Reliability and validity of simple Chinese version of grit scale for elementary school students.

BACKGROUND: The Grit scale (GS-12) is a widely used rating scale that assess passion and perseverance. The present study aimed to evaluate the reliability and validity of simple Chinese Version of Grit Scale (GS-SC) among Chinese adolescents. METHODS: Seven hundred one primary school students were recruited as Sample 1. Item analysis and exploratory factor analysis (EFA) were conducted on Sample 1 to preliminarily examine the structure of the scale. Sample 2 consisted of 5,384 primary school students. Confirmatory factor analysis (CFA) and verification of reliability and validity were conducted on Sample 2 to establish a formal scale and further verify the psychometric properties by applying item response theory (IRT). RESULTS: EFA and CFA revealed a clear two-factor structure. The results demonstrated that the Simplified Chinese Version of Grit Scale had adequate internal consistency and re-test reliability. GS-CS also showed good criterion-validity with personality, self-control, effort regulation and academic achievement. Furthermore, all the items show a acceptable fit to the GRM and have good discrimination (ranging from 2.13 to 3.45) and moderate difficulty(ranging from-1.58 to 0.95). CONCLUSIONS: The reliability and validity of the GS-SC are good, indicating that the scale can be used as an effective tool for measuring the grit of primary school students in China.

Music therapy for tinnitus: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of music therapy in the treatment of tinnitus. METHODS: Three English databases (PUBMED, Embase, Web of Science) and three Chinese databases (CNKI, VIP, and Wanfang) were searched, and eligible articles were selected according to the set inclusion criteria. Clinical efficacy was used as the primary outcome, and each score was used as the secondary outcome. Using RevMan5.3 software for statistical analysis. RESULTS: A total of 14 studies involving 1239 tinnitus patients were included. The results of the meta-analysis showed that music therapy had a certain clinical efficacy in the treatment of tinnitus, but there was no significant difference compared with the control group (OR = 1.00, 95%CI =0.83-1.22; P = 1.00). However, music therapy significantly improved THI score (MD = -6.77, 95 % CI = -9.62 to -3.92; P < 0.00001), TSQ (MD = -2.80, 95 % CI = -3.23 to -2.36; P < 0.00001), tinnitus loudness (MD = -3.90, 95 % CI = -6.58 to -1.23; P = 0.004), VAS score (MD = -1.11, 95 % CI = -2.11 to -0.11; P = 0.03) and TQ score (MD = -8.36, 95 % CI = -11.10 to -5.62; P < 0.001). CONCLUSION: Music therapy is an effective method for the treatment of tinnitus, which can improve the THI score, tinnitus severity, VAS score, and TQ score and reduce the loudness of tinnitus. Due to the low quality of the included literature, the current conclusions need to be further verified by more and higher-quality studies.

Spinal microglial M1 polarization contributes paclitaxel-induced neuropathic pain by triggering cells necroptosis.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

Hydrochemistry dynamics in a glacierized headwater catchment of Lhasa River, Tibetan Plateau.

Mountain glaciers are essential for supplying water resources that sustain downstream communities and livelihoods, yet the hydrogeochemical dynamics at glacier terminals and the impact of glacier retreat on downstream water chemistry are not fully understood. This study addresses this by conducting comprehensive observations and analysis of water chemistry at refined spatial and temporal resolutions in the Lhasa River Valley Glacier No. 1 (LRVG-1) catchment, a vital source of drinking and irrigation water for the local population on the Tibetan Plateau. Our findings reveal a weakly alkaline water environment within this glacierized basin, with HCO3- and Ca2+ as the dominant anions and cations, respectively, resulting in a hydrochemical pattern classified as HCO3--Ca2+ type. Solute concentrations increase along the glacier meltwater pathway, influenced by water-rock interaction, dilution, and diverse sources. The cations are predominantly from carbonate weathering, constituting 72.86 % of the total cations, followed by sulfide oxidation (11.08 %), glacier meltwater inputs (8.13 %), and silicate weathering (7.93 %). The contribution of cations from glacier meltwater diminishes as they travel along the glacier meltwater flow pathway. Our study indicates the localized yet significant impact of glacier meltwater on hydrochemistry, particularly in the vicinity of the glacier terminus. We recommend considering glacial meltwater and the entire glacier watershed as a continuum, essential for understanding the cumulative effects of glacier melt and human activities on water quality. This perspective is crucial for predicting future river chemistry trajectories in high-mountain basins and informing policy-making for water quality conservation across the Tibetan Plateau.

Analysis of the effectiveness of PDT with 5-aminolevulinic acid in comparison to blue/red light combined with intralesional triamcinolone injection in treatment of severe inflammatory acne: A retrospective study.

OBJECTIVE: In this study, the therapeutic effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in comparison to blue/red light combined with intralesional triamcinolone injection for severe inflammatory acne was evaluated and analyzed. METHODS: One hundred and four cases of severe inflammatory acne were analyzed in this study. They were divided into two groups as control and observation groups, 52 cases in each group. The control group (group A) received red and blue light combined with triamcinolone injection and lidocaine injection (1:4), while the observation group (Group B) was treated with ALA-PDT. Finally, the therapeutic effect and the occurrence of adverse reactions were compared between the two groups. RESULTS: After 2, 4 and 6 weeks, the effectiveness rates of group B was 28.85%, 75.00%, and 86.54%, respectively while it was 9.62%, 51.92%, and 69.23%, respectively in group A. The difference between A and B was statistically remarkable (χ2 = 6.1905, 5.9713, 4.5217, p = 0.0128, 0.0145, 0.0335 at p < 0.05). In addition, the incidence of adverse reactions in B was 5.77%, lower than A (32.69%). This difference between A and B was statistically remarkable (χ2 = 12.1333, p = 0.0005). After 2, 4, and 6 weeks of treatment, the number of residual lesions in the group B group was remarkably lower than group A (p < 0.01). There was remarkable difference in the incidence of pain, burning sensation, pigmentation and erythema between the two groups. CONCLUSIONS: The therapeutic effect of ALA-PDT in the treatment of severe acne is better than red blue light combined with triamcinolone injection and lidocaine injection. In addition, ALA-PDT has an ideal effect in the treatment of severe acne.

WITHDRAWN: Analysis of the Efficacy of Drilling Decompression Autologous Bone Marrow and Allogeneic Bone Grafting in the Treatment of HIV-positive Patients with Early Osteonecrosis of the Femoral Head

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Tissue adhesive indocyanine green-locking granular gel-mediated photothermal therapy combined with checkpoint inhibitor for preventing postsurgical recurrence and metastasis of colorectal cancer.

Developing effective therapy to inhibit postoperative recurrence and metastasis of colorectal cancer (CRC) is challenging and significant to reduce mortality and morbidity. Here, a granular hydrogel, assembled from gelatin microgels by dialdehyde starch and interpenetrated with in situ polymerized poly(sulfobetaine methacrylate-co-N-isopropylacrylamide) (P(SBMA-co-NIPAM)), is prepared to load and lock Food and Drug Administration (FDA)-approved indocyanine green (ICG) with definite photothermal function and biosafety for photothermal therapy (PTT) combining with checkpoint inhibitor. The presence of P(SBMA-co-NIPAM) endows granular hydrogel with high retention to water-soluble ICG, preventing easy diffusion and rapid scavenging of ICG. The ICG-locking granular hydrogel can be spread and adhered onto the surgery site at wet state in vivo, exerting a persistent and stable PTT effect. Combined with αPD-L1 treatment, ICG-locking granular hydrogel-mediated PTT can eradicate postsurgery residual and metastatic tumors, and prevent long-term tumor recurrence. Further mechanistic studies indicate that combination treatment effectively promotes dendritic cells maturation in lymph nodes, enhances the number and infiltration of CD8+ T and CD4+ T cells in tumor tissue, and improves memory T cell number in spleen, thus activating the antitumor immune response. Overall, ICG-locking gel-mediated PTT is expected to exhibit broad clinical applications in postoperative treatment of cancers, like CRC.

Construction of type-II scheme SnO@HfC photocatalyst for bisphenol A degradation via peroxymonosulfate activation; DFT and self-cleaning analysis.

In this study, novel stannous oxide@hafnium carbide (SnO@HfC) nanocomposite was successfully manufactured by an appropriate hydrothermal scheme which was utilized for the photocatalytic degradation of BPA by stimulation of peroxymonosulfate (PMS) and self-cleaning application. Numerous methods were applied for the characterization of photocatalyst and demonstrated the successful preparation of SnO@HfC nanocomposite. The crystal structures, band structures and density of states for SnO and HfC were explored by DFT analysis. The amazing PMS stimulation performance of SnO@HfC nanocomposite originated from the establishment of a heterojunction, which led to the enhancement of the light response aptitude and the electron conduction competence of the composite. BPA was degraded by 0.75 g/L PMS and SnO@HfC at neutral pH during the period of 60 min. In order to identify active groups in the reaction procedure, quenching experiments and electron paramagnetic resonance (EPR) approaches were also used. In the subsequent active species scavenging assays, where sulfate radicals, hydroxyl radicals, holes, and superoxide radicals were engaged in the degradation of BPA. While, liquid phase mass spectrometry (LC-MS) was used to pinpoint the intermediate metabolites in the course of degradation. SnO@HfC/PMS/light system delivered excellent TOC removal efficiency and less ions leaching. The SnO@HfC nanocomposite proved good durability and reusability in continuous cycle tests along with excellent self-cleaning function on the glass substrate. The SnO@HfC nanocomposite performs admirably in terms of self-cleaning application. The SnO@HfC nanocomposite is expected to be used in the future for the treatment of wastewater that contains pharmaceuticals due to its superior stability and reusability after five consecutive cycles.

Transcriptome analysis of response mechanism to Microcystin-LR and microplastics stress in Asian clam (Corbicula fluminea).

In this study, we analyzed the hepatopancreas tissues of Asian Clam (Corbicula fluminea) exposed to three different adverse environmental conditions from the same batch using RNA-seq. The four treatment groups included the Asian Clam group treated with Microcystin-LR (MC), the Microplastics-treated group (MP), the Microcystin-LR and Microplastics-treated group (MP-MC), and the Control group. Our Gene Ontology analysis revealed 19,173 enriched genes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified 345 related pathways. The KEGG pathway analysis demonstrated that the MC vs control group and the MP vs control group were significantly enriched in immune and catabolic pathways such as Antigen processing and presentation, Rheumatoid arthritis, Lysosome pathway, Phagosome pathway, and Autophagy pathway. We also evaluated the effects of Microplastics and Microcystin-LR on the activities of eight antioxidant enzymes and immune enzymes in Asian clams. Our study enriched the genetic resources of Asian clams and provided valuable information for understanding the response mechanism of Asian clams to microplastics and microcystin in the environment, through the identification of differentially expressed genes and related pathway analyses from the large number of transcriptome sequences obtained.

Myelodysplastic Syndrome Treated by Integrated Chinese and Western Medicine: A Case Report.

Context: Myelodysplastic syndrome (MDS) is a group of highly heterogeneous, malignant clonal diseases derived from hematopoietic stem cells. PD-1 monoclonal antibodies can have a synergistic effect with hypomethylating agents (HMAs), especially for patients with drug resistance to demethylation drugs. TCM in the treatment of MDS can improve hematological indexes, and for some patients, control the proliferation of primitive cells and delay or even block the transformation to leukemia. Objective: The study intended to examine the therapeutic effects of programmed cell death-1 (PD-1) inhibitors and azacitidine combined with the Yisuifang Thick Decoction in the treatment of MDS with older, high-risk patients. Design: The research team performed five prospective case studies. Setting: The study took place at the East Hospital affiliated with Beijing University of Chinese Medicine in Beijing, China. Participants: Participants were five older, high-risk MDS patients at the hospital who received PD-1 and azacitidine combined with Yisuifang Thick Decoction between April 2020 and June 2021. Outcome Measures: The research team measured: (1) treatment duration, (2) curative effects, (3) myelosuppression, (4) immune-related adverse reactions, (5) ending outcomes, and (6) progression-free survival (PFS). Results: The male to female ratio for the five participants was 3:2, and the median age was 69 years, with a range from 62 to 79 years. Four participants had refractory HR-MDS and one had primary MDS. The median treatment duration was 3 months, with a range from 2 to 4 months, and the median progression-free survival (PFS) was 5 months, with a range from 3 to 14 months. All participants achieved a partial response (PR) or a complete remission with incomplete count recovery (CRi) and showed improvement in serological indexes. Conclusions: Older, high-risk MDS patients generally have poor physical conditions, often accompanied by a poor karyotype prognosis and a poor prognosis for survival. Therefore, the combination of PD-1, azacytidine, and Yisuifang Thick Decoction may be an effective way to treat HR-MDS.

Preparation and Properties of Natural Polysaccharide-Based Drug Delivery Nanoparticles.

In recent years, natural polysaccharides have been widely used in the preparation of drug delivery systems. In this paper, novel polysaccharide-based nanoparticles were prepared by layer-by-layer assembly technology using silica as a template. The layers of nanoparticles were constructed based on the electrostatic interaction between a new pectin named NPGP and chitosan (CS). The targeting ability of nanoparticles was formed by grafting the RGD peptide, a tri-peptide motif containing arginine, glycine, and aspartic acid with high affinity to integrin receptors. The layer-by-layer assembly nanoparticles (RGD-(NPGP/CS)3NPGP) exhibited a high encapsulation efficiency (83.23 ± 6.12%), loading capacity (76.51 ± 1.24%), and pH-sensitive release property for doxorubicin. The RGD-(NPGP/CS)3NPGP nanoparticles showed better targeting to HCT-116 cells, the integrin αvß3 high expression human colonic epithelial tumor cell line with higher uptake efficiency than MCF7 cells, the human breast carcinoma cell line with normal integrin expression. In vitro antitumor activity tests showed that the doxorubicin-loaded nanoparticles could effectively inhibit the proliferation of the HCT-116 cells. In conclusion, RGD-(NPGP/CS)3NPGP nanoparticles have potential as novel anticancer drug carriers because of their good targeting and drug-carrying activity.

Enhanced Production of Active Photosynthetic and Biochemical Molecules in Silybum marianum L. Using Biotic and Abiotic Elicitors in Hydroponic Culture.

Elicitors are stressors that activate secondary pathways that lead to the increased production of bioactive molecules in plants. Different elicitors including the fungus Aspergillus niger (0.2 g/L), methyl jasmonate (MeJA, 100 µM/L), and silver nanoparticles (1 µg/L) were added, individually and in combination, in a hydroponic medium. The application of these elicitors in hydroponic culture significantly increased the concentration of photosynthetic pigments and total phenolic contents. The treatment with MeJA (methyl jasmonate) (100 µM/L) and the co-treatment of MeJA and AgNPs (silver nanoparticles) (100 µM/L + 1 µg/L) exhibited the highest chlorophyll a (29 µg g-1 FW) and chlorophyll b (33.6 µg g-1 FW) contents, respectively. The elicitor MeJA (100 µM/L) gave a substantial rise in chlorophyll a and b and total chlorophyll contents. Likewise, a significant rise in carotenoid contents (9 µg/g FW) was also observed when subjected to meJA (100 µM/L). For the phenolic content, the treatment with meJA (100 µM/L) proved to be very effective. Nevertheless, the highest production (431 µg/g FW) was observed when treated with AgNPs (1 µg/L). The treatments with various elicitors in this study had a significant effect on flavonoid and lignin content. The highest concentration of flavonoids and lignin was observed when MeJA (100 mM) was used as an elicitor, following a 72-h treatment period. Hence, for different plant metabolites, the treatment with meJA (100 µM/L) and a co-treatment of MeJA and AgNPs (100 µM/L + 1 µg/L) under prolonged exposure times of 120-144 h proved to be the most promising in the accretion of valuable bioactive molecules. The study opens new insights into the use of these elicitors, individually or in combination, by using different concentrations and compositions.

Sustained release silicon from 3D bioprinting scaffold using silk/gelatin inks to promote osteogenesis.

Repairing extensive bone defects that cannot self-heal has been a clinical challenge. The construction of scaffolds with osteogenic activity through tissue engineering can provide an effective strategy for bone regeneration. This study utilized gelatin, silk fibroin, and Si3N4 as scaffold materials to prepare silicon-functionalized biomacromolecules composite scaffolds using three-dimensional printing (3DP) technology. This system delivered positive outcomes when Si3N4 levels were 1 % (1SNS). The results showed that the scaffold had a porous reticular structure with a pore size of 600-700 µm. The Si3N4 nanoparticles were distributed uniformly in the scaffold. The scaffold could release Si ions for up to 28 days. In vitro experiments showed that the scaffold had good cytocompatibility, promoting the osteogenic differentiation of mesenchymal stem cells (MSCs). In vivo experiments on bone defects in rats showed that the 1SNS group facilitated bone regeneration. Therefore, the composite scaffold system showed potential for application in bone tissue engineering.

Motivation, self-efficacy, perception, curiosity, and barriers toward medical research among undergraduates in China.

Medical research is important to scientific progress and medical education. Institutions worldwide have sought to increase student involvement in research such as clinician-scientists training programs, while little is known about how medical undergraduates perceive research. A cross-sectional study was conducted in Chongqing Medical University, Chongqing, China, with first-fourth year undergraduates. An online, anonymous, and self-rating 5-point Likert questionnaire was conducted to investigate medical undergraduates' demographic characteristics and assess motivation, self-efficacy, perception, curiosity, and barriers regarding medical research. Content validity was checked with experts and face validity was checked for clarity and understanding of the questionnaire. The Cronbach's alpha coefficient of the questions ranged from 0.813 to 0.879. A total of 3273 medical undergraduates were surveyed, and 86.62% (2835) participants (male 962, female 1873) were identified as effective. Males scored higher than females on self-efficacy (p < 0.001), perception (p = 0.017), and curiosity (p < 0.001), and lower on barriers (p < 0.001). The second year students are at the peak of their perception (p = 0.006) and lowest barrier scores (p = 0.003). Students with scientific research experience scored higher in motivation (p = 0.002), self-efficacy (p < 0.001), perception (p < 0.001), and curiosity (p < 0.001). Lack of proper mentoring opportunity (86.2%) and knowledge (84.5%) were the main barriers in conducting research. Even though they have a positive perspective, only a few undergraduates enrolled in research. Medical universities should encourage faculties to supervise and guide undergraduates' projects, and provide feasible solutions for students to learn scientific knowledge and skills. It is vital to build a research-oriented environment and academic atmosphere.

Epidemiololgical and etiological analysis of two clusters of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which is primarily transmitted via tick bites. Clusters of SFTS caused by human-to-human transmission have been reported both at home and abroad, mainly focused on the transmission or exposure modes. However, the correlation between SFTS clusters and viral genotypes has not been investigated. This study mainly reported two clusters of SFTS in Xinyang City, Henan Province, from 2022 to 2023, discussed the possible route of person-to-person transmission of SFTSV infection and analyzed the association between SFTS clusters and virus genotypes. We found that two groups of SFTSV in two clusters were clustered separately into different genotypes through viral sequence analysis of 4 confirmed patients. We also performed phylogenetic analysis, after including SFTSV sequences obtained from SFTS clusters deposited in the GenBank. Three SFTSV genotypes have been reported among cases of human-to-human transmission, suggesting that the occurrence of SFTS clusters may not be related to SFTSV genotypes. This study provided genetic evidence for revealing the chain of human-to-human transmission of SFTS clusters, indicating that contact with patients' blood is an important transmission route of SFTSV. The findings laid the foundation for preventing and controlling human-to-human transmission of SFTS.

S-propargyl-cysteine promotes the stability of atherosclerotic plaque via maintaining vascular muscle contractile phenotype.

Introduction: Plaque rupture in atherosclerosis contributes to various acute cardiovascular events. As a new sulfide-containing donor, S-propargyl-cysteine (SPRC) has been reported to play a beneficial role in cardioprotection, potentially through its anti-inflammatory, anti-oxidative and anti-atherogenic activities. Our previous study observed an increase in eNOS phosphorylation in endothelial cells. However, it remains unclear whether SPRC influences vascular smooth muscle cells (VSMCs) within the plaque and if this effect contributes to plaque stabilization. Methods: An atherosclerotic unstable plaque mouse model was established by subjecting ApoE-/- mice to tandem stenosis of the right carotid artery along with a Western diet. Daily SPRC administration was conducted for 13 weeks. Plaque morphology and stability were assessed using MRI scanning and histopathological staining. In our in vitro studies, we stimulated human artery vascular smooth muscle cells (HAVSMCs) with platelet-derived growth factor-BB (PDGF-BB), both with and without 100 µM SPRC treatment. Cell phenotype was assessed using both Western blot and Real-time PCR. Cell proliferation was assessed using the BrdU cell proliferation kit and immunofluorescence of Ki-67, while cell migration was measured using scratch wound healing and transwell assay. MiR-143-3p overexpression and knockdown experiments were used to investigate whether it mediates the effect of SPRC on VSMC phenotype. Results and Discussion: SPRC treatment reduced plasma lipid levels, increased collagen content and decreased cell apoptosis in atherosclerotic plaques, indicating improved plaque stability. Both in vivo and in vitro studies elucidated the role of SPRC in preserving the contractile phenotype of VSMCs through up-regulation of miR-143-3p expression. Furthermore, SPRC suppressed the pro-proliferation and pro-migration effects of PDGF-BB on HAVSMCs. Overall, these findings suggest that the inhibitory effect of SPRC on phenotype switch from contractile to synthetic VSMCs may contribute to its beneficial role in enhancing plaque stability.

miR194 hypomethylation regulates coronary artery disease pathogenesis.

Coronary artery disease (CAD) is one of the most common heart diseases, characterized by the hardening and narrowing of arteries, resisting blood supply to cardiac muscle. Despite extensive research, the pathogenesis and therapeutic options for CAD remain limited. Epigenetic regulation plays a critical role in CAD progression. Here, we report a unique DNA methylation-miRNA-mRNA regulatory network for CAD, delineated through DNA methylation assays, miRNA and mRNA sequencing, bioinformatics analyses. We also identified key signaling pathways in this network, including the miR194 promoter-miR194-MAPK signaling pathway by pyrosequencing, methylation PCR, qRT-PCR. This pathway could play a role in CAD by apoptosis. Our findings suggested that this signaling pathway may be a potential therapeutic target for CAD. We believe that our study significantly contributes to an improved understanding of the role of specific miRNAs methylation, miRNA, and mRNAs in CAD pathogenesis.

A nomogram for predicting the risk of mortality in patients with acute pancreatitis and Gram-negative bacilli infection.

Objective: Gram-negative bacilli (GNB) are common pathogens of infection in severe acute pancreatitis (SAP), and their occurrence increases the mortality of SAP. Early identification of SAP severity and prognosis is of great significance to SAP treatment. This study explored risk factors for mortality in patients with SAP and GNB infection and established a model for early prediction of the risk of death in GNB-infected SAP patients. Methods: Patients diagnosed with SAP from January 1, 2016, to March 31, 2022, were included, and their baseline clinical characteristics were collected. Univariate logistic regression analysis was performed to screen for death related variables, and concurrently, a Boruta analysis was performed to identify potentially important clinical features associated with mortality. The intersection of the two results was taken for further multivariate logistic regression analysis. A logistic regression model was constructed according to the independent risk factor of death and then visualized with a nomogram. The performance of the model was further validated in the training and validation cohort. Results: A total of 151 patients with SAP developed GNB infections. Univariate logistic regression analysis identified 11 variables associated with mortality. The Boruta analysis identified 11 clinical features, and 4 out of 9 clinical variables: platelet counts (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.99-1.00; p = 0.007), hemoglobin (OR 0.96, 95% CI 0.92-1; p = 0.037), septic shock (OR 6.33, 95% CI 1.12-43.47; p = 0.044), and carbapenem resistance (OR 7.99, 95% CI 1.66-52.37; p = 0.016), shared by both analyses were further selected as independent risk factors by multivariate logistic regression analysis. A nomogram was used to visualize the model. The model demonstrated good performance in both training and validation cohorts with recognition sensitivity and specificity of 96% and 80% in the training cohort and 92.8% and 75% in the validation cohort, respectively. Conclusion: The nomogram can accurately predict the mortality risk of patients with SAP and GNB infection. The clinical application of this model allows early identification of the severity and prognosis for patients with SAP and GNB infection and identification of patients requiring urgent management thus allowing rationalization of treatment options and improvements in clinical outcomes.

An Inducible Nitric Oxide Synthase Dimerization Inhibitor Prevents the Progression of Osteoarthritis.

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments. Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 µM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1ß-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry. Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1ß-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage. Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug.