Investigation of morphology and structure of drug-loaded PLA-b-PEO-b-PLA polymeric micelle: A dissipative particle dynamics simulations study.

The dissipative particle dynamics (DPD) simulation was used to study the morphologies and structures of the paclitaxel-loaded PLA-b-PEO-b-PLA polymeric micelle. We focused on the influences of PLA block length, PLA-b-PEO-b-PLA copolymer concentration, paclitaxel drug content on morphologies and structures of the micelle. Our simulations show that: (i) with the PLA block length increase, the self-assemble structure of PLA-b-PEO-b-PLA copolymers with paclitaxel vary between onion-like structure (core-middle layer-shell) to spherical core-shell structure. The PEO shell thins and the size of the PLA core increases. The onionlike structures are comprised of the PEO hydrophilic core, the PLA hydrophobic middle layer, and the PEO hydrophilic shell, the distribution of the paclitaxel drug predominantly occurs within the hydrophobic intermediate layer; (ii) The system forms a spherical core-shell structure when a small amount of the drug is added, and within a certain range, the size of the spherical structure increases as the drug amount increases. When the drug contents (volume fraction) cdrug = 10%, it can be observed that the PLA4-b-PEO19-b-PLA4 spherical structures connect to form rod-shaped structures. With the length of PLA block NPLA = 8, as the paclitaxel drug concentrations cdrug = 4%, PEO has been insufficient to completely encapsulate the PLA and paclitaxel drug beads. To enhance drug loading capacity while maintaining stability of the system in aqueous solution, the optimal composition for loading paclitaxel is PLA4-b-PEO19-b-PLA4; the drug content is not higher than 4%; (iii) The paclitaxel-loaded PLA4-b-PEO19-b-PLA4 micelle undergo the transition from onionlike (core-middle layer-shell) to spherical (core-shell) to rod-shaped and lamellar structure as the PLA4-b-PEO19-b-PLA4 copolymer concentration increases from ccp = 10% to 40%.

A Biomimetic Multifunctional Scaffold for Infectious Vertical Bone Augmentation.

The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL-1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non-inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near-complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri-implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.

BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation.

Esophageal cancer ranks among the most prevalent malignant tumors, and esophageal squamous cell carcinoma (ESCC) constitutes its predominant histological form. Despite its impact, a thorough insight into the molecular intricacies of ESCC's development is still incomplete, which hampers the advancement of targeted molecular diagnostics and treatments. Recently, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has come under investigation for its potential involvement in tumor biology, yet its specific role and mechanism in ESCC remain unclear. In this study, we observed a marked increase in BCLAF1 expression in ESCC tissues, correlating with advanced tumor stages and inferior patient outcomes. Our comprehensive in vitro and in vivo studies show that BCLAF1 augments glycolytic activity and the proliferation, invasion, and spread of ESCC cells. By employing mass spectrometry, we identified YTHDF2 as a key protein interacting with BCLAF1 in ESCC, with further validation provided by colocalization, co-immunoprecipitation, and GST pull-down assay. Further investigations involving MeRIP-seq and RIP-seq, alongside transcriptomic analysis, highlighted SIX1 mRNA as a molecule significantly upregulated and modified by N6-methyladenosine (m6A) in BCLAF1 overexpressing cells. BCLAF1 was found to reduce the tumor-suppressive activities of YTHDF2, and its effects on promoting glycolysis and cancer progression were shown to hinge on SIX1 expression. This research establishes that BCLAF1 fosters glycolysis and tumor progression in ESCC through the YTHDF2-SIX1 pathway in an m6A-specific manner, suggesting a potential target for future therapeutic intervention.

Discovery and validation of anti-arthritic ingredients and mechanisms of Qingfu Juanbi Tang, a Chinese herbal formulation, on rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingfu Juanbi Tang (QFJBT), a novel and improved Chinese herbal formulation, has surged in recent years for its potential in the therapy of rheumatoid arthritis (RA). Anti-arthritic effects and underlying molecular mechanisms of QFJBT have increasingly become a focal point in research. AIM OF THE STUDY: This study utilized network pharmacology, molecular docking, and experimental validation to elucidate effective ingredients and anti-arthritic mechanisms of QFJBT. MATERIALS AND METHODS: Targets associated with QFJBT and RA were identified from relevant databases and standardized using the Uniprot for gene nomenclature. A "QFJBT-ingredient-target network" and a "Venn diagram of QFJBT and RA targets" were created from the data. The overlap in the Venn diagram highlighted potential targets of QFJBT in the treatment of RA. These targets were subjected to PPI network, GO, and KEGG pathway analysis. The findings were subsequently confirmed through molecular docking and pharmacological experiments to propose the mechanism of action of QFJBT. RESULTS: The study identified 236 active ingredients in QFJBT, with 120 predicted to be effective against RA. Molecular docking showed high binding affinity of key targets (JUN, PTGS2, and TNF-α) with bioactive compounds (rhein, sinomenine, calycosin, and paeoniflorin) of QFJBT. Pharmacodynamic evaluation demonstrated the effects of QFJBT at the dose of 4.56 g/kg in ameliorating symptoms of AIA rats and in reducing levels of JUN, PTGS2, and TNF-α in synovial tissues. In vitro studies further exhibited that rhein, paeoniflorin, sinomenine, calycosin, and QFJBT-containing serum significantly inhibited abnormal proliferation of RA fibroblast-like synoviocytes. Interestingly, rhein and paeoniflorin specifically decreased p-JUN/JUN expression and TNF-α release, respectively, while sinomenine and calycosin selectively increased PTGS2 expression. Consistently, QFJBT-containing serum demonstrated similar effects as those active ingredients identified in QFJBT did. CONCLUSIONS: QFJBT, QFJBT-containing serum, and its active ingredients (rhein, paeoniflorin, sinomenine, and calycosin) suppress inflammatory responses in RA. Anti-arthritic effects of QFJBT and its active ingredients are likely linked to their modulatory impact on identified hub targets.

CircNCX1 modulates cardiomyocyte proliferation through promoting ubiquitination of BRG1.

In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation.

Associations between emotional maltreatment, depression and self-harm among Chinese adolescents: A three-wave longitudinal mediation model.

BACKGROUND: Self-harm seriously endangers adolescents' physical and mental health. However, the longitudinal mechanism of self-harm is not yet clear. OBJECTIVE: This study explored the inconsistent relationships between two types of emotional maltreatment and self-harm across three waves, regarding depression as a potential mediator and gender as a moderator of these associations. PARTICIPANTS AND SETTING: A sample of 588 Chinese adolescents (Mage at T1 = 12.79 years) in a middle school completed the assessment of demographic information, emotional maltreatment, depression and self-harm within one year. METHODS: Path analysis models were created to estimate the relationship of emotional maltreatment with self-harm and the mediating effect of depression. A multi-group analysis was applied to investigate the moderating effect of gender. RESULTS: There existed positive associations between emotional abuse at T1 and self-harm at T2 and T3 (ß = 0.12, SE = 0.05, p = 0.006; ß = 0.09, SE = 0.05, p = 0.054), and the mediating effect of emotional abuse at T1 on self-harm at T3 via depression at T2 was significant (Indirect effect = 0.05, SE = 0.02, 95 % CI [0.02, 0.08]). Multi-group analysis of gender revealed no significant differences in the cross-lagged pathways, but there were stronger links for girls than boys among self-harm at T1, T2, and T3 (p < 0.001). CONCLUSIONS: Emotional abuse but not emotional neglect could significantly predict self-harm. Furthermore, depression played a mediating role in the longitudinal relationship between emotional abuse and self-harm. Girls who had high levels of self-harm at a previous time point were more inclined than boys to harm themselves at a subsequent time point. These findings provide a different perspective to develop effective prevention and intervention measures.

Patients with hepatocellular carcinoma extrahepatic metastases can benefit from hepatic arterial infusion chemotherapy combined with lenvatinib plus programmed Death-1 inhibitors.

BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). CONCLUSION: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.

Observation on Efficacy of Selective Malposition Ligation Combined with Hemorrhoid and Fistula I in Complex Mixed Hemorrhoid.

Objective: The efficacy of selective malposition ligation combined with hemorrhoid and fistula I prescription and the improvement of complications were assessed to improve surgical efficiency and safety. Methods: 423 patients undergoing complex mixed hemorrhoid surgery at different time points were included as research objects and enrolled into group A (malposition ligation), group B (selective malposition ligation), and group C (selective malposition ligation and hemorrhoid and fistula I), each with 141 cases. Results: The scores for visual analogue scale (VAS), edema, and hemorrhage of group C 8h, 1 day, 2 days, 3 days, 5 days, and 7 days after surgery were all inferior to those in groups A and B, while that of group B was inferior to that in group A (P < .05). The duration of wound healing of group C (15.33 ± 2.78 days) was shorter than that of groups A (21.78 ± 3.22 days) and B (18.34 ± 3.01 days), and this duration of group B was shorter than that of group A (P < .05). The total effective rate of group C (96.45%) was superior to that of groups B (96.45%) and A (82.27%). The total effective rate of group B was superior to that of group A. The falling-off rate of the rubber ring in groups C and B was inferior to that in group A. The incidence of total complications in group C (9.93%) was inferior to that in groups B (30.50%) and A (30.50%), while that of group B was inferior to that in group A (P < .05). Conclusion: After selective malposition ligation, the oral intake of hemorrhoid and fistula I could promote the recovery of wounds among patients with complex mixed hemorrhoids and reduce the incidence of postoperative hemorrhage and edema. Hence, it has significant clinical application values.

Crown adjustment and chairside efficiency of single-unit restorations fabricated from immediate and staged impressions using a digital workflow for posterior implants.

PURPOSE: This is a clinical study to compare immediate and staged impression methods in a complete digital workflow for single-unit implants in the posterior area. MATERIALS AND METHODS: Sixty patients requiring single-unit implant crowns were enrolled. Forty patients were assigned to the test group, immediate digital impression after implant surgery with crown delivery 4 months later. The remaining 20 patients were assigned to the control group, staged digital impressions 4 months after implant surgery, and crown delivery 1 month later. Both workflows involved free-model CAD-CAM crown fabrications. The crowns were scanned before and after clinical adjustment using an intraoral scanner (TRIOS Color; 3Shape). Two 3D digital models were trimmed and superimposed to evaluate the dimensional changes using Geomagic Control software. Chairside times for the entire workflow were recorded. Kruskal-Wallis was performed to compare crown adjustments between two groups, while One-way ANOVA was used to compare chairside time durations between the test and control groups. RESULTS: All crowns were delivered without refabrication. The average maximum occlusion adjustment of crowns was -353.2 ± 207.1 µm in the test group and -212.7 ± 150.5 µm in the control group (p = 0.02). The average area of occlusal adjustment, measured as an area of deviation larger than 100 µm, was 14.8 ± 15.3 and 8.4 ± 8.1 mm2 in the test and control groups, respectively (p = 0.056). There were no significant differences in the mesial and distal contact adjustment amounts, or the maximum deviations of the proximal area, between the two groups. The mean chair-side time was 50.25 ± 13.48 and 51.20 ± 5.34 min in the test and control groups, respectively (p = 0.763). CONCLUSIONS: The immediate impression method in the digital workflow for single-unit implants required more occlusal adjustments of crowns but showed similar chairside times compared to the staged impression method.

Investigating the potential causal association between consumption of green tea and risk of lung cancer: a study utilizing Mendelian randomization.

Background: Lung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer. Methods: We utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test. Results: No significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods. Conclusion: Green tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.

Digital registration versus cone-beam computed tomography for evaluating implant position: a prospective cohort study.

BACKGROUND: Postoperative cone-beam computed tomography (CBCT) examination is considered a reliable method for clinicians to assess the positions of implants. Nevertheless, CBCT has drawbacks involving radiation exposure and high costs. Moreover, the image quality can be affected by artifacts. Recently, some literature has mentioned a digital registration method (DRM) as an alternative to CBCT for evaluating implant positions. The aim of this clinical study was to verify the accuracy of the DRM compared to CBCT scans in postoperative implant positioning. MATERIALS AND METHODS: A total of 36 patients who received anterior maxillary implants were included in this clinical study, involving a total of 48 implants. The study included 24 patients in the single implant group and 12 patients in the dual implant group. The postoperative three-dimensional (3D) positions of implants were obtained using both CBCT and DRM. The DRM included three main steps. Firstly, the postoperative 3D data of the dentition and intraoral scan body (ISB) was obtained through the intraoral scan (IOS). Secondly, a virtual model named registration unit which comprised an implant replica and a matching ISB was created with the help of a lab scanner and reverse engineering software. Thirdly, by superimposing the registration unit and IOS data, the postoperative position of the implant was determined. The accuracy of DRM was evaluated by calculating the Root Mean Square (RMS) values after superimposing the implant positions obtained from DRM with those from postoperative CBCT. The accuracy of DRM was compared between the single implant group and the dual implant group using independent sample t-tests. The superimposition deviations of CBCT and IOS were also evaluated. RESULTS: The overall mean RMS was 0.29 ± 0.05 mm. The mean RMS was 0.30 ± 0.03 mm in the single implant group and 0.29 ± 0.06 mm in the dual implant group, with no significant difference (p = 0.27). The overall registration accuracy of the IOS and CBCT data ranged from 0.14 ± 0.05 mm to 0.21 ± 0.08 mm. CONCLUSION: In comparison with the 3D implant positions obtained by CBCT, the implant positions located by the DRM showed clinically acceptable deviation ranges. This method can be used in single and dual implant treatments to assess the implant positions.

A Multi-Source Data Fusion Network for Wood Surface Broken Defect Segmentation.

Wood surface broken defects seriously damage the structure of wooden products, these defects have to be detected and eliminated. However, current defect detection methods based on machine vision have difficulty distinguishing the interference, similar to the broken defects, such as stains and mineral lines, and can result in frequent false detections. To address this issue, a multi-source data fusion network based on U-Net is proposed for wood broken defect detection, combining image and depth data, to suppress the interference and achieve complete segmentation of the defects. To efficiently extract various semantic information of defects, an improved ResNet34 is designed to, respectively, generate multi-level features of the image and depth data, in which the depthwise separable convolution (DSC) and dilated convolution (DC) are introduced to decrease the computational expense and feature redundancy. To take full advantages of two types of data, an adaptive interacting fusion module (AIF) is designed to adaptively integrate them, thereby generating accurate feature representation of the broken defects. The experiments demonstrate that the multi-source data fusion network can effectively improve the detection accuracy of wood broken defects and reduce the false detections of interference, such as stains and mineral lines.

Mitochondria-targeted reactive oxygen species blockor SS-31 blocks hepatic stellate cell activation and alleviates hepatic fibrosis by regulating NLRP3 inflammasomes.

This study aimed to elucidate the effect of mitochondria-targeted reactive oxygen species (ROS) blockor SS-31 on hepatic stellate cells (HSC) activation during liver fibrosis. TGF-ß1 was employed to induce HSC activation, while MitoSOX Red was utilized to assess the presence of mitochondrial ROS. The mitochondrial membrane potential (MMP) was measured using the JC-1 probe, and the ATP level was determined using a specific kit. The proliferation of HSCs was assessed using CCK-8 and colony formation assays, whereas flow cytometry was employed to detect HSC apoptosis. Fibrotic markers (COL1A1 and α-SMA) and NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) were analyzed via Western blotting. Liver fibrosis was induced in mice using CCl4, and subsequently, histopathological changes were observed through HE staining and Masson staining. In TGF-ß1-activated HSCs, mitochondrial ROS expression increased, MMP and ATP content decreased, indicating mitochondrial damage. After TGF-ß1 induction, HSC proliferation increased, apoptosis decreased, and COL1A1, α-SMA, and NLRP3 inflammasome protein expression increased. After SS-31 treatment, mitochondrial ROS expression decreased, MMP recovered, ATP level increased, HSC proliferation decreased, apoptosis increased, and the expressions of COL1A1, α-SMA, and NLRP3 inflammasome decreased. NLRP3 blockor MCC950 treatment blocked HSC activation. CCL4-induced liver fibrosis mice had inflammatory cell infiltration and significant collagen fiber deposition in the liver. After SS-31 treatment, liver inflammation and collagen deposition were significantly reduced. SS-31, as a mitochondria-targeted ROS blockor, can block HSC activation by regulating the NLRP3 inflammasome, thereby alleviating liver fibrosis.

A modified Prussian blue biosensor with improved stability based on the use of self-assembled monolayers and polydopamine for quantitative L-glutamate detection.

A miniature L-glutamate (L-Glu) biosensor is described based on Prussian blue (PB) modification with improved stability by using self-assembled monolayers (SAMs) technology and polydopamine (PDA). A gold microelectrode (AuME) was immersed in NH2(CH2)6SH-ethanol solution, forming well-defined SAMs via thiol-gold bonding chemistry which increased the number of deposited Prussian blue nanoparticles (PBNPs) and confined them tightly on the AuME surface. Then, dopamine solution was dropped onto the PBNPs surface and self-polymerized into PDA to protect the PB structure from destruction. The PDA/PB/SAMs/AuME showed improved stability through CV measurements in comparison with PB/AuME, PB/SAMs/AuME, and PDA/PB/AuME. The constructed biosensor achieved a high sensitivity of 70.683 nA µM-1 cm-2 in the concentration range 1-476 µM L-Glu with a low LOD of 0.329 µM and performed well in terms of selectivity, reproducibility, and stability. In addition, the developed biosensor was successfully applied to the determination of L-Glu in tomato juice, and the results were in good agreement with that of high-performance liquid chromatography (HPLC). Due to its excellent sensitivity, improved stability, and miniature volume, the developed biosensor not only has a promising potential for application in food sample analysis but also provides a good candidate for monitoring L-Glu level in food production.

Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia.

The management of patients with acute myeloid leukemia (AML) remains a challenge because of the complexity and heterogeneity of this malignancy. Despite the recent approval of several novel targeted drugs, resistance seems inevitable, and clinical outcomes are still suboptimal. Increasing evidence supports the use of natural plants as an important source of anti-leukemic therapeutics. Licochalcone A (LCA) is an active flavonoid isolated from the roots of licorice, Glycyrrhiza uralensis Fisch., possessing extensive anti-tumor activities. However, its effects on AML and the underlying mechanisms remain unknown. Here, we showed that LCA decreased the viability of established human AML cell lines in a dose- and time-dependent manner. LCA significantly induced mitochondrial apoptotic cell death, accompanied by the downregulation of MCL-1, upregulation of BIM, truncation of BID, and cleavage of PARP. A prominent decline in the phosphorylation of multiple critical molecules, including AKT, glycogen synthase kinase-3ß (GSK3ß), ERK, and P38 was observed upon LCA treatment, indicating PI3K and MAPK signals were suppressed. Both transcription and translation of c-Myc were also inhibited by LCA. In addition, LCA enhanced the cytotoxicity of the BCL-2 inhibitor venetoclax. Furthermore, the anti-survival and pro-apoptotic effects were confirmed in primary blasts from 10 patients with de novo AML. Thus, our results expand the applications of LCA, which can be regarded as a valuable agent in treating AML.

Inhibition of IL-17 signaling in macrophages underlies the anti-arthritic effects of halofuginone hydrobromide: Network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear. METHODS: This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA. RESULTS: Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17 C, p-NF-κB, and MMP9. CONCLUSION: In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.

Comprehensive Therapeutic Efficacy Analysis of Intravenous Immunoglobulin in Treating Sepsis-induced Coagulopathy: A Single-Center, Retrospective Observational Study.

OBJECTIVES: To investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy (SIC). METHODS: A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People's Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared to the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days post-admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. RESULTS: On day 3 of treatment, both groups exhibited reduced PLT and TEG-MA levels, with the control group showing a more significant decrease (P < 0.05). By the 5th day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 (P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 (P < 0.05). The levels of PT, INR, APTT, D-dimer, FIB, FDP, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group (P < 0.05). Additionally, both groups showed a reduction in APACHE II, SOFA, DIC, and LAC levels on day 3, but the test group's scores decreased significantly more by day 7 (P < 0.05). Within the test group, WBC count, CRP, PCT, IL-6, and Tmax levels were lower (P < 0.05). Furthermore, the test group demonstrated shorter duration for ICU stay, mechanical ventilation, and CRRT (P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group (P < 0.05). CONCLUSION: IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC.

A newly synthesized flavone avoids COMT-catalyzed methylation and mitigates myocardial ischemia/reperfusion injury in H9C2 cells via JNK and P38 pathways.

Objectives: Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury. Materials and Methods: Luteolin and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 µmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation. Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

The Effects of Implantable Collamer Lens ICL Implantation in High Myopia Patients' Mental Health.

Purpose: To investigate the psychological changes in patients pre and post implantable collamer lens (ICL, EVO) implantation surgery in the posterior chamber. Patients and methods: Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the mental states of 43 patients who underwent ICL implantation surgery performed by the same surgeon between January 2021 and December 2022. Results: Comparing the results before and one week after the operation, there is a significant difference in both the SAS scale (P<0.05) and the SDS scale (P<0.05). Similarly, when comparing the pre-operation and one-month post-operation results, there is also a significant difference in both the SAS scale (P<0.05) and the SDS scale (P<0.05). However, when comparing the one-week post-operation and one-month post-operation results, there is no significant difference in either the SAS scale (P>0.05) or the SDS scale (P>0.05). Moving on to the comparison between the pre-operation results and the national norm level, there is a significant difference in both the SAS scale (P<0.05) and the SDS scale (P<0.05). When comparing the one-week post-operation results and the national norm level, there is a significant difference in the SAS scale (P<0.05). Similarly, when comparing the one-month post-operation results and the national norm level, there is a significant difference in the SAS scale (P<0.05). Conclusion: After undergoing ICL implantation surgery, patients typically experience a notable decrease in anxiety (SAS) and depression (SDS) scales. These improvements gradually stabilize and enhance during the postoperative recovery period. However, it may require a significant amount of time for patients to fully restore their psychological well-being to levels comparable to the national norm, particularly in terms of anxiety levels.

Screw-retained ceramic-veneered/monolithic zirconia partial implant-supported fixed dental prostheses: A 5 to 10-year retrospective study on survival and complications.

PURPOSE: To assess the clinical performance of screw-retained, ceramic-veneered, monolithic zirconia partial implant-supported fixed dental prostheses (ISFDP) over 5-10 years and to evaluate implant- and prosthesis-related factors influencing treatment failure and complications. MATERIALS AND METHODS: Partially edentulous patients treated with screw-retained all-ceramic ISFDPs with 2-4 prosthetic units with a documented follow-up of ≥5 years after implant loading were included in this retrospective study. The outcomes analyzed included implant/prosthesis failure and biological/technical complications. Possible risk factors were identified using the mixed effects Cox regression analysis. RESULTS: A screened sample of 171 participants with 208 prostheses (95% of the restorations were splinted crowns without a pontic) supported by 451 dental implants were enrolled in this study. The mean follow-up duration after prosthesis delivery was 82.4 ±17.2 months. By the end of the follow-up period, 431 (95.57%) of the 451 implants remained functional at the implant level. At the prosthesis level, 185 (88.94%) of the 208 partial ISFDPs remained functional. Biological complications were observed in 67 implants (14.86%), and technical complications were observed in 62 ISFDPs (29.81%). Analysis revealed only emergence profiles (over-contoured) as a significant risk factor for implant failure (P<0.001) and biological complications (P<0.001). Full-coverage ceramic-veneered zirconia prostheses had a significantly greater chance of chipping (P<0.001) compared with buccal-ceramic-veneered or monolithic zirconia prostheses. CONCLUSIONS: Screw-retained ceramic-veneered, monolithic partial ISFDPs have a favorable long-term survival rate. Over-contoured emergence profile is a significant risk factor associated with implant failure and biological complications. Buccal-ceramic-veneered and monolithic zirconia partial ISFDPs lower the initial prevalence of chipping compared with a full-coverage veneered design.