tumor microenvironment by regulating immunocyte infiltration. In ovarian cancer, VASH1 can serve as a biomarker to estimate the efficacy of chemotherapy. Functional enrichment analysis suggests that VASH1 plays a tumor suppressor role by regulating the extracellular matrix receptor pathway. VASH1 inhibition of the malignant phenotype of ovarian cancer cells was further confirmed by in vivo experiments. These results indicate that VASH1 acts as a cancer-inhibiting factor and potential therapeutic target in ovarian cancer.

BackgroundExcessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China.Methods42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1st June 2006. All participants were followed-up, biennially, until 31st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups.ResultsAt a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at ≥65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup.ConclusionParticipants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight.

Background: Clear cell renal cell carcinoma is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune cell infiltration and biological function in ccRCC are still poorly understood.Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed using multiple databases, including TCGA, GEO, TIMER, and UALCAN Kaplan–Meier survival analysis, gene set enrichment analysis gene ontology enrichment Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using TCGA-KIRC profiles. Protein‒protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by immunohistochemistry using a ccRCC tissue chip. Finally, MTT assays, colony-formation assays, cell flow cytometry analyses, EdU-staining assays, wound-healing assays, and transwell migration and invasion assays were conducted to assess the biological function of GTSE1 in vitro.Results: GTSE1 was overexpressed in ccRCC tissues and cells, and GTSE1 overexpression was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its coexpressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction, such as T-cell activation and innate immune response, through multiple signaling pathways, including the P53 signaling pathway and T-cell receptor signaling pathway. Furthermore, we observed a significant relationship between GTSE1 expression and the levels of infiltrating immune cells in ccRCC. Biological functional studies demonstrated that GTSE1 could promote the malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, and invasion capacity and decreasing the sensitivity of ccRCC cells to cisplatin.Conclusion: Our results indicate that GTSE1, serving as a potential oncogene, can promote malignant progression and cisplatin resistance in ccRCC. Additionally, high GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.

BackgroundThe correlation between dietary vitamin B1 intake and cardiovascular diseases, as well as the all-cause and cardiovascular-associated mortality, is not well known. A large-scale data pool was used to examine the aforementioned correlations of Vitamin B1.MethodsThis paper analyzed the dietary data from the survey conducted by National Health and Nutrition Examination (NHANES; 1999–2018). The correlation of vitamin B1 intake in each quartile with cardiovascular diseases such as hypertension, coronary heart disease, myocardial infarction and heart failure was analyzed using multivariate logistic regression models. The hazard ratios for dietary vitamin B1 intake in each quartile, along with all-cause and cardiovascular-associated mortality, were performed using multivariate cox regression analysis, setting the lowest quartile (Q1) as a reference. The restricted cubic spline (RCS) method was used to study the nonlinear relationship. Subgroup stratification and sensitivity analyses were used to further investigate the association between them.ResultsThe study enrolled 27,958 subjects (with a mean follow-up time of 9.11 years). After multivariate adjustment, dietary vitamin B1 intake was significantly associated with hypertension, heart failure and cardiovascular mortality, with the most significant association in quartile 4 (Q4) of vitamin B1 intake. The results of the restricted cubic spline showed that vitamin B1 intake was nonlinearly associated with hypertension, whereas it was linearly associated with heart failure and cardiovascular mortality. Meanwhile, a dose–response correlation was observed, indicating that increased vitamin B1 intake leads to reduced risk of both cardiovascular prevalence and mortality. The stratified analysis showed that the correlation between age ≥ 50 years, overweight, smoking history, drinking history and dyslipidemia were more significant in male patients. The associations remained similar in the sensitivity analyses.ConclusionThe large NHANES-based studies indicate a gradual trend toward decreasing the risk of hypertension and heart failure prevalence and cardiovascular mortality with increasing dietary vitamin B1 intake. This association is especially significant in elderly-aged men, overweight individuals, smokers, drinkers, and dyslipidemia patients.

Recent studies have shown the pathogenesis of acute lung injury (ALI) involves circular RNA (circRNA). However, there are no data on the role of circSLCO3A1 in ALI and the underlying mechanism. ALI-like cell injury was induced by stimulating human pulmonary alveolar epithelial cells (HPAEpiCs) using lipopolysaccharide (LPS). The expression of circSLCO3A1, miR-424-5p and high mobility group box 3 (HMGB3) was detected by quantitative real-time polymerase chain reaction. Cell viability and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Enzyme-linked immunosorbent assay was performed to determine the production of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein 1 (MCP-1). Caspase-3 activity was detected by caspase-3 activity assay. Protein expression of inducible NOS (iNOS), cyclooxygenase-2 (COX2), p-p65 and p65 was analyzed by Western blot. The interactions among circSLCO3A1, miR-424-5p and HMGB3 were identified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. CircSLCO3A1 and HMGB3 expression were significantly increased, while miR-424-5p was decreased in LPS-treated HPAEpiCs and the serum of septic ALI patients in comparison with controls. CircSLCO3A1 knockdown assuaged LPS-induced HPAEpiC inflammation and apoptosis. Besides, circSLCO3A1 targeted miR-424-5p and regulated LPS-triggered HPAEpiC inflammation and apoptosis by binding to miR-424-5p. Under the treatment of LPS, miR-424-5p mediated HPAEpiC disorders by targeting HMGB3. Importantly, circSLCO3A1 modulated HMGB3 production by interacting with miR-424-5p. CircSLCO3A1 absence assuaged LPS-induced HPAEpiC inflammation and apoptosis through the miR-424-5p/HMGB3 axis.

The homing rate of transplanted mesenchymal stem cells (BMSCs) after acute myocardial infarction (AMI) is generally low, with only 0%-6% of the number of transplanted stem cells distributed to the heart; therefore, this study will investigate the therapeutic effects and mechanisms of miR-183-5p-modified BMSCs cells on myocardial ischemia and hypoxia caused by AMI. In this experiment, After first establishing the BMSCs ischemic-hypoxic injury model, the rats were divided into healthy group, model group, BMSCs group and BMSCs+ miR-183-5P group, where the healthy group was taken to normal culture, the model group caused myocardial ischemic-hypoxic damage, the BMSCs group underwent BMSCs stem cell transplantation on the basis of the model group, and the BMSCs+ miR-183-5P group was group was cultured with BMSCs-derived miR-183-5P on the basis of the model group. Myocardial tissue sections of rats in each group were taken for HE staining and histopathological changes were observed by light microscopy. The proliferation, apoptosis and migration ability of the cells were detected by CCK-8 method, flow cytometry and Transwell transfer method. The target gene of miR-183-5P was predicted using bioinformatics software, and the binding of miR-183-5P to FOXO1 was investigated. The expression of FOXO1 was analysed using qRT-PCR and protein blotting techniques. The qRT-PCR results showed that the expression of miR-183-5P was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The value-added ability and the migration capacity of BMSCs in the BMSCs group and BMSCs+ miR-183-5P group were increased compared with the model group, and the BMSCs+ miR-183-5P group BMSCs had the highest proliferation capacity and the migration capacity(P<0.05). In contrast, the apoptotic capacity of BMSCs was significantly reduced in the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the apoptotic capacity of BMSCs was lowest in the BMSCs+ miR-183-5P group (P<0.05). The bioinformatics software RegRNA 2. 0 was used to predict that the specific target gene that may be regulated by miR-183-5P is FOXO1 and confirmed that miR-183-5P does indeed have a targeting relationship with the FOXO1 pathway. After upregulation of miR-183-5P expression, the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, and the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). The Western blotting showed that the expression of FOXO1 mRNA was higher in BMSCs of the BMSCs group and BMSCs+ miR-183-5P group compared with the model group, especially the expression was highest in the BMSCs+ miR-183-5P group (P<0.05). In conclusion, BMSCs-derived miR-183-5P can target and regulate FOXO1 to increase the proliferation and migration of BMSCs and reduce their apoptosis, and can also reduce myocardial tissue edema and inflammatory response by increasing the expression of FOXO1 mRNA, which can increase the survival rate of BMSCs and provide a clinical basis for BMSCs transplantation.