TGF-ß-driven LIF expression influences neutrophil extracellular traps (NETs) and contributes to peritoneal metastasis in gastric cancer.

Gastric cancer (GC), notorious for its poor prognosis, often advances to peritoneal dissemination, a crucial determinant of detrimental outcomes. This study intricately explores the role of the TGFß-Smad-LIF axis within the tumor microenvironment in propagating peritoneal metastasis, with a specific emphasis on its molecular mechanism in instigating Neutrophil Extracellular Traps (NETs) formation and encouraging GC cellular functions. Through a blend of bioinformatics analyses, utilizing TCGA and GEO databases, and meticulous in vivo and in vitro experiments, LIF was identified as pivotally associated with GC metastasis, notably, enhancing the NETs formation through neutrophil stimulation. Mechanistically, TGF-ß was substantiated to elevate LIF expression via the activation of the Smad2/3 complex, culminating in NETs formation and consequently, propelling peritoneal metastasis of GC. This revelation uncovers a novel potential therapeutic target, promising a new avenue in managing GC and mitigating its metastatic propensities.

Cross-lagged analysis of rumination and social anxiety among Chinese college students.

BACKGROUND: Social anxiety, which is widely prevalent among Chinese college students, poses a significant barrier to their holistic psychological and physiological development. Although numerous cross-sectional studies have examined the relationship between rumination and social anxiety, there is still a gap in understanding their interplay over time. This longitudinal study aimed to explore and analyze the intricate interrelations between these two factors, with the ultimate goal of informing the development of effective mental health education interventions for university students. METHODS: Using the Ruminative Responses Scale (RRS) and the Interaction Anxiousness Scale (IAS), a two-stage longitudinal follow-up study of 392 college students from three universities in Henan Province was conducted over a six-month period (October 2022 to March 2023) using a cross-lagged model to explore the correlation between rumination and social anxiety. The results of the correlation analysis showed that rumination was positively associated with social anxiety at both time points (r = 0.18,0.12, p < 0.01). RESULTS: Cross-lagged regression analyses revealed that the predictive effect of the first measure (T1) rumination on the second measure (T2) rumination was statistically significant (ß = 0.32, p < 0.001). The predictive effect of T1 social anxiety on T2 social anxiety was statistically significant (ß = 0.65, p < 0.001), the predictive effect of T1 rumination on T2 social anxiety was statistically significant (ß = 0.33, p < 0.001), and the prediction of T1 social anxiety on T2 rumination was statistically significant (ß = 0.28, p < 0.001). CONCLUSION: College students' rumination and social anxiety are mutually predictive of each other, and interventions by educators in either of these areas have the potential to interrupt the vicious cycle between ruminant thinking and social anxiety.

CRL4B E3 ligase recruited by PRPF19 inhibits SARS-CoV-2 infection by targeting ORF6 for ubiquitin-dependent degradation.

The accessory protein ORF6 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key interferon (IFN) antagonist that strongly suppresses the production of primary IFN as well as the expression of IFN-stimulated genes. However, how host cells respond to ORF6 remains largely unknown. Our research of ORF6-binding proteins by pulldown revealed that E3 ligase components such as Cullin 4B (CUL4B), DDB1, and RBX1 are potential ORF6-interacting proteins. Further study found that the substrate recognition receptor PRPF19 interacts with CUL4B, DDB1, and RBX1 to form a CRL4B-based E3 ligase, which catalyzes ORF6 ubiquitination and subsequent degradation. Overexpression of PRPF19 promotes ORF6 degradation, releasing ORF6-mediated IFN inhibition, which inhibits SARS-CoV-2 replication. Moreover, we found that activation of CUL4B by the neddylation inducer etoposide alleviates lung lesions in a SARS-CoV-2 mouse infection model. Therefore, targeting ORF6 for degradation may be an effective therapeutic strategy against SARS-CoV-2 infection.IMPORTANCEThe cellular biological function of the ubiquitin-proteasome pathway as an important modulator for the regulation of many fundamental cellular processes has been greatly appreciated. The critical role of the ubiquitin-proteasome pathway in viral pathogenesis has become increasingly apparent. It is a powerful tool that host cells use to defend against viral infection. Some cellular proteins can function as restriction factors to limit viral infection by ubiquitin-dependent degradation. In this research, we identificated of CUL4B-DDB1-PRPF19 E3 Ubiquitin Ligase Complex can mediate proteasomal degradation of ORF6, leading to inhibition of viral replication. Moreover, the CUL4B activator etoposide alleviates disease development in a mouse infection model, suggesting that this agent or its derivatives may be used to treat infections caused by SARS-CoV-2. We believe that these results will be extremely useful for the scientific and clinic communities in their search for cues and preventive measures to combat the COVID-19 pandemic.

Intra-articular injection of tranexamic acid in patients with haemophilia arthritis: retrospective controlled study in total knee arthroplasty.

PURPOSE: Total knee arthroplasty is the main method for the treatment of advanced haemophilic knee arthritis. Due to the particularity of hemophilia, the blood management plan is the focus of the perioperative period for haemophilia patients. This study aimed to investigate the clinical effect and safety of intra-articular injection of tranexamic acid in patients with haemophilia. METHODS: This is a retrospective study. According to whether tranexamic acid is used or not, patients are divided into tranexamic acid group (n=30) and non-tranexamic acid group (n=29). Total blood loss, intraoperative blood loss, complete blood count, total amount of coagulation factor VIII (FVIII) usage, coagulation biomarkers, inflammatory biomarkers, knee range of motion, knee joint function, pain status, complication rate, and patient satisfaction were assessed and compared at a mean follow-up of 16 months. RESULTS: Injecting tranexamic acid into the knee joint cavity can effectively reduce the hidden blood loss and total blood loss (P<0.001), and reduce the patient's early postoperative inflammation biomarkers, pain status, and limb swelling. Therefore, the patient can obtain a better range of motion following total knee arthroplasty. In the long run, in terms of joint function and surgical satisfaction, there are no statistically significant differences. In addition, there are no statistically significant differences between the two groups of patients in terms of the total amount of FVIII usage, length of stay, and hospitalization expenses. CONCLUSION: In patients with haemophilia, intra-articular injection of tranexamic acid during total knee arthroplasty can effectively reduce postoperative blood loss, early postoperative inflammation levels, pain and limb swelling, and enable patients to receive higher-quality rehabilitation exercises to get better joint function. Previous studies on TKA in haemophilic patients have already demonstrated the efficacy of intra-articular injections of TXA in reducing postoperative blood loss. Our study confirms this efficacy.

A Multimodal Deep Learning Framework for Predicting PPI-Modulator Interactions.

Protein-protein interactions (PPIs) are essential for various biological processes and diseases. However, most existing computational methods for identifying PPI modulators require either target structure or reference modulators, which restricts their applicability to novel PPI targets. To address this challenge, we propose MultiPPIMI, a sequence-based deep learning framework that predicts the interaction between any given PPI target and modulator. MultiPPIMI integrates multimodal representations of PPI targets and modulators and uses a bilinear attention network to capture intermolecular interactions. Experimental results on our curated benchmark data set show that MultiPPIMI achieves an average AUROC of 0.837 in three cold-start scenarios and an AUROC of 0.994 in the random-split scenario. Furthermore, the case study shows that MultiPPIMI can assist molecular docking simulations in screening inhibitors of Keap1/Nrf2 PPI interactions. We believe that the proposed method provides a promising way to screen PPI-targeted modulators.

Relationship between 25-hydroxy vitamin D and knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

Objective: In order to examine the relationship between 25-hydroxyl vitamin D and knee osteoarthritis (KOA), a meta-analysis of 8 randomized controlled trials (RCTs) publications was hereby performed. Methods: For the purpose of finding pertinent research, the databases of PubMed, Embase and the Cochrane Library were searched. Factors including tibial cartilage volume, joint space width (JSW), synovial fluid volume, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were correspondingly evaluated, and the results were expressed using SMD and 95% confidence intervals (CI). Results: The present meta-analysis evaluated the effects of vitamin D supplementation in patients with knee osteoarthritis, with 3,077 patients included. The results showed that vitamin D administration had a statistically significant impact on the amount of synovial fluid, Visual Analog Scale (VAS) and tibial cartilage. The pain and function scales of the WOMAC scale presented a statistically significant difference, and there was no discernible difference between the vitamin D and placebo groups in the stiffness scale. Additionally, bone marrow lesions and alterations in the diameter of the joint space were not influenced by the administration of vitamin D, and according to a subgroup study, a daily vitamin D supplement containing more than 2,000 IU significantly slowed the development of synovial tissue. Conclusion: Vitamin D supplementation did benefit those suffering from knee discomfort and knee dysfunction. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332033, identifier: CRD42022332033.

Emerging role of interactions between tumor angiogenesis and cancer stem cells.

Tumor angiogenesis and cancer stem cells (CSCs) are two major hallmarks of solid tumors. They have long received attention for their critical roles in tumor progression, metastasis and recurrence. Meanwhile, plenty of evidence indicates the close association between CSCs and tumor vasculature. CSCs are proven to promote tumor angiogenesis, and the highly vascularized tumor microenvironment further maintains CSCs growth in return, thereby forming a hard-breaking vicious circle to promote tumor development. Hence, though monotherapy targeting tumor vasculature or CSCs has been extensively studied over the past decades, the poor prognosis has been limiting the clinical application. This review summarizes the crosstalk between tumor vasculature and CSCs with emphasis on small-molecule compounds and the associated biological signaling pathways. We also highlight the importance of linking tumor vessels to CSCs to disrupt the CSCs-angiogenesis vicious circle. More precise treatment regimens targeting tumor vasculature and CSCs are expected to benefit future tumor treatment development.

The relationship between self-esteem and mobile phone addiction among college students: The chain mediating effects of social avoidance and peer relationships.

Introduction: Mobile phone addiction has a negative impact on the physical and mental health of college students, which has attracted extensive attention from scholars. Methods: In this study, we investigated the mechanism of the influence of self-esteem on mobile phone addiction among 694 college students using the Self-Esteem Scale, the Mobile Phone. Addiction Scale, the Peer Relationship Scale and the Social Avoidance and Distress Scale. Results: The results showed that (1) self-esteem significantly and negatively predicted mobile phone addiction; (2) self-esteem influenced mobile phone addiction through the mediating effect of social avoidance; (3) self-esteem influenced mobile phone addiction through the mediating effect of peer relationships; and (4) social avoidance and peer relationships played a chain mediating role in the influence of self-esteem on mobile phone addiction. Discussion: These findings can help researchers and educators better understand the underlying mechanisms of the relationship between self-esteem and mobile phone addiction and to provide practical and effective operational suggestions for the prevention and intervention of mobile phone addiction among college students.

Repeated neonatal Needle-pricking stimulation alter neurodevelopment in adolescent rats.

OBJECTIVE: To explore the repeated pain stimulation in neonatal rats affects their cognitive and memory abilities during puberty, and the proliferation expression of hippocampal neurons. METHODS: Postnatal 1 day (P1) SD rats were randomly divided into two groups, and the skin of the needle group was pricked for seven days consecutively while the skin of the control group was stroked for the same period of time. The rats in both groups were weighed every week, and the Morris water maze experiment was performed from P44 to P49 to test the cognitive and memory abilities of the rats. On P50, the hippocampal tissue was extracted for observation of pathological features and the expressions of Ki-67 and caspase 3 were determined. RESULTS: With the increase of the days, the body weight of the rats in the needle group increased slightly slower than that of the control group. The escape latency of the needle group was significantly higher than that of the control group in the water maze test at P45 and P48, and the number of times the rats crossing the platform in the needle group was lower than that of the control group. The HE staining of the hippocampal tissue showed that the cells in the needle group were disorganized, with irregular morphology. Under the electron microscope, the structure of neuron cells and organelles is changed in the hippocampal CA1 region of rats. It showed a decrease in the Ki-67 expression and an increase in caspase 3 in the needle group. CONCLUSION: Repeated experience of needle-pricking stimulation in neonatal rats can cause cognitive impairment and memory loss in puberty, disrupt hippocampal organization, and diminish neuronal proliferation.

Development of a gold nanoparticle-based lateral-flow strip for the detection of cannabidiol in functional beverages.

Cannabidiol (CBD), the most predominant cannabinoid, may cause addiction and liver damage. In this study, we synthesized a CBD hapten containing the carboxyl group of the spacer arm by derivatizing CBD. A highly specific and sensitive monoclonal antibody (mAb) was prepared with a half-maximal inhibitory concentration of 2.03 ng mL-1 and a limit of detection of 0.32 ng mL-1. MAb was highly specific for CBD. We developed an immunochromatographic assay (ICA) for the detection of CBD in functional beverages with a visible limit of detection of 100 ng mL-1 and a cut-off of 1000 ng mL-1. Compared with HPLC, ICA is more efficient and accurate and can be used for the rapid on-site detection of CBD in samples.

Cross-lagged analysis of problematic social media use and phubbing among college students.

BACKGROUND: Phubbing is a commonly seen phenomenon that has emerged in recent years among groups of college students, posing a rising challenge to educators. We conduct research in which the reciprocal relationship between problematic social media use and phubbing is explored and analysed quantitatively, aiming to discover reliable theoretical support to work out an appropriate intervention on students' phubbing for students' mental health concerns. METHODS: Using the problematic social media use scale and the phubbing scale, 328 college students from four universities in Shandong Province were enrolled in a two-stage longitudinal follow-up study for 20 months from December 2019 to August 2021. A cross-lagged model was constructed to explore the reciprocal relationship between problematic social media use and phubbing. The results of correlation analysis showed that problematic social media use was positively correlated with phubbing at both time points (r = 0.51, 0.53, P < 0.01). RESULTS: The results of cross-lagged regression analysis showed that the predictive effect of pretest problematic social media use on posttest problematic social media use was statistically significant (ß = 0.24, P < 0.01). There was statistical significance in the prediction effect of pretest phubbing on posttest phubbing (ß = 0.16, P < 0.05). Pretest problematic social media use had statistical significance in predicting posttest phubbing (ß = 0.22, P < 0.01), and there was no statistical significance in the prediction of pretest phubbing on posttest problematic social media (ß = 0.16, P < 0.05). CONCLUSION: The problematic social media use of college students is closely related to phubbing, and problematic social media use can predict phubbing.

Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway.

Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 µM caffeine), antagonist (5 µM ZM241385), agonist (5 µM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. Caffeine and A2AR may serve as a promising therapeutic target for BPD in prematurity.

The Relationship Between Study Engagement and Critical Thinking Among Higher Vocational College Students in China: A Longitudinal Study.

Purpose: Numerous cross-sectional studies have explored the correlation between study engagement and critical thinking, but the relationship between the development of these two key variables over time is unclear and the causal relationship between them remains controversial. In this study, we examined the developmental trajectories of and the interplay between study engagement and critical thinking. Methods: We used a questionnaire method to follow 654 first-year students in Chinese higher vocational college over a period of one year and three times, of which 231 (35.321%) were male and 423 (64.679%) were female, with an average age of 18.11 years. Descriptive statistics were used to present general characteristics of the study participants, and latent growth model was used to explore the developmental trajectories of study engagement and critical thinking, and to explore the interplay between study engagement and critical thinking from a developmental perspective. Based on this, a cross-lagged model was used to verify the causal relationship between study engagement and critical thinking. Results: During the first year of higher vocational college in China, students' levels of study engagement and critical thinking declined continuously. The initial level and development of study engagement can positively influence the initial level and development of critical thinking, respectively, while the initial level and development of critical thinking can in turn positively influence the initial level and development of study engagement, respectively. Study engagement and critical thinking can predict each other. Conclusion: The above results help researchers and educators to develop study engagement and critical thinking in higher vocational college students from a developmental perspective. The development of either aspect of study engagement and critical thinking can contribute to the joint improvement of both.

An Immunochromatographic Assay for the Rapid and Qualitative Detection of Mercury in Rice.

Mercury is a major pollutant in food crops. In this study, we synthesized an anti-mercury monoclonal antibody (mAb; IC50 was 0.606 ng mL-1) with high sensitivity and specificity and different immunogens and coating antigens and developed an immuno-chromatographic assay (ICA) for the detection of mercury in rice. The ICA strip had a visible detection limit of 20 ng g-1 and a cut-off value of 500 ng g-1 in rice. The performance of the ICA strip was consistent with that of ICP-MS and ic-ELISA. The recoveries of mercury in rice ranged from 94.5% to 113.7% with ic-ELISA and from 93.6% to 116.45% with ICP-MS. Qualitative analysis by ICA can be obtained with the naked eye. The ICA strip is an effective and practical method for the rapid and high-throughput determination of mercury in rice.

Randomized controlled trial for time-restricted eating in overweight and obese young adults.

Time-restricted eating (TRE) is known to improve metabolic health, whereas very few studies have compared the effects of early and late TRE (eTRE and lTRE) on metabolic health. Overweight and obese young adults were randomized to 6-h eTRE (eating from 7 a.m. to 1 p.m.) (n = 21), 6-h lTRE (eating from 12 p.m. to 6 p.m.) (n = 20), or a control group (ad libitum intake in a day) (n = 19). After 8 weeks, 6-h eTRE and lTRE produced comparable body weight loss compared with controls. Compared with control, 6-h eTRE reduced systolic blood pressure, mean glucose, fasting insulin, insulin resistance, leptin, and thyroid axis activity, whereas lTRE only reduced leptin. These findings shed light on the promise of 6-h eTRE and lTRE for weight loss. Larger studies are needed to assess the promise of eTRE to yield better thyroid axis modulation and overall cardiometabolic health improvement.

Total knee arthroplasty in Ranawat II valgus deformity with enlarged femoral valgus cut angle: A new technique to achieve balanced gap.

BACKGROUND: Nearly 10% of patients undergoing primary total knee arthroplasty (TKA) have valgus deformity (VD) of the knee. For severe VD of the knee, a more lateral structural release is needed to achieve balance between medial and lateral space and neutral femorotibial mechanical axis (FTMA), which is challenging and technical. AIM: To introduce a new surgical technique of resection, soft tissue release, and FTMA for Ranawat type-II VD with a 5-year follow-up. METHODS: A retrospective study was conducted on patients who underwent TKA from December 2011 to December 2014. Hip-knee-ankle (HKA), range of motion (ROM), Oxford knee score (OKS), and knee society score (KSS) were used to assess the joint activity of patients in the new theory TKA group (NT-TKA) and were compared with those of the conventional TKA group (C-TKA). RESULTS: A total of 103 people (103 knees) were included in this study, including 42 patients with an average follow-up period of 83 mo in the C-TKA group and 61 patients with an average follow-up period of 76 mo in the NT-TKA group. Six patients had constrained prosthesis, one had common peroneal nerve injury, and two had joint instability in the C-TKA group, but none of these occurred in the NT-TKA group. There were significant statistical differences in constrained prosthesis usage and complications between the groups (P = 0.002 and P = 0.034, respectively). The KSS at 1 mo post-operation for the C-TKA and NT-TKA groups were 11.2 ± 3.8 and 13.3 ± 2.9, respectively, with a significant difference (P = 0.007). However, the data of HKA, ROM, OKS KSS, and prosthesis survival rate were insignificant (P > 0.05) in both the preoperative and follow-up periods. CONCLUSION: Adopting 5°-7° valgus cut angle for VD and sacrificing 2° neutral FTMA for severe VD which cannot be completely corrected during TKA can reduce the need for soft tissue release, maintain early joint stability, reduce the use of constrained prostheses, and minimize postoperative complications.

Long-term changes in insula-mesolimbic structural and functional connectivity in obese patients after laparoscopic sleeve gastrectomy.

OBJECTIVE: Brain imaging studies have shown insula-related functional and structural abnormalities in patients with obesity. Laparoscopic sleeve gastrectomy is currently an effective procedure for treating obesity, which promotes acute recovery of brain functional and structural abnormalities in obese patients. The aim of this study was to investigate the long-term impact of laparoscopic sleeve gastrectomy on insula-related structural and functional connectivity. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging were employed to investigate laparoscopic sleeve gastrectomy-induced changes in insula-related structural connectivity and corresponding resting-state functional connectivity in 25 obese patients prior to (PreLSG) and 12 months post-surgery (PostLSG12). RESULTS: Results showed significant increases in fractional anisotropy and axial diffusivity between the right insula and anterior cingulate cortex, and higher fractional anisotropy of left insula-putamen, left insula-caudate and anterior cingulate cortex-right posterior cingulate cortex/precuneus at PostLSG12 compared with PreLSG. There were significant negative correlations between axial diffusivity of right insula-anterior cingulate cortex and body mass index, and fractional anisotropy of right insula-anterior cingulate cortex with scores on external eating at PostLSG12. Anxiety and depressive status ratings were negatively correlated with fractional anisotropy of left insula-putamen at PostLSG12. In addition, there was a significant decrease in resting-state functional connectivity between left insula and left caudate. CONCLUSIONS: These findings demonstrate long-term changes in insula-related structural and functional connectivity abnormalities promoted by laparoscopic sleeve gastrectomy, which highlight its strong association with long-term weight loss and improvement in eating behaviors.

Bilateral synchronous total hip arthroplasty for end-stage arthropathy in hemophilia A patients: A retrospective study.

Total hip arthroplasty (THA) has been an effective tool of advanced hemophiliac hip arthritis. There are only limited data of bilateral synchronous THA for end-stage arthropathy in hemophilia A patients. The aim of this retrospective study was to analyze clinical outcome and complication rate of bilateral THA for hemophilia A patients with end-stage arthropathy of hip and review the operative strategy. From August 2012 to July 2016, 48 hips of 24 patients with hemophilia A patients underwent THA by a single experienced chief orthopedic surgeon. Clinical and radiological evaluations were included of operation time, blood loss, the quantity of blood transfusion, clotting factor consumption, duration of hospitalization, modified Harris hip score, complication rate, and radiographic assessment. All the 24 patients successfully completed the operation, followed up for 5 to 8 years, and the mean time was 6.5 years. The average operation time was 140 minutes (range, 120-180 minutes). The average total blood loss was 225 mL (range, 150-400 mL). The mean red blood cell transfusion amount was 2.4 U (range, 0-6 U). the mean hospitalization time was 24 days (range, 16-46 days). The mean amount of clotting factor VIII used in the perioperative period for management of hemophilia A was 30,600 U (range, 18,000-52,000 U). Average modified Harris hip score increased from 46.6 (range 28-70) points preoperatively to 90.2 (range 75-98) points at final follow-up, complications were few. With excellent operative techniques and hematological management, bilateral synchronous THA for end-stage arthropathy in hemophilia A patients can provide satisfactory outcomes.

Hidden blood loss of total knee arthroplasty in hemophilia arthritis: an analysis of influencing factors.

BACKGROUND: Total knee arthroplasty is the leading way to treat hemophilia arthritis. At present, there is a lack of research on the influencing factors of blood loss in total knee arthroplasty for hemophilia arthritis. This study comprehensively explores the definite factors affecting the hidden blood loss in total knee arthroplasty for hemophilia patients. MATERIALS AND METHODS: Ninety-two hemophilia A patients who underwent total knee arthroplasty in our center were included. Demographics, laboratory data, surgical data, and complications were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multivariate linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: The hidden blood loss of hemophilia A patients undergoing total knee arthroplasty was 1069.51 ± 341.99 mL, and the age was positively correlated with the hidden blood loss (P < 0.001), while tranexamic acid, FVIII prophylaxis, and incremental invivo recovery were negatively correlated with the hidden blood loss (P < 0.001, P = 0.008, P = 0.017). CONCLUSION: Elderly patients have a greater risk of blood loss, and additional preventive measures can be appropriately added. Intraoperative intra-articular injection of tranexamic acid is recommended to reduce hidden blood loss, FVIII prophylaxis is recommended for every patient. We recommend that all HA patients measure the incremental invivo recovery and develop a personalized infusion regimen of coagulation factor.

Gastric cancer cell-derived extracellular vesicles elevate E2F7 expression and activate the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12.

Cancer cell-derived extracellular vesicles (EVs) have extensive application in the formation of their environment, including metastasis. This study explored the ability of gastric cancer (GC) cell-derived EVs-mediated microRNA-129-5p/E2F transcription factor 7/mitogen-activated protein kinase/extracellular regulated protein kinase (miR-129-5p/E2F7/MAPK/ERK) axis to affect the peritoneal metastasis of GC by delivering lncRNA small nucleolar RNA host gene 12 (SNHG12). EV-derived lncRNA and SNHG12/miR-129-5p/E2F7 network were determined by bioinformatics analysis. The regulatory relationship among SNHG12, miR-129-5p, and E2F7 was verified using a combination of dual-luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays. The SNHG12, miR-129-5p, and E2F7 expression was measured by RT-qPCR. After GC cell-derived EVs were isolated and co-cultured with human peritoneal mesothelial cells (HPMCs), the uptake of EVs by HPMCs was observed under laser scanning confocal microscopy. Cell viability and apoptosis were examined using cell counting kit-8 and flow cytometry, respectively. Western blot analysis was performed to measure the mesothelial-mesenchymal transition (MMT)-related protein expression. The pathological and morphological characteristics of metastatic tumors in nude mice were observed by hematoxylin-eosin staining. A high SNHG12 expression was correlated with the poor prognosis of patients with GC. GC-derived EVs led to increased HPMC apoptosis and MMT by transferring SNHG12, whereas the knockdown of SNHG12 annulled the aforementioned results. SNHG12 sponged miR-129-5p to boost E2F7 expression and activate the MAPK/ERK signaling, thus inducing HPMC apoptosis and MMT. In vivo experiments further verified that EVs derived from GC cells promoted peritoneal metastasis in nude mice. GC cell-derived EVs elevated the E2F7 expression and activated the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12.