Histopathological Prognostic Factors of Surgically Treated HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is rising in prevalence and is associated with better survival than HPV-negative OPSCC. In surgically treated HPV-negative OPSCCs, adverse pathologic features such as positive surgical margins, extra-nodal extension (ENE) and perineural invasion are well described to portend worse clinical outcomes. These adverse pathological features, however, are not validated prognostic markers among surgically treated HPV-positive OPSCCs. To that end, we pooled all available evidence to address the prognostic significance of these histologic features. PATIENTS AND METHODS: This meta-analysis was performed according to PRISMA guidelines. PubMed, Web of Science and Embase databases were systematically searched for articles evaluating 13 known adverse histopathological prognostic factors of surgically treated HPV-associated OPSCC. Data analysis was done using R v4.0.5. RESULTS: A total of 32 studies (n = 31,535) fulfilled the inclusion criteria. ENE and advanced pT stage were associated with poorer overall survival (OS) [hazard ratio (HR):1.80, 95% confidence interval (CI) [1.59-2.03], p < 0.0001, HR: 3.28, 95% CI [2.20-4.87], p = 0.0025]; disease-specific survival (DSS) (HR: 3.14, 95% CI [1.20-8.26], p = 0.0327, HR: 3.49, 95% CI [2.45-4.96], p = 0.0043) and disease-free survival (DFS) (HR: 2.03, 95% CI [1.05-3.94], p = 0.0397, HR: 3.66, 95% CI [2.81-4.77], p = 0.0001) respectively. The presence of lymphovascular invasion (HR: 1.46, 95% CI [1.22-1.75], p = 0.0018) and positive margins (HR: 1.50, 95% CI [1.185-1.899], p = 0.0069) significantly worsen OS. CONCLUSION: ENE, advanced pT stage, positive margins and lymphovascular invasion were adverse histologic prognostic marker among surgically treated HPV-positive OPSCC. The presence of these factors should be carefully evaluated in order to select the optimal patients for surgical treatment.

A rare prenylated isoflavone-quinone from the roots of Flemingia philippinensis.

In order to make more rational use of Flemingia Philippinensis, a systematic separation from the roots of F. philippinensis was performed in the current study. The investigation of chemical constituents resulted in the isolation of a rare prenylated isoflavone-quinone, fleminquinone A (1), together with four known analogues (2-5). Their structures were established by extensive physical and spectroscopic data analysis. Anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide induced mouse mononuclear macrophage leukemia cells RAW 264.7 model. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2. Compound 1 also significantly affected the levels of inflammatory cytokines.

Impacts of shellfish and macroalgae mariculture on the seawater carbonate system and air-sea CO2 flux in Haizhou Bay, China.

China is the largest mariculture country, and shellfish and algae output ranks first, showing high carbon sink capacity. In recent years, the single cultivation of macroalgae (Pyropia yezoensis) has been changed to macroalgae-shellfish mariculture in Haizhou Bay to increase the yield of P. yezoensis and improve the water environment quality. In this study, four surveys were carried out in July 2022 during the monoculture period of oyster (Magallana gigas), as well as at different stages of P. yezoensis culture (head-crop period, November 2022, peak growing season, January 2023, and end of harvesting, March 2023) in the mariculture and the surrounding waters of Haizhou Bay. The effects of different stages of culture on the seawater environment and seasonal and spatial variations in the carbonate system were analyzed, and the carbon sink capacity was preliminarily estimated. The results showed that in summer, the calcification of M. gigas and the primary production process of phytoplankton effectively reduced the dissolved inorganic carbon (DIC) level in the culture area. The culture area acts as a CO2 sink, with an average air-sea CO2 flux of -4.5 mmol m-2 d-1. During the polyculture period, the P. yezoensis culture activities maintained the stability of the seawater carbonate system, and the culture area shows strong CO2 sinks, with the average air-sea CO2 flux of -24.10 mmol m-2 d-1, -37.68 mmol m-2 d-1, and -38.99 mmol m-2 d-1, respectively. The absorption of CO2 by large-scale cultured P. yezoensis through the "biological pump" effect is the main factor affecting the CO2 exchange process at the air-sea interface, and the absorption rate of CO2 by P. yezoensis at the mature stage is higher than that at the growth stage before harvesting. The study revealed that macroalgae-shellfish mariculture could promote mutual growth, alleviate environmental pressure, and enhance the carbon sink of the culture area. The relationship between mariculture and the carbon cycle of a mariculture ecosystem is very complicated, and its biochemical process should be given great attention for further study.

Melatonin decreases excessive polyspermy for single oocyte in pigs through the MT2 receptor.

Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P < 0.05). However, these promotional effects were counteracted by melatonin antagonists, suggesting that melatonin enhances cytoplasmic maturation through its receptors in porcine oocytes. Melatonin supplementation also significantly improved the rate of diploid and blastocyst formation after IVF by promoting the normal distribution of cortical granules (P < 0.05). In conclusion, melatonin supplementation during in vitro maturation of porcine oocyte improves fertilization efficiency and embryonic developmental competence by enhancing cytoplasmic maturation.

Cardiac macrophages in maintaining heart homeostasis and regulating ventricular remodeling of heart diseases.

Macrophages are most important immune cell population in the heart. Cardiac macrophages have broad-spectrum and heterogeneity, with two extreme polarization phenotypes: M1 pro-inflammatory macrophages (CCR2-ly6Chi) and M2 anti-inflammatory macrophages (CCR2-ly6Clo). Cardiac macrophages can reshape their polarization states or phenotypes to adapt to their surrounding microenvironment by altering metabolic reprogramming. The phenotypes and polarization states of cardiac macrophages can be defined by specific signature markers on the cell surface, including tumor necrosis factor α, interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), C-C chemokine receptor type (CCR)2, IL-4 and arginase (Arg)1, among them, CCR2+/- is one of most important markers which is used to distinguish between resident and non-resident cardiac macrophage as well as macrophage polarization states. Dedicated balance between M1 and M2 cardiac macrophages are crucial for maintaining heart development and cardiac functional and electric homeostasis, and imbalance between macrophage phenotypes may result in heart ventricular remodeling and various heart diseases. The therapy aiming at specific target on macrophage phenotype is a promising strategy for treatment of heart diseases. In this article, we comprehensively review cardiac macrophage phenotype, metabolic reprogramming, and their role in maintaining heart health and mediating ventricular remodeling and potential therapeutic strategy in heart diseases.

Talaroterpenoids A-F: Six New Seco-Terpenoids from the Marine-Derived Fungus Talaromyces aurantiacus.

Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A-C (1-3), and three meroterpenoids containing an orthoester group, talaroterpenoids D-F (6-8), together with five known compounds (4-5 and 9-11), were isolated from the marine-derived fungus Talaromyces aurantiacus. Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J-based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20-γ-lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC50 values of 11.47 and 11.32 µM, respectively. Talaroterpenoid C (3) showed moderate antifungal activity against A. alternata and P. theae Steyaert.

Activation of the γ-secretase/NICD-PXR/Notch pathway induces Taxol resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is currently the only subtype lacking efficient targeted therapies. Taxol is the primary chemotherapeutic agent for TNBC. However, Taxol resistance often develops in the treatment of TNBC patients, which importantly contributes to high mortality and poor prognosis in TNBC patients. Recent preclinical studies have shown that the inhibition of Notch pathway by γ-secretase inhibitors can slow down the progression of TNBC. Our studies in bioinformatic analysis of breast cancer patients and TNBC/Taxol cells in vitro showed that there was high correlation between the activation of Notch pathway and Taxol resistance in TNBC. Increased γ-secretase activity (by the overexpression of catalytic core PSEN-1) significantly reduced Taxol sensitivity of TNBC cells, and enhanced biological characteristics of malignancy in vitro, and tumour growth in vivo. Mechanistically, increased γ-secretase activity led to the accumulation of NICD in the nucleus, promoting the interaction between NICD and PXR to activate PXR, which triggered the transcription of PXR downstream associated drug resistance genes. Furthermore, we showed that pharmacological inhibition of γ-secretase with γ-secretase inhibitors (Nirogacestat and DAPT) can reverse Taxol resistance in vivo and in vitro. Our results for the first time demonstrate that the activation of γ -secretase/NCD-PXR/Notch pathway is one of important mechanisms to cause Taxol resistance in TNBC, and the blockades of this pathway may represent a new therapeutic strategy for overcoming Taxol resistance in TNBC.

Effectiveness of Audit & Feedback and Academic Detailing Interventions to Support Safer Opioid-prescribing in Primary Care.

BACKGROUND: Opioids, prescribed to manage pain, are associated with safety risks. Quality improvement strategies such as audit and feedback and academic detailing may improve prescribing in primary care. METHODS: We used a matched-cohort design with claims databases. Participants were family physicians practicing in Ontario, Canada. The interventions were a voluntary audit and feedback report with or without academic detailing sessions. Physicians in the control group received neither intervention. The primary outcome was mean rate of high-risk opioid prescriptions per 100 patients per month. Data were analyzed comparing monthly percentage change in slope over 12 months before and 18 months after the intervention. Additional analyses considered only the subgroup of higher-prescribing physicians. RESULTS: There were 1469 (25%) physicians in the audit and feedback group, 245 (4%) in the audit and feedback + academic detailing group, and 4211 (71%) matched controls. All groups showed a significant pre-intervention decline in opioid prescribing. There were no significant between-group differences in opioid-prescribing post-intervention. Among high-prescribing physicians, there was a significant reduction in the audit and feedback group (% change in slope = -0.37, 95%CI = -0.65 to -0.09, p < 0.01), but not in the academic detailing group (% change in slope = 0.19, 95%CI = -0.52 to 0.91, p = .59). CONCLUSION: This study demonstrated declining secular trends in prescribing and suggests that two large-scale initiatives had limited additional benefits. We found some additional reductions after audit and feedback among the highest-volume opioid prescribers. Future interventions should focus on these physicians for the greatest benefit.

One-step copper deposition-induced signal amplification for multiplex bacterial infection diagnosis on a lateral flow immunoassay device.

The lateral flow immunoassay (LFIA) is predominant in rapid diagnostic tests owing to its cost-effectiveness and operational simplicity. However, the conventional LFIA exhibits limited sensitivity and is susceptible to human variance for the result readout, impacting result interpretation. In this study, we introduced a novel one-step copper deposition-induced signal amplification lateral flow immunoassay (osa-LFIA) that markedly enhances the detection sensitivity for Staphylococcus aureus (protein A) and Pseudomonas aeruginosa (exotoxin A). Utilizing gold nanoparticles (AuNPs) as a catalyst, this approach employs ascorbic acid to reduce Cu2+ to Cu0, depositing on AuNPs at the test line and amplifying the signal. A user-friendly design features a three-dimensional paper structure incorporating pre-dried reagents, enabling a streamlined, efficient testing process. The osa-LFIA significantly lowers detection limits to 3 ng mL-1 for protein A and 10 ng mL-1 for exotoxin A, offering a tenfold improvement over conventional LFIA. Additionally, we developed a portable grayscale detection device, achieving less than 10% error in quantitative analysis compared to the data acquired and analyzed in the lab. This entire process, from detection to signal amplification, is completed in just 20 min. For the clinical trial, we utilized the osa-LFIA to test synovial fluid samples infected with Staphylococcus aureus. We also successfully detected different concentrations of the exotoxin A in parallel, with a recovery value of 96%-110%. Our findings demonstrate the osa-LFIA's potential as a rapid, highly sensitive, and simple-to-use diagnostic tool for detecting various pathogens, significantly advancing the field of rapid diagnostic testing.

Exposure to secondhand smoke among school-going adolescents in Malaysia: Results from the National Health and Morbidity Survey (NHMS) 2022: Adolescent Health Survey (AHS).

INTRODUCTION: The adverse effects of secondhand smoke (SHS) exposure on health have been well established. Using the NHMS 2002: Adolescent Health Survey (AHS), this study attempts to evaluate the extent and factors associated with SHS exposure among Malaysian school-going adolescents. METHODS: We conducted the NHMS 2022: AHS to gather a representative sample of school-age teenagers. We employed a cross-sectional study design and a multi-stage sampling procedure. We utilized a pre-validated self-administered questionnaire to collect data from the selected respondents. The data analysis included adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs). Additionally, we investigated the possible two-way interactions between the independent variables. RESULTS: The SHS prevalence was 42.0%. Exposure to secondhand smoke (SHS) was associated with male gender (AOR=1.28; 95 CI: 1.20-1.38), older age (AOR=1.46; 95% CI: 1.33-1.60), Malay (AOR=1.88; 95% CI: 1.49-2.37), Bumiputra Sabah (AOR=2.23; 95% CI: 1.67-2.99), Bumiputra Sarawak (AOR=2.43; 95% CI: 1.80-3.28), and Chinese ethnicity (AOR=2.89; 95 CI: % 2.30-3.64), as well as current smoking (AOR=2.78; 95% CI: 2.50-3.09), having separated or divorced parents (AOR=1.12; 95% CI: 1.02-1.23), and parental tobacco product use (AOR=4.75; 95% CI: 4.44-5.08). We found significant interactions between: 1) Age group with gender and ethnicity; 2) Gender and ethnicity; and 3) Parental smoking status with gender, response to tobacco use, parents' marital status, and ethnicity. CONCLUSIONS: Parental characteristics, sociodemographic characteristics, and SHS exposure are strongly correlated. In addition, there is evidence of smoking displacement to the house from other areas by parents/guardians. This study offers a fresh perspective on how these variables influence the likelihood of SHS exposure for Malaysian school-age teenagers. More efforts should focus on parental variables and sociodemographic traits, especially parental smoking cessation support.

Microbial coadaptation drives the dynamic stability of microecology in mainstream and sidestream anammox systems under exposure of progesterone.

Microbial cooperation determines the efficacy of wastewater biological treatment, and the adaptability of microorganisms to environmental stresses varies. Recently, extensive use of hormones results in their inevitable discharge into aquatic environment. Therefore, mainstream and sidestream anammox reactors were constructed in this study to evaluate their removal performance of progesterone and nitrogen simultaneously, the adaptability of anammox consortia to progesterone stress and the corresponding regulation mechanism. Both anammox processes had the resilience to progesterone stress, with the average nitrogen removal efficiency exceeding 90 %. At the same time, progesterone removal efficiency also exceeded 70 %. In contrast, microbial community in the mainstream reactors was more susceptible to progesterone interference. The adaptation of anammox consortia mainly depended on microbial cooperation and molecular regulation. Initially, bacteria secreted more extracellular polymeric substances to detain progesterone. Biodegradation also contributed to mitigating the side effect of progesterone, which was demonstrated by the proliferation of potential degrading bacteria such as Bacillus salacetis, Bacillus wiedmannii and Rhodococcus erythropolis. In addition, the enhancement of microbial interaction intensity drove their cooperation to enhance adaptability and maintain stable performance. Combined with metagenomic and metatranscriptomic analyses, such microbial adaptability was enhanced through molecular regulations, including the energy redistribution for amino acid synthesis and alteration of key metabolic pathways. Related functional gene expressions and microbial interactions were, in turn, regulated by quorum sensing. This work verifies the feasibility of anammox process in hormone-containing wastewater treatment and provides a holistic understanding of molecular mechanism of microbial interaction and coadaptation to stress.

Job Stress Can Lead to Intestinal Inflammation and Subsequent Gut-Originated Extraoral Halitosis.

OBJECTIVES: Reports on stress-associated halitosis are scarce and have only focused on intraoral halitosis. This work aimed to study stress-associated extraoral halitosis (EOH) and further investigate its potential association with stress-induced intestinal inflammation. METHODS: This retrospective study included 664 white-collar employees with self-reported stress-associated halitosis. They underwent the organoleptic score (OLS) to assess halitosis, modified Brief Job Stress Questionnaire (BJSQ) score to assess job stress, OralChroma breath test to measure volatile sulfur compounds (VSCs) in breath, and hydrogen/methane breath test (HMBT) and nitric oxide breath test (NOBT) to detect intestinal inflammation. They were classified into high-stress and low-stress groups based on their modified BJSQ score. RESULTS: Totally, 106 eligible patients were identified as having stress-associated EOH, and 61 of them had high stress. Additionally, 70 (66.04%) and 73 (68.87%) of them tested positive for HMB and NOBT, respectively. Dimethyl sulfide (DMS) was found to be the predominant VSC in breath. High-stress patients had significantly higher positivity rates for HMBT and NOBT, OLS, and exhaled DMS levels compared to low-stress patients. HMBT-positive patients and NOBT-positive patients had significantly higher OLS and exhaled DMS levels compared to their respective negative counterparts. CONCLUSIONS: Job stress can lead to intestinal inflammation and subsequent gut-originated EOH.

Impact of mini-dose dexmedetomidine supplemented analgesia on sleep structure in patients at high risk of obstructive sleep apnea: a pilot trial.

Background: Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. Objectives: To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. Design: A pilot randomized, double-blind, placebo-controlled trial. Setting: A tertiary university hospital in Beijing, China. Patients: One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. Intervention: After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 µg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night. Main outcome measures: Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better). Results: All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups. Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. Clinical trial registration: Clinicaltrials.gov, identifier NCT04608331.

The rheumatoid arthritis gut microbial biobank reveals core microbial species that associate and effect on host inflammation and autoimmune responses.

Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture-independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA-originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium- and high-abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL-10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS-treated and not DSS-treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL-10 and increased IL-17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.

GHRH and its analogues in central nervous system diseases.

Growth hormone-releasing hormone (GHRH) is primarily produced by the hypothalamus and stimulates the release of growth hormone (GH) in the anterior pituitary gland, which subsequently regulates the production of hepatic insulin-like growth factor-1 (IGF-1). GH and IGF-1 have potent effects on promoting cell proliferation, inhibiting cell apoptosis, as well as regulating cell metabolism. In central nerve system (CNS), GHRH/GH/IGF-1 promote brain development and growth, stimulate neuronal proliferation, and regulate neurotransmitter release, thereby participating in the regulation of various CNS physiological activities. In addition to hypothalamus-pituitary gland, GHRH and GHRH receptor (GHRH-R) are also expressed in other brain cells or tissues, such as endogenous neural stem cells (NSCs) and tumor cells. Alternations in GHRH/GH/IGF-1 axis are associated with various CNS diseases, for example, Alzheimer's disease, amyotrophic lateral sclerosis and emotional disorders manifest GHRH, GH or IGF-1 deficiency, and GH or IGF-1 supplementation exerts beneficial therapeutic effects on these diseases. CNS tumors, such as glioma, can express GHRH and GHRH-R, and activating this signaling pathway promotes tumor cell growth. The synthesized GHRH antagonists have shown to inhibit glioma cell growth and may hold promising as an adjuvant therapy for treating glioma. In addition, we have shown that GHRH agonist MR-409 can improve neurological sequelae after ischemic stroke by activating extrapituitary GHRH-R signaling and promoting endogenous NSCs-derived neuronal regeneration. This article reviews the involvement of GHRH/GH/IGF-1 in CNS diseases, and potential roles of GHRH agonists and antagonists in treating CNS diseases.

[Serological and Molecular Biological Analysis of Rare Cases of p-Blood Type].

OBJECTIVE: To clarify the specificity of patient blood type and blood type antibody through patient blood type serological tests and molecular biology results, and to search for matching blood for patients. METHODS: Blood type serological methods were used for the identification of red blood cell ABO, RhD, and p blood type. Salt water method, microcolumn gel method and IAT method were used for irregular antibody screening and antibody specificity identification. Forward and reverse sanger sequencing was used to amplify specifically the third exon (CDS sequence) of the A4GALT gene, identify the mutation site and genotype of the gene. RESULTS: The patient's serological blood type was positive for type B and D, indicating a p phenotype. At the same time, anti-Tja was detected in the serum, and further sequencing of the A4GALT gene exon was performed, the homozygous mutation with G>C occurred at base 559, and the genotype ISBT was named A4GALT*01N.10. Molecular biology verification confirmed it to be p blood group. Serological methods confirm that the patient's serum contains anti-Tja. CONCLUSION: The joint identification of the rare blood type-p blood type by serological and molecular biological methods is of great significance for safe clinical blood transfusion.

A Dual-Branch Cross-Modality-Attention Network for Thyroid Nodule Diagnosis Based on Ultrasound Images and Contrast-Enhanced Ultrasound Videos.

Contrast-enhanced ultrasound (CEUS) has been extensively employed as an imaging modality in thyroid nodule diagnosis due to its capacity to visualise the distribution and circulation of micro-vessels in organs and lesions in a non-invasive manner. However, current CEUS-based thyroid nodule diagnosis methods suffered from: 1) the blurred spatial boundaries between nodules and other anatomies in CEUS videos, and 2) the insufficient representations of the local structural information of nodule tissues by the features extracted only from CEUS videos. In this paper, we propose a novel dual-branch network with a cross-modality-attention mechanism for thyroid nodule diagnosis by integrating the information from tow related modalities, i.e., CEUS videos and ultrasound image. The mechanism has two parts: US-attention-from-CEUS transformer (UAC-T) and CEUS-attention-from-US transformer (CAU-T). As such, this network imitates the manner of human radiologists by decomposing the diagnosis into two correlated tasks: 1) the spatio-temporal features extracted from CEUS are hierarchically embedded into the spatial features extracted from US with UAC-T for the nodule segmentation; 2) the US spatial features are used to guide the extraction of the CEUS spatio-temporal features with CAU-T for the nodule classification. The two tasks are intertwined in the dual-branch end-to-end network and optimized with the multi-task learning (MTL) strategy. The proposed method is evaluated on our collected thyroid US-CEUS dataset. Experimental results show that our method achieves the classification accuracy of 86.92%, specificity of 66.41%, and sensitivity of 97.01%, outperforming the state-of-the-art methods. As a general contribution in the field of multi-modality diagnosis of diseases, the proposed method has provided an effective way to combine static information with its related dynamic information, improving the quality of deep learning based diagnosis with an additional benefit of explainability.

Impact of emergence delirium on long-term survival in older patients after major noncardiac surgery: A longitudinal prospective observational study.

STUDY OBJECTIVE: To test the hypothesis that emergence delirium might be associated with worse long-term survival. DESIGN: A longitudinal prospective observational study. SETTING: A tertiary hospital in Beijing, China. PATIENTS: A total of 942 patients aged 65-90 years who were admitted to post-anesthesia care unit (PACU) after major noncardiac surgery under general anesthesia. EXPOSURES: Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. MEASUREMENTS: Patients were followed up once a year for at least 3 years. Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. Associations between emergence delirium and long-term survivals were analyzed with the Cox proportional hazard models. MAIN RESULTS: Among enrolled patients, 915 completed perioperative assessments; 906 completed long-term follow-up (mean age 72 years; 60 % [545/906] male; 73 % [660/906] cancer surgery). At the end of follow-up (median 43 months), there were 69 deaths in 331 patients (21 %) with emergence delirium versus 114 deaths in 575 patients (20 %) without: unadjusted hazard ratio 1.10 (95 % CI: 0.81 to 1.48); P = 0.547; adjusted hazard ratio 0.96 (95 % CI: 0.70 to 1.32); P = 0.797. Recurrence-free survival was 73/331 (22 %) in patients with emergence delirium versus 121/575 (21 %) without: unadjusted hazard ratio 1.08 (95 % CI: 0.81 to 1.45); P = 0.598; adjusted hazard ratio 0.94 (95 % CI: 0.69 to 1.28); P = 0.695. Event-free survival was 159/331 (48 %) in patients with emergence delirium versus 268/575 (47 %) without: unadjusted hazard ratio 1.06 (95 % CI: 0.87 to 1.29); P = 0.563; adjusted hazard ratio 0.98 (95 % CI: 0.80 to 1.21); P = 0.875. CONCLUSIONS: We did not find significant association between emergence delirium and worse long-term survival in older patients after general anesthesia and major surgery mainly for cancer. The effects of emergence delirium on long-term outcomes deserve further investigation. CLINICAL TRIAL REGISTRATIONS: www.chictr.org.cn; ChiCTR-OOC-17012734.

Design, synthesis and biological evaluation of novel benzimidazole-derived p21-activited kinase 4 (PAK4) inhibitors bearing a 4-(4-methylpiperazin-1-yl)phenyl scaffold as potential antitumor agents.

A series of novel 6-(4-(4-methylpiperazin-1-yl)phenyl)-1H-benzo[d]imidazole-based p21-activited kinase 4 (PAK4) inhibitors were designed and synthesized based on the structure of lead compound GNE-2861 and that of anticancer inhibitors reported in our previous studies. All target compounds so designed were preliminarily screened in vitro for anti-tumor potency through kinase inhibitory assays and MTT assays, which revealed that most compounds exhibited significant inhibitory effects on PAK4 enzyme as well as prominent antiproliferative activities against four cancer cell models (A549, NCI-H1975, MDA-MB-231 and SK-BR-3) and low damage to healthy cells. In particular, the hit compound 12i was identified as the most effective and rather selective compound both at the enzyme and cellular level. Meanwhile, molecular docking and dynamic studies disclosed that compound 12i could bind to PAK4 stably via multiple interactions applied between the compound and the enzyme. Further mechanism studies indicated that compound 12i could inhibit the proliferation and suppress the migratory potential of MDA-MB-231 cells by inhibiting the phosphorylation of PAK4 and LIMK1, arresting cell cycle in the G0/G1 phase, inducing apoptosis and promoting ROS production. Notably, compound 12i could effectively inhibit triple-negative breast cancer (TNBC) growth with little toxicity in the MDA-MB-231 cell xenograft model. Taken together, in vitro and in vivo results demonstrated that compound 12i possessed high drug potential as an inhibitor of PAK4 to inhibit the growth and metastasis of TNBC.

Bioactive metabolites: a clue to the link between MASLD and CKD?

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules [such as bile acids (BAs), trimethylamine-N-oxide, and short-chain fatty acids], or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.