A scoring system to predict the technical difficulty of endoscopic resection for cardial submucosal tumors.

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.

Non­contact locking plate: A useful alternative to external fixation in second­stage treatment of post­traumatic tibial osteomyelitis.

The treatment of infected tibial bone defects can be challenging for the orthopedic surgeon. Therefore, the aim of the present study was to compare the fixation endurance, bone union time, lower limb joint function and complications associated with different fixation methods in the treatment of bone defects caused by debridement in the treatment of post-traumatic osteomyelitis. The clinical data of 55 patients with infected bone defects of the lower extremities following traumatic injury, who had undergone radical debridement between January 2017 and September 2020, were retrospectively analyzed. The patients were divided into three groups according to the type of fixation during reconstruction, namely the external fixation (EX), internal fixation (IX) and non-contact locking plate (LP) groups. The demographic data, time to bone union, bacterial culture results, complications and Self-Rating Anxiety Scale (SAS) scores of the patients were compared among the three groups. The results indicated that the differences in time to bone union and recurrence rates of osteomyelitis among the three groups were not statistically significant. By contrast, functional status after surgery was significantly higher in the LP group compared with the EX group. In total, 8/22 patients (36.4%) in the EX group, 4/13 patients (30.8%) in the IX group and 4/20 patients (20.0%) in the non-contact LP group had shortened limbs and deformed tibia. The SAS assessment results revealed that patients in the non-contact LP group had the lowest rates of moderate and severe anxiety. In conclusion, the results of the present study demonstrate that the non-contact locking plate technique provided stable fixation without any contact between the implant and bone tissues. Therefore, this technique may be viable for use during the reconstruction stage of post-traumatic tibial osteomyelitis.

Malaria cases in China acquired through international travel, 2013-2022.

BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination. METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics. RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work. CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis.

OBJECTIVE/MAIN OUTCOME: To study the expression of OX40 on T follicular helper (Tfh) cells and the ligand OX40L on antigen-presenting cells (APCs) in peripheral blood of patients with Type 1 diabetes mellitus (T1DM) and the role of OX40 signaling in promoting Tfh cells to assist B-cell differentiation. DESIGN: Cross-sectional study. SETTING: Endocrinology department of a university hospital. PARTICIPANTS: Twenty-five patients with T1DM and 35 with newly diagnosed T2DM from January 2021-December 2021 (39 males, 21 females; mean age: 31.0 ± 4.5, range: 19-46 years). INTERVENTIONS: None. METHODS: The peripheral blood proportion of CD4+CD25-CD127+CXCR5+PD1+ Tfh cells in patients with T1DM or T2DM and the OX40L expression in CD14+ monocytes and CD19+ B cells were analyzed by flow cytometry. The OX40 signal effect on Tfh-cell function was analyzed by co-incubating B cells with Tfh cells under different conditions. Flow cytometry detected the ratio of CD19-CD138+ plasmacytes. RESULTS: The Tfh cells ratio and intracellular IL-21 expression in peripheral blood was significantly higher in patients with T1DM than with T2DM, and the OX40 expression in peripheral Tfh cells and OX40L expression in APC were significantly higher in T1DM. After adding OX40L protein, the CD19-CD138+-plasmacytes percentage was significantly increased and higher in T1DM. Blocking of anti-OX40L monoclonal antibodies significantly reduced the plasmacytes ratio. CONCLUSIONS: The peripheral Tfh cells proportion increased and the OX40 expression in peripheral Tfh cells was upregulated in patients with T1DM versus patients with T2DM. OX40/OX40L signaling enhanced the Tfh-cell function to assist B-cell differentiation, which may contribute to the pathogenesis of T1DM.

A systematic review and meta-analysis of short-term outcomes comparing the efficacy of robotic versus laparoscopic colorectal surgery in obese patients.

This meta-analysis was conducted to evaluate and contrast the effectiveness of robotic-assisted and laparoscopic colorectal surgery in the treatment of obese patients. In February 2024, we carried out an exhaustive search of key global databases including PubMed, Embase, and Google Scholar, limiting our focus to studies published in English and Chinese. We excluded reviews, protocols lacking published results, articles derived solely from conference abstracts, and studies not relevant to our research objectives. To analyze categorical variables, we utilized the Cochran-Mantel-Haenszel method along with random-effects models, calculating inverse variances and presenting the outcomes as odds ratios (ORs) along with their 95% confidence intervals (CIs). Statistical significance was determined when p values were less than 0.05. In our final meta-analysis, we included eight cohort studies, encompassing a total of 5,004 patients. When comparing the robotic surgery group to the laparoscopic group, the findings revealed that the robotic group experienced a longer operative time (weighted mean difference (WMD) = 37.53 min, 95% (CI) 15.58-59.47; p = 0.0008), a shorter hospital stay (WMD = -0.68 days, 95% CI -1.25 to -0.10; p = 0.02), and reduced blood loss (WMD = -49.23 mL, 95% CI -64.31 to -34.14; p < 0.00001). No significant differences were observed between the two groups regarding overall complications, conversion rates, surgical site infections, readmission rates, lymph node yield, anastomotic leakage, and intestinal obstruction. The results of our study indicate that robot-assisted colorectal surgery offers benefits for obese patients by shortening the length of hospital stay and minimizing blood loss when compared to laparoscopic surgery. Nonetheless, it is associated with longer operation times and shows no significant difference in terms of overall complications, conversion rates, rehospitalization rates, and other similar metrics.

Harnessing artificial intelligence for prostate cancer management.

Prostate cancer (PCa) is a common malignancy in males. The pathology review of PCa is crucial for clinical decision-making, but traditional pathology review is labor intensive and subjective to some extent. Digital pathology and whole-slide imaging enable the application of artificial intelligence (AI) in pathology. This review highlights the success of AI in detecting and grading PCa, predicting patient outcomes, and identifying molecular subtypes. We propose that AI-based methods could collaborate with pathologists to reduce workload and assist clinicians in formulating treatment recommendations. We also introduce the general process and challenges in developing AI pathology models for PCa. Importantly, we summarize publicly available datasets and open-source codes to facilitate the utilization of existing data and the comparison of the performance of different models to improve future studies.

CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer.

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

Use of Dengvaxia® in Australian Travellers: a case series.

Dengvaxia is the only licensed dengue vaccine in Australia, but rarely used. We report the experience of using Dengvaxia in seven Australian travellers. Main reasons for opting for vaccination were travel to dengue-endemic regions and severe symptoms during the prior dengue infection. The vaccine was well tolerated by all travellers.

Substantial viral diversity in bats and rodents from East Africa: insights into evolution, recombination, and cocirculation.

BACKGROUND: Zoonotic viruses cause substantial public health and socioeconomic problems worldwide. Understanding how viruses evolve and spread within and among wildlife species is a critical step when aiming for proactive identification of viral threats to prevent future pandemics. Despite the many proposed factors influencing viral diversity, the genomic diversity and structure of viral communities in East Africa are largely unknown. RESULTS: Using 38.3 Tb of metatranscriptomic data obtained via ultradeep sequencing, we screened vertebrate-associated viromes from 844 bats and 250 rodents from Kenya and Uganda collected from the wild. The 251 vertebrate-associated viral genomes of bats (212) and rodents (39) revealed the vast diversity, host-related variability, and high geographic specificity of viruses in East Africa. Among the surveyed viral families, Coronaviridae and Circoviridae showed low host specificity, high conservation of replication-associated proteins, high divergence among viral entry proteins, and frequent recombination. Despite major dispersal limitations, recurrent mutations, cocirculation, and occasional gene flow contribute to the high local diversity of viral genomes. CONCLUSIONS: The present study not only shows the landscape of bat and rodent viromes in this zoonotic hotspot but also reveals genomic signatures driven by the evolution and dispersal of the viral community, laying solid groundwork for future proactive surveillance of emerging zoonotic pathogens in wildlife. Video Abstract.

Thermal Stability and Crystallization Processes of Pd78Au4Si18 Thin Films Visualized via In Situ TEM.

Amorphous alloys or metallic glasses (MGs) thin films have attracted extensive attention in various fields due to their unique functional properties. Here, we use in situ heating transmission electron microscopy (TEM) to investigate the thermal stability and crystallization behavior of Pd-Au-Si thin films prepared by a pulsed laser deposition (PLD) method. Upon heating treatment inside a TEM, we trace the structural changes in the Pd-Au-Si thin films through directly recording high-resolution images and diffraction patterns at different temperatures. TEM observations reveal that the Pd-Au-Si thin films started to nucleate with small crystalline embryos uniformly distributed in the glassy matrix upon approaching the glass transition temperature Tg=625K, and subsequently, the growth of crystalline nuclei into sub-10 nm Pd-Si nanocrystals commenced. Upon further increasing the temperature to 673K, the thin films transformed to micro-sized patches of stacking-faulty lamellae that further crystallized into Pd9Si2 and Pd3Si intermetallic compounds. Interestingly, with prolonged thermal heating at elevated temperatures, the Pd9Si2 transformed to Pd3Si. Simultaneously, the solute Au atoms initially dissolved in glassy alloys and eventually precipitated out of the Pd9Si2 and Pd3Si intermetallics, forming nearly spherical Au nanocrystals. Our TEM results reveal the unique thermal stability and crystallization processes of the PLD-prepared Pd-Au-Si thin films as well as demonstrate a possibility of producing a large quantity of pure nanocrystals out of amorphous solids for various applications.

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high recurrence or distant metastases rate and the prognosis is challenging. There is mounting evidence that tumor-infiltrating B cells (TIL-Bs) have a crucial, synergistic role in tumor control. However, little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade. Using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, the study identified distinct gene expression patterns in TIL-Bs. HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering. This classification was further validated with TCGA HNSCC data, correlating with patient prognosis, immune cell infiltration, and response to immunotherapy. We found that the B cells activation group exhibited a better prognosis, higher immune cell infiltration, and distinct immune checkpoint levels, including elevated PD-L1. A prognostic model was also developed and validated, highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients. Overall, this study provides a foundational approach for B cells-based tumor classification in HNSCC, offering insights into targeted treatment and immunotherapy strategies.

Structure optimizing of flavonoids against both MRSA and VRE.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.

Three types of enzymes complete the furanocoumarins core skeleton biosynthesis in Angelica sinensis.

Furanocoumarins (FCs) are widely distributed secondary metabolites found in higher plants, including Apiaceae, Rutaceae, Moraceae, and Fabaceae. They play a crucial role in the physiological functions of plants and are well-known for their diverse pharmacological activities. As a representative plant of the Apiaceae family, Angelica sinensis is highly valued for its medicinal properties and FCs are one of the main ingredients of A. sinensis. However, the biosynthetic mechanism of FCs in A. sinensis remains poorly understood. In this study, we successfully cloned and verified three types of enzymes using genome analysis and in vitro functional verification, which complete the biosynthesis of the FCs core skeleton in A. sinensis. It includes a p-coumaroyl CoA 2'-hydroxylase (AsC2'H) responsible for umbelliferone formation, two UbiA prenyltransferases (AsPT1 and AsPT2) that convert umbelliferone to demethylsuberosin (DMS) and osthenol, respectively, and two CYP736 subfamily cyclases (AsDC and AsOD) that catalyze the formation of FCs core skeleton. Interestingly, AsOD was demonstrated to be a bifunctional cyclase and could catalyze both DMS and osthenol, but had a higher affinity to osthenol. The characterization of these enzymes elucidates the molecular mechanism of FCs biosynthesis, providing new insights and technologies for understanding the diverse origins of FCs biosynthesis.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Quantifying the Individual and Combined Effects of Short-Term Heat Stress at Booting and Flowering Stages on Nonstructural Carbohydrates Remobilization in Rice.

Rice production is threatened by climate change, particularly heat stress (HS). Nonstructural carbohydrates (NSCs) remobilization is a key physiological mechanism that allows rice plants to cope with HS. To investigate the impact of short-term HS on the remobilization of nonstructural carbohydrates (NSCs) in rice, two cultivars (Huaidao-5 and Wuyunjing-24) were subjected to varying temperature regimes: 32/22/27 °C as the control treatment, alongside 40/30/35 °C and 44/34/39 °C, for durations of 2 and 4 days during the booting, flowering, and combined stages (booting + flowering) within phytotrons across the years 2016 and 2017. The findings revealed that the stem's NSC concentration increased, while the panicle's NSCs concentration, the efficiency of NSCs translocation from the stem, and the stem NSC contribution to grain yield exhibited a consistent decline. Additionally, sugar and starch concentrations increased in leaves and stems during late grain filling and maturity stages, while in panicles, the starch concentration decreased and sugar concentration increased. The heat-tolerant cultivar, Wuyunjing-24, exhibited higher panicle NSC accumulation under HS than the heat-sensitive cultivar, Huaidao-5, which had more stem NSC accumulation. The flowering stage was the most vulnerable to HS, followed by the combined and booting stages. Heat degree days (HDDs) were utilized to quantify the effects of HS on NSC accumulation and translocation, revealing that the flowering stage was the most affected. These findings suggest that severe HS makes the stem the primary carbohydrate storage sink, and alleviation under combined HS aids in evaluating NSC accumulation, benefiting breeders in developing heat-tolerant rice varieties.

Knowledge, attitude, and practice of atrial fibrillation in high altitude areas.

Background: To investigate the knowledge, attitude, and practice (KAP) of atrial fibrillation (AF) among the general population in high-altitude areas. Methodology: A web-based cross-sectional study was conducted among the general population in high-altitude areas. Results: A total of 786 valid questionnaires were enrolled, with a mean age of 34.75 ± 14.16 years. The mean score of knowledge, attitude and practice were 8.22 ± 6.50 (possible range: 0-10), 28.90 ± 5.63 (possible range: 8-40), 34.34 ± 6.44 (possible range: 9-45), respectively. The multivariate analysis showed that knowledge scores (OR = 1.108, 95% CI = 1.075-1.142, p < 0.001), attitude scores (OR = 1.118, 95% CI = 1.081-1.156, p < 0.001), and never smoking (OR = 2.438, 95% CI = 1.426-4.167, p = 0.001) were independently associated with proactive practice. The structural equation modeling (SEM) showed direct effect of knowledge on practice (p = 0.014), and attitude on practice (p = 0.004), while no effect of knowledge on attitude (p = 0.190). Conclusion: The general population in high-altitude regions had adequate knowledge, positive attitude, and proactive practice towards AF. The SEM was suitable for explaining general population' KAP regarding AF, revealing that knowledge directly and positively affected attitude and practice.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Features Associated with Visible Lamina Cribrosa Pores in Individuals of African Ancestry with Glaucoma: Primary Open-Angle African Ancestry Glaucoma Genetics (POAAGG) Study.

There are scarce data regarding the rate of the occurrence of primary open-angle glaucoma (POAG) and visible lamina cribrosa pores (LCPs) in the eyes of individuals with African ancestry; the potential impact of these features on disease burden remains unknown. We recruited subjects with POAG to the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Through regression models, we evaluated the association between the presence of LCPs and various phenotypic features. In a multivariable analysis of 1187 glaucomatous eyes, LCPs were found to be more likely to be present in eyes with cup-to-disc ratios (CDR) of ≥0.9 (adjusted risk ratio (aRR) 1.11, 95%CI: 1.04-1.19, p = 0.005), eyes with cylindrical-shaped (aRR 1.22, 95%CI: 1.11-1.33) and bean pot (aRR 1.24, 95%CI: 1.13-1.36) cups versus conical cups (p < 0.0001), moderate cup depth (aRR 1.24, 95%CI: 1.06-1.46) and deep cups (aRR 1.27, 95%CI: 1.07-1.50) compared to shallow cups (p = 0.01), and the nasalization of central retinal vessels (aRR 1.33, 95%CI: 1.23-1.44), p < 0.0001). Eyes with LCPs were more likely to have a higher degree of African ancestry (q0), determined by means of SNP analysis (aRR 0.96, 95%CI: 0.93-0.99, p = 0.005 for per 0.1 increase in q0). Our large cohort of POAG cases of people with African ancestry showed that LCPs may be an important risk factor in identifying severe disease, potentially warranting closer monitoring by physicians.

[Identification of Osteoarthritis Inflamm-Aging Biomarkers by Integrating Bioinformatic Analysis and Machine Learning Strategies and the Clinical Validation]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­–ç•¥è¯†åˆ«éª¨å ³èŠ‚ç‚Žç‚Žæ€§è¡°è€ç”Ÿç‰©æ ‡å¿—ç‰©ä¸Žä¸´åºŠéªŒè¯.

Objective: To identify inflamm-aging related biomarkers in osteoarthritis (OA). Methods: Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Results: A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1ß levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1ß, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model. Conclusion: FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.