Impact of contextual factors on the evaluation outcomes of national virtual simulation experimental teaching projects in biology and medicine.

The number of applications for National Virtual Simulation Experimental Teaching Projects (NVSETPs) in China has seen a significant increase. Consequently, the influence of contextual factors and their potential personal connections on the evaluation results, whether for national or non-national NVSETPs, has become a prominent concern. In this study, we employed a modified back-chaining method using logistic regression to examine whether contextual factors in NVSETP applications could explain the evaluation outcomes. Our analysis was based on data available on the open platform of China's Ministry of Education (MOE). We identified several significant influencing factors, including the score on a five-point rating system, the number of clicks on the application page, school quality, school region, and the gender, title, and position of the applicants. Our results shed light on the impact of contextual factors on the evaluation results of NVSETPs in the fields of biology and medicine, using a modified back-chaining method. We conclude that enhancing the transparency of the assessment process and implementing standardized, detailed scoring guidelines for NVSETPs would mitigate the negative influence of contextual factors.

Impact of vertical alveoloplasty on changes in keratinized mucosa width following full-arch immediate implant placement and rehabilitations: A prospective case series.

PURPOSE: This prospective case series aimed to investigate the effect of vertical alveoloplasty on the changes in keratinized mucosa width (KMW) following full-arch immediate implant placement and rehabilitation. MATERIALS AND METHODS: A total of 17 potential edentulous patients were enrolled and received implant placement and full-arch implant-supported immediate rehabilitations. The main outcome was to analyze the effect of vertical alveoloplasty on the changes in KMW. The amount of vertical alveoloplasty during implant surgery as well as the changes in KMW at buccal aspects from the day of surgery to 6 months post-surgery were recorded on the implant-level using a periodontal probe. The secondary outcome was to analyze the other possible factors that affected the changes in KMW. The included factors were the initial KMW, the distribution of implants in the maxilla and mandible, the distribution of implants in the anterior and posterior regions, the distribution of implants in extraction sockets and healed ridges, and gender. Mann-Whitney non-parametric tests and multiple linear regression adjusted by generalized estimating equations (GEE) were used to statistically analyze the data. RESULTS: A total of 121 implant positions were analyzed. The KMW was 4.1± 2.0 mm on the day of the surgery and 4.1± 1.7 mm 6 months post-surgery. The mean changes in KMW following 6 months were -0.1± 1.6 mm (p = 0.824). From the results of GEE, the vertical amount of alveoloplasty had no significant effect on changes in KMW. Both initial KMW and the distribution of implants in the anterior and posterior regions had significant impacts on the changes in KMW (p < 0.0001). CONCLUSION: The amount of vertical alveoloplasty during implant surgery has no significant impact on the KMW. The KMW remained stable from baseline to 6 months after alveoloplasty, implant placement, and immediate rehabilitations in potential edentulous arches. The initial KMW and the distribution of implants in the anterior and posterior regions were the possible factors affecting changes in KMW.

Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes.

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.

Comparison of Terminal Elbow Extension between Humans and Baboons (Papio anubis).

It is assumed that hyperextension of the elbow joint beyond 0° in humans is due to local ligament and other soft tissue laxity. The common extant old-world olive baboon (Papio anubis), with a quadrupedal gait, commonly has a mild elbow joint flexion contracture. This study compares anatomic and functional roles of the olecranon-coronoid notch angle of the proximal ulna and the anterior direction of its opening on terminal elbow extension in humans and baboons. Active terminal elbow extension was measured in 211 elbows of skeletally mature humans using the neutral zero method. Passive elbow extension and radiographs were performed on 60 extremities of 30 anesthetized baboons. The mean olecranon-coronoid notch angle for humans and baboons was 22.2 ± 6.0° and 11.3 ± 3.2°, respectively (P < 0.001). Mixed effect regression analysis showed that the magnitude of the angle was a significant predictor of terminal elbow extension (P < 0.001) when accounting for species. Also, the causal mediation analysis showed that 18% of the difference in terminal elbow extension between species could be attributed to the olecranon-coronoid notch angle (P < 0.001). Anatomic dissection of 16 baboon arms showed that sectioning of all the anterior soft tissue structures increased mean terminal elbow extension from -18.2 ± 5.9° to -7.1 ± 6.0° and that further elbow extension was blocked primarily by the intact humeroulnar joint. The size of the notch angle and the positioning of its anterior proximal opening played a significant role in deciding terminal elbow extension in both species.

Improvement of the Upper Detection Limit of Ionophore-Based H+-Selective Electrodes: Explanation and Elimination of Apparently Super-Nernstian Responses.

The response range of an ion-selective electrode (ISE) has been described by counterion interference at the lower and Donnan failure at the upper detection limit. This approach fails when the potentiometric response at the upper detection limit exhibits an apparently super-Nernstian response, as has been reported repeatedly for H+-selective electrodes. While also observed when samples contain other anions, super-Nernstian responses at low pH are a problem in particular for samples that contain phthalate, a common component of commercial pH calibration solutions. This work shows that coextraction of H+ and a sample anion into the sensing membrane alone does not explain these super-Nernstian responses, even when membrane-internal diffusion potentials are taken into account. Instead, these super-Nernstian responses are explained by the formation of complexes between that anion and at least two protonated ionophore molecules. As demonstrated by experiments and explained with quantitative phase boundary models, the apparently super-Nernstian responses at low pH can be eliminated by restricting the molecular ratio of ionophore and ionic sites. Notably, this conclusion results in recommendations for the optimization of sensing membranes that, in some instances, will conflict with previously reported recommendations from the ionic site theory for the optimization of the lower detection limit. This mechanistic insight is key to maximizing the response range of these ionophore-based ISEs.

Proton beam spot size and position measurements using a multi-strip ionization chamber.

PURPOSE: To develop and characterize a large-area multi-strip ionization chamber (MSIC) for efficient measurement of proton beam spot size and position at a synchrotron-based proton therapy facility. METHODS AND MATERIALS: A 420 mm x 320 mm MSIC was designed with 240 vertical strips and 180 horizontal strips at 1.75 mm pitch. The MSIC was characterized by irradiating a grid of proton spots across 17 energies from 73.5 MeV to 235 MeV and comparing to simultaneous measurements made with a reference Gafchromic EBT3 film. Beam profiles, spot sizes, and positions were analyzed. Short term measurement stability and sensitivity were evaluated. RESULTS: Excellent agreement was demonstrated between the MSIC and EBT3 film for both spot size and position measurements. Spot sizes agreed within ± 0.18 mm for all energies tested. Measured beam spot positions agreed within ± 0.17 mm. The detector showed good short term measurement stability and low noise performance. CONCLUSION: The large-area MSIC enables efficient and accurate proton beam spot characterization across the clinical energy range. The results indicate the MSIC is suitable for pencil beam scanning proton therapy commissioning and quality assurance applications requiring fast spot size and position quantification.

Education, Language, and Cultural Concordance Influence Patient-Physician Communication in Orthopaedics.

BACKGROUND: Orthopaedic surgery has a diversity gap, as it is not representative of the racial or sex proportions of the U.S. population. This gap can lead to communication barriers stemming from health literacy, language proficiency, or cultural discordance that may contribute to current health inequities. This study assesses the influence of educational attainment, language, and cultural concordance on patient-physician communication. METHODS: In this cross-sectional study, 394 patients from an urban orthopaedic clinic were administered a Likert-type survey regarding race or ethnicity, educational level, communication, patient satisfaction, language proficiency, and culture. One-way analysis of variance, chi-square tests, and Welch t tests were used to evaluate responses. RESULTS: The majority of subjects identified as African-American/Black (50%) or Hispanic/Latino (30%). Completing high school was associated with a better ability of the subjects to communicate with their orthopaedic surgeon (p < 0.001). Hispanic subjects reported lower English proficiency (p < 0.001) and decreased ability to communicate with their physician (p < 0.001) compared with other subjects, with educational attainment influencing their ability to understand their orthopaedic surgeon in English (p < 0.001). African-American and Hispanic patients placed greater importance on orthopaedic surgeons understanding their culture than White patients (p < 0.001). Hispanic patients who saw a language and culture-concordant surgeon valued having a Spanish-speaking surgeon more than Hispanic patients who did not see a concordant surgeon (p = 0.04). CONCLUSIONS: These results suggest that patient-physician language concordance, particularly in patients with lower education, may be essential to delivering high-quality patient care. Hispanic and African-American patients placed significantly greater importance on their orthopaedic surgeons understanding their culture. Hispanic patients frequently sought care with language-concordant surgeons and placed higher value on physicians understanding their culture. To better serve minority communities, efforts should be made to increase orthopaedic surgeons' cultural humility and to recruit a diverse multilingual surgeon workforce. CLINICAL RELEVANCE: This research demonstrates that cultural and language concordance, specifically between Hispanic patients and Hispanic, Spanish-speaking surgeons, can significantly enhance patient preference and potentially improve patient satisfaction and outcomes in orthopaedic care. Additionally, it underscores the importance of understanding and addressing the diversity within the field and the patient population to better meet the needs of a multicultural society.

Specific electromyography characteristics can distinguish longitudinally extensive transverse myelitis from congestive myelopathy due to spinal dural arteriovenous fistula: a retrospective study.

Aims/Background Although electromyography has been extensively used in the diagnosis of neurological diseases, there is no comprehensive understanding of the electromyography manifestations of spinal dural arteriovenous fistula. Given the widespread use of electromyography in the diagnosis of neurological conditions, it is worthwhile to holistically analyse the electromyography findings of spinal dural arteriovenous fistula to differentiate it from neurological diseases that share similar clinical manifestations. The aim of this study is to evaluate whether electromyography can distinguish spinal dural arteriovenous fistula from longitudinally extensive transverse myelitis. Methods We holistically reviewed files of all patients who were diagnosed with spinal dural arteriovenous fistula or longitudinally extensive transverse myelitis at The First Medical Centre of PLA General Hospital from 1 January 2010 to 31 December 2020. We compared the symptomology, epidemiology, and imaging results of patients with spinal dural arteriovenous fistula and longitudinally extensive transverse myelitis, placing emphasis on their electromyography manifestations. Student's t test was used to analyse normally distributed data, while Chi-square test was used to compare classification statistics. Results Lesions of spinal dural arteriovenous fistula shown on images tend to appear at lower lumbar and sacral segments, whereas lesions of the cervical and upper thoracic segments are more characteristic of longitudinally extensive transverse myelitis. Spinal dural arteriovenous fistula patients and longitudinally extensive transverse myelitis patients overlap in terms of clinical manifestations. After comparison, the two groups of patients had different demographics (age, sex), onset mode, predisposing factors before onset, and electromyographic features. The electromyographic features of patients with spinal dural arteriovenous fistula were associated with neurogenic damage (p < 0.001). Conclusions In patients with spinal dural arteriovenous fistula, electromyography can help clinicians to identify early disease, avoid patient treatment delay, and eliminate unnecessary treatment.

Prolactin upregulates amino acids uptake in dairy cow mammary epithelial cells via LAT1.

The uptake of AA in mammary tissues is affected by prolactin (PRL). To investigate whether PRL-induced AA uptake is involved in L-type AA transporter 1 (LAT1), we analyzed the changes of AA in the medium of dairy cow mammary epithelial cells in the presence of PRL or PRL plus BCH, an inhibitor of LAT1. Then Western blot and luciferase assay were used to detect the regulation mechanism of PRL on LAT1 expression and function. Our results showed that Thr, Val, Met, Ile, Leu, Tyr, Lys, Phe, and His are LAT1 substrates and could be transported into mammary epithelial cells via LAT1. PRL stimulation increased the uptake of most AA into mammary epithelial cells of dairy cows, however, inhibition of LAT1 transport activity reduced PRL-induced AA uptake, suggesting that the effect of PRL on AA transport depends on LAT1 expression and function. PRL stimulation upregulated LAT1 expression and plasma membrane location not only in dairy cow mammary epithelial cells, but also in mouse mammary epithelial cell line HC11. Western blot showed that PI3K-AKT-mTOR signaling could be activated in PRL-stimulated mammary epithelial cells. Treatment of cells with LY294002 decreased PI3K-AKT-mTOR activation, as well LAT1 expression, that in turn decreased milk protein synthesis. Luciferase assay showed PRL treatment increased the promoter activity of LAT1 promoter fragment -419∼-86 bp. Treatment of cells with LY294002, an inhibitor of PI3K, or SC79, an activator of AKT abolished or promoted the transcriptional activity of this promoter fragment in the presence of PRL. These results suggested that the -419∼-86 bp fragment of LAT1 promoter mediates the action of PI3K-AKT-mTOR signaling on LAT1 transcription in mammary epithelial cells of dairy cows, which in turn increased LAT1 expression and AA uptake.

Enhancing Osteogenic Potential: Controlled Release of Dopamine D1 Receptor Agonist SKF38393 Compared to Free Administration.

Osteoporosis is the most common metabolic bone disorder and is characterized by decreased bone density, which has a relationship with the quality of life among the aging population. Previous research has found that activation of the dopamine D1 receptor can improve bone mass formation. SKF38393 is an agonist of dopamine D1 receptors. However, as a small-molecule drug, SKF38393 is unstable and releases quickly. The aim of this study was to prototype polylactic-co-glycolic acid (PLGA)/SKF38393 microspheres and assess their potential osteogenic effects compared to those under the free administration of SKF38393. The cytocompatibility of PLGA/SKF38393 was determined via CCK-8 and live/dead cell staining; the osteogenic effects in vitro were determined with ALP and alizarin red staining, qRT-PCR, and Western blotting; and the in vivo effects were assessed using 25 Balb/c mice. We also used a PCR array to explore the possible signaling pathway changes after employing PLGA/SKF38393. Our experiments demonstrated that the osteogenic effect of D1Rs activated by the PLGA/SKF38393 microsphere was better than that under free administration, both in vitro and in vivo. According to the PCR array, this result might be associated with six signaling pathways (graphical abstract). Ultimately, in this study, we prototyped PLGA/SKF38393, demonstrated its effectiveness, and preliminarily analyzed its mechanism of action.

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.

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%.

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.

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.

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 multicenter 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.

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.

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.

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.