Mechanism of efferocytosis in atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

[Characterization of Microplastic Surface Bacterial Community Structure and Prediction of Ecological Risk in Poyang Lake, China].

In recent years, the environmental pollution of microplastics in Poyang Lake has received increasing attention. Baisha Lake of Poyang Lake was selected as the study area, and samples of water and sediments of Baisha Lake and the microplastics therein were collected, and the polymer types of microplastics were identified as polyethylene (PE), polyester (PET), polypropylene (PP), and polystyrene (PS) using Fourier infrared spectroscopy. We also analyzed the structural composition of bacterial communities in water, in sediments, and on microplastic surfaces using 16S high-throughput sequencing. The species richness and diversity of bacteria on the microplastic surfaces were lower than those in the surrounding water and sediments. The results of NMDS analysis showed that the bacterial community structures on the microplastic surfaces differed greatly from those in the surrounding sediments and water. The bacterial community composition in water and sediment differed from that on the microplastic surfaces, and the dominant bacterial phyla on the microplastic surfaces were Proteobacteria and Bacteroidota, and their relative abundance on the microplastic surfaces was higher than that in sediment. The relative abundance of Proteobacteria was higher than that in water. The relative abundances of Bacteroidota and Actinobacteriota were significantly lower than that of water. Massilia and Pseudomonas were the dominant genera on the microplastic surfaces, and their relative abundances were significantly higher than those in the surrounding water and sediments. BugBase phenotype prediction revealed that the relative abundance of contains mobile elements, biofilm formation, potential pathogenicity, and stress tolerance phenotypes of microplastic bacterial communities were significantly higher than those of the surrounding water and sediments. The results revealed that microplastics may have contributed to the spread of harmful bacteria, including pathogenic bacteria, and increased the potential pathogenicity of bacterial communities. Additionally, microplastic surface bacterial communities had higher phenotypes of mobile gene element content. Revealing the potential harm of microplastic pollution to wetland ecology at the micro level may provide a scientific reference for maintaining the ecological stability of wetlands.

The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer.

BACKGROUND: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated. METHODS: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays. RESULTS: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells. CONCLUSION: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

The regulatory role and mechanism of mast cells in tumor microenvironment.

Mast cells (MCs) have emerged as pivotal contributors to both the defensive immune response and immunomodulation. They also exhibit regulatory functions in modulating pathological processes across various allergic diseases. The impact of MC presence within tumor tissues has garnered considerable attention, yielding conflicting findings. While some studies propose that MCs within tumor tissues promote tumor initiation and progression, others advocate an opposing perspective. Notably, evidence emphasizes the dual role of MCs in cancer, both as promoters and suppressors, is crucial for optimizing cancer treatment strategies. These conflicting viewpoints have generated substantial controversy, underscoring the need for a comprehensive understanding of MC's role in tumor immune responses.

Prophylactic use of vancomycin powder on postoperative infection after total joint arthroplasty.

OBJECTIVE: By reviewing the literature analyzing vancomycin powder for preventive surgery, the effect of this method on reducing the infection rate after TJA was systematically evaluated to provide a basis for future clinical work. METHODS: Using PubMed, Medline, Elsevier, and CNKI, with the following mesh words: "vancomycin", "local / intraoperative / topical / intrawound", "TJA", "TKA", "THA", "total joint arthroplasty", "total knee arthroplasty", "total hip arthroplasty", "infection", and "SSI", to search for case-control research papers on the impact of prophylactic application of vancomycin powder on the incidence of postoperative infection, we compared the overall infection rate in the literature by using RevMan 5.3 meta-analysis software and analyzed the impact of vancomycin on the infection rate of different parts and types of TJA according to different subgroups. RESULTS: A total of 22 qualified studies were selected; twenty-five studies compared the effect of prophylactic use of vancomycin powder on infection rates after TJA. There were 23,363 cases in total, including 9545 cases in the vancomycin group and 13,818 cases in the control group. The results of the meta-analysis showed that the possibility of postoperative infection after prophylactic use of vancomycin powder was significantly lower than that without vancomycin risk ratio: 0.38 [0.23,0.59], P < 0.01). However, a meta-analysis of randomized controlled trials (RCTs) showed no significant effect of vancomycin on postoperative infection (P = 0.52). CONCLUSION: Based on the retrospective studies, local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection. High-quality RCTs should be carried out to further evaluate these results.

[Effects of Polystyrene Microplastics Combined with Cadmium Contamination on Soil Physicochemical Properties and Physiological Ecology of Lactuca sativa].

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.

Hydrogen sulfide inhibits alveolar type II cell senescence and limits pulmonary fibrosis via promoting MDM2-mediated p53 degradation.

AIM: Senescence of alveolar type II (AT2) cells is an important driver of pulmonary fibrosis. This study aimed to investigate whether and how dysregulation of hydrogen sulfide (H2 S) production affected AT2 cell senescence, and then explored the effect of H2 S on the communication between AT2 and fibroblasts. METHODS: ICR mice were intratracheally administered with bleomycin (3 mg/kg). Sodium hydrosulfide (NaHS, 28 µmol/kg/d) was intraperitoneally injected for 2 weeks. The H2 S-generating enzyme cystathionine-ß-synthase (CBS) knockout heterozygous (CBS+/- ) mice were used as a low H2 S production model. RESULTS: Analysis of microarray datasets revealed downregulation of H2 S-generating enzymes in lung tissues of patients with pulmonary fibrosis. Decreased H2 S production was correlated with higher levels of cell senescence markers p53 and p21 in bleomycin-induced lung fibrosis. CBS+/- mice exhibited increased levels of p53 and p21. The numbers of AT2 cells positive for p53 and p21 were increased in CBS+/- mice as compared to control mice. H2 S donor NaHS attenuated bleomycin-induced AT2 cell senescence both in vivo and in vitro. H2 S donor suppressed bleomycin-induced senescence-associated secretory phenotype (SASP) of AT2 cells via inhibiting p53/p21 pathway, consequently suppressing proliferation and myofibroblast transdifferentiation of fibroblasts. Mechanically, H2 S suppressed p53 expression by enhancing the mouse double-minute 2 homologue (MDM2)-mediated ubiquitination and degradation of p53. CONCLUSION: H2 S inactivated p53-p21 pathway, consequently suppressing AT2 cell senescence as well as cell communication between senescent AT2 cells and fibroblasts. Aberrant H2 S synthesis may contribute to the development of pulmonary fibrosis through promoting the activation loop involving senescent AT2 cells and activated fibroblasts.

The associations of secondhand smoke exposure with neurodevelopmental disorders and critical time window identification: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure was harmful for brain development. However, the association between SHS exposure and NDDs diagnosis were unclear. OBJECTIVES: To evaluate associations between SHS exposure and NDDs diagnosis, identify critical time windows, and summarize the strength of evidence. METHODS: To investigate the associations of SHS exposure and the development of NDDs, we searched Ovid, EMBASE, Web of Science, Cochrane Library, and PubMed for all the relevant studies up to 31 March 2023. The risk estimates and standardized mean differences (SMD) for the individuals with any NDDs who were exposed to SHS exposure compared with those unexposed or low-exposed. RESULTS: The results showed that a total of 31,098 citations were identified, of which 54 studies were included. We identified significant associations between SHS exposure and the risks of NDDs including specific types of NDDs like attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) despite the observed heterogeneity for NDDs and ADHD. We also observed a significant association between cotinine exposure and ADHD. However, inconsistent ratings between the two quality-of-evidence methods for all the meta-analyses indicated the current evidence of the associations and the potential exposure window remained inconclusive. DISCUSSION: Our findings suggested that SHS exposure was associated with a higher risk of developing ADHD and LD, with inconclusive quality-of-evidence. In addition, period-specific associations remained unclear based on current evidence.

Prediction of Lumbar Pedicle Screw Loosening Using Hounsfield Units in Computed Tomography

INTRODUCTION: One of the most common issues following pedicle screw fixation is pedicle screw loosening. There are, however, few trustworthy methods for predicting screw loosening. The goal of the current study was to identify an efficient technique for using preoperative CT scanning to predict screw loosening in older patients and to offer recommendations for preoperative surgical planning. METHODS: The current analysis included retrospectively all patients who underwent lumbar pedicle screw fixation for degenerative lumbar diseases in our department between January 2015 and January 2022. Hounsfield units were used to assess each vertebra's attenuation in a CT scan (HU). Postoperative X-ray testing identified screw loosening. Using IBMSPSS 24.00 software, one-way analysis of variance (ANOVA) and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Over a mean follow-up period of 28.4±11.5 (range 12-44 months) months, screw loosening was noted in 53 of 242 patients (136 male and 106 female, average age 58.7±7.3 years). Gender, BMI, smoking habits, and whether or not a patient had diabetes or spondylolisthesis were not shown to be significantly different among the patients (P>0.05). The difference between the average lumbar vertebral HU values in the screw-loosening group and the control group was significant (P<0.01) at 120.3±31.5HU and 138.6±37.6HU, respectively. The average HU value of L1-L4 exhibited an area under the curve (AUC) of 0.691 (95% CI: 0.614-0.784), according to ROC curve analysis. A HU cut-off value of 122 HU is a likely cut-off point to predict screw loosening with a sensitivity of 70% and a specificity of 58%. CONCLUSION: The use of screw augmentation techniques can be decided using a prospective CT scan HU value-based prediction. An independent risk factor for screw loosening in an instrumented lumbar vertebra is a cutoff L1-L5 average HU value of 122 HU.

Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor.

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.

Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I.

Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 µM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.

Small-molecule exhibits anti-tumor activity by targeting the RNA m6A reader IGF2BP3 in ovarian cancer.

Based on its absence in normal tissues and its role in tumorigenesis and tumor progression, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of N6-methyladenosine (M6A) on RNA, represents a putative valuable and specific target for some cancer therapy. In this study, we performed bioinformatic analysis and immunohistochemistry (IHC) to find that IGF2BP3 was highly expressed in tumor epithelial cells and fibroblasts of ovarian cancer (OC), and was associated with poor prognosis, metastasis, and chemosensitivity in OC patients. In particular, we discovered that knockdown IGF2BP3 expression inhibited the malignant phenotype of OC cell lines by decreasing the protein levels of c-MYC, VEGF, CDK2, CDK6, and STAT1. To explore the feasibility of IGF2BP3 as a therapeutic target for OC, a small molecular AE-848 was designed and screened by molecular operating environment (MOE), which not only could duplicate the above results of knockdown assay but also reduced the expression of c-MYC in M2 macrophages and tumor-associated macrophages and promoted the cytokine IFN-γ and TNF-α secretion. The pharmacodynamic models of two kinds of OC bearing animals were suggested that systemic therapy with AE-848 significantly inhibited tumor growth by reducing the expression of tumor-associated antigen (c-MYC/VEGF/Ki67/CDK2) and improving the anti-tumor effect of macrophages. These results suggest that AE-848 can inhibit the growth and progression of OC cells by disrupting the stability of the targeted mRNAs of IGF2BP3 and may be a targeted drug for OC treatment.

The prevalence of HPV among 164,137 women in China exhibited some unique epidemiological characteristics.

OBJECTIVE: The persistence of HPV infection is a significant etiological factor in the development of cervical cancer. The present study investigated the prevalence and genotype distribution of human papillomavirus (HPV) in a cohort of 164,137 unvaccinated women from Wenzhou, aiming to provide guidance for clinics in the cervical cancer screening and HPV vaccination strategies. METHODS: The present retrospective study included a total of 164,137 women, comprising 118,484 outpatients and 45,653 healthy female subjects recruited from 2015 to 2020. Cervical exfoliated cells were collected from these participants for subsequent DNA extraction. The extracted DNA samples were underwent analysis using a fluorescence in situ hybridization method, encompassing the detection of 27 HPV genotypes. RESULTS: The overall prevalence of HPV was 17.35%; this corresponded to a prevalence of 19.10% in the outpatient group and 12.82% in the healthy female group. Among the outpatient group, the five most prevalent HPV genotypes were identified as HPV 52, 58, 16, 53, and 61. In the healthy female group, the five most common HPV genotypes were found to be HPV 52, 53, 58, 61, and 81. Additionally, it was estimated that the highest rate of HPV infection occurred among individuals aged between 10 and 19 years old (44.65%) and those aged between 60 and 69 years old (27.35%). CONCLUSIONS: The prevalence of HPV in this region is substantial; therefore, it is imperative to implement scientifically sound and rational clinical interventions such as vaccination. Routine cervical screening should be performed to prevent the development of cervical intraepithelial neoplasia resulting from persistent infection with high-risk HPV, particularly in women with gynecological diseases and those over 60 years old.

Impact of patient characteristics on innate immune responses and inflammasome activation in ex vivo human lung tissues infected with influenza A virus.

Background: Influenza A virus (IAV) infection poses a persistent global health challenge, necessitating a nuanced grasp of host immune responses for optimal interventions. While the interplay between aging, immunosenescence, and IAV is recognized as key in severe lower respiratory tract infections, the role of specific patient attributes in shaping innate immune reactions and inflammasome activity during IAV infection remains under-investigated. In this study, we utilized an ex vivo infection model of human lung tissues with H3N2 IAV to discern relationships among patient demographics, IAV nucleoprotein (NP) expression, toll-like receptor (TLR) profiles, PD-1/PD-L1 markers, and cytokine production. Methods: Our cohort consisted of thirty adult patients who underwent video-assisted thoracoscopic surgery during 2018-2019. Post-surgical lung tissues were exposed to H3N2 IAV for ex vivo infections, and the ensuing immune responses were profiled using flow cytometry. Results: We observed pronounced IAV activity within lung cells, as indicated by marked NP upregulation in both epithelial cells (P = 0.022) and macrophages (P = 0.003) in the IAV-exposed group relative to controls. Notably, interleukin-2 levels correlated with variations in TLR1 expression on epithelial cells and PD-L1 markers on macrophages. Age emerged as a modulating factor, dampening innate immune reactions, as evidenced by reduced interleukin-2 and interferon-γ concentrations (both adjusted P < 0.05). Intriguingly, a subset of participants with pronounced tumor necrosis factor-alpha post-mock infection (Cluster 1) showed attenuated cytokine responses in contrast to their counterparts in Cluster 2 and Cluster 3 (all adjusted P < 0.05). Individuals in Cluster 2, characterized by a low post-mock infection NP expression in macrophages, exhibited reduced variations in both NP and TLR1-3 expressions on these cells and a decreased variation in interleukin-2 secretion in comparison to their Cluster 3 counterparts, who were identified by their elevated NP macrophage expression (all adjusted P < 0.05). Conclusion: Our work elucidates the multifaceted interplay of patient factors, innate immunity, and inflammasome responses in lung tissues subjected to ex vivo H3N2 IAV exposure, reflecting real-world lower respiratory tract infections. While these findings provide a foundation for tailored therapeutic strategies, supplementary studies are requisite for thorough validation and refinement.

Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis.

OBJECTIVE: Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. METHODS: This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. RESULTS: With adjustment for age, a three-class model was identified, with 42.7% of participants classified as "low comorbidity class (cluster 1)", 44.2% as "cardiometabolic multimorbidity class (cluster 2)", and 13.1% as "FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract)." The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708-14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281-1.953; p<0.001) in cluster 3. CONCLUSION: Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

Low-to-Moderate Arsenic Exposure and Urothelial Tract Cancers with a Long Latent Period of Follow-Up in an Arseniasis Area.

BACKGROUND: Arsenic exposure can cause adverse health effects. The effects of long-term low-to-moderate exposure and methylations remain unclear. OBJECTIVE: This study aims to examine the association between low-to-moderate arsenic exposure and urothelial tract cancers while considering the effects of methylation capacity. METHODS: In this study, 5,811 participants were recruited from an arseniasis area in Taiwan for inorganic arsenic metabolite analysis. This follow-up study was conducted between August 1995 and December 2017. We identified 85 urothelial tract cancers in these participants, including 49 bladder and 36 upper urothelial tract cancer cases. A Cox proportional hazards model was employed. RESULTS: The analyses revealed a significant association between concentrations of inorganic arsenic in water > 100 ug/L and bladder cancer occurrence, with a hazard ratio (HR) of 4.88 (95% CI 1.35-17.61). A monotonic trend was observed between concentrations of inorganic arsenic in water (from 0 to > 100 ug/L) and the incidence of urothelial tract cancer, including bladder cancer (p < 0.05) and upper urothelial tract cancers (p < 0.05). Participants with a lower primary methylation index or higher secondary methylation index had a prominent effect. CONCLUSIONS: Rigorous regulations and active interventions should be considered for populations with susceptible characteristics.

Persulfate enhanced removal of bisphenol A by copper oxide/reduced graphene oxide foam: Influencing factors, mechanism and degradation pathway.

The CuO/reduced graphene oxide foam (CuO/RGF) with excellent recyclability was prepared via hydrothermal method followed by freeze drying treatment for bisphenol A (BPA) removal via activating peroxydisulfate (PDS). SEM, XRD, XPS, FT-IR, BET, and TG techniques were used to investigate the structure and property of CuO/RGF. The effect of degradation conditions (pH, PDS amount, Cl-, HCO3-, HA and FA) on BPA removal by CuO/RGF were investigated. The result presented that CuO nanosheet was inserted into the RGF carrier with three-dimensional structure. The degradation rate constant of BPA over CuO/RGF (0.00917 min-1) was 1.24 and 6.46 times higher than those of BPA over CuO (0.00714 min-1) and RGF (0.00142 min-1). More importantly, the pore structure of RGF can successfully limit the release of Cu (II) compared to pure CuO. According to quenching test as well as electron spin resonance (EPR) spectra, BPA degradation was triggered by 1O2, •OH and SO4•-, which was the combination of nonradical (1O2) and radical activation of PDS (•OH and SO4•-). The possible degradation route of BPA was proposed based on intermediates obtained by combining solid phase extraction pretreatment technique with high performance liquid-mass spectrometry. After assessing the viability of MCF-7 cells, we can see that the estrogenic activities of treated solution reduced without producing stronger endocrine disruptors.

[Effect of multi-glycosides of Tripterygium wilfordii on renal injury in diabetic kidney disease rats through NLRP3/caspase-1/GSDMD pyroptosis pathway].

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1ß(IL-1ß) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1ß and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.