Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

A nationwide study on new onset atrial fibrillation risk factors and its association with hospital mortality in sepsis patients.

Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01-1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

HVEM in acute lymphocytic leukemia facilitates tumour immune escape by inhibiting CD8+ T cell function.

PURPOSE: Leukaemia remains a major contributor to global mortality, representing a significant health risk for a substantial number of cancer patients. Despite notable advancements in the field, existing treatments frequently exhibit limited efficacy or recurrence. Here, we explored the potential of abolishing HVEM (herpes virus entry mediator, TNFRSF14) expression in tumours as an effective approach to treat acute lymphoblastic leukaemia (ALL) and prevent its recurrence. METHODS: The clinical correlations between HVEM and leukaemia were revealed by public data analysis. HVEM knockout (KO) murine T cell lymphoblastic leukaemia cell line EL4 were generated using CRISPR-Cas9 technology, and syngeneic subcutaneous tumour models were established to investigate the in vivo function of HVEM. Immunohistochemistry (IHC), RNA-seq and flow cytometry were used to analyse the tumour immune microenvironment (TIME) and tumour draining lymph nodes (dLNs). Immune functions were investigated by depletion of immune subsets in vivo and T cell functional assays in vitro. The HVEM mutant EL4 cell lines were constructed to investigate the functional domain responsible for immune escape. RESULTS: According to public databases, HVEM is highly expressed in patients with ALL and acute myeloid leukemia (AML) and is negatively correlated with patient prognosis. Genetic deletion of HVEM in EL4 cells markedly inhibited tumour progression and prolonged the survival of tumour-bearing mice. Our experiments proved that HVEM exerted its immunosuppressive effect by inhibiting antitumour function of CD8+ T cell through CRD1 domain both in vivo and in vitro. Additionally, we identified a combination therapy capable of completely eradicating ALL tumours, which induces immune memory toward tumour protection. CONCLUSIONS: Our study reveals the potential mechanisms by which HVEM facilitates ALL progression, and highlights HVEM as a promising target for clinical applications in relapsed ALL therapy.

[Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury].

OBJECTIVE: To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assistance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury. METHODS: A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022. Among them, 39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of (44.98±7.33) years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy including 24 males and 13 females with an average age of (44.37±10.82) years old. Among them, 42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation (INFIX) or suprapubic support screws to fix the anterior pelvic ring. Postoperative follow-up time, operation time, complications of the two groups were compared. Results of Matta reduction criteria, Majed efficacy evaluation, the CT grading and the rate of secondary surgical revision were compared. RESULTS: The nailing time of (32.63±7.33) min in CT group was shorter than that of (52.95±10.64) min in C-arm group (t=-9.739, P<0.05). The follow-up time between CT group (11.97±1.86) months and C-arm group (12.03±1.71) months were not statistically significant(P>0.05). The postoperative complication rates between two groups were not statistically significant (χ2=0.159, P>0.05). Results of Matta reduction criteria (Z=2.79, P<0.05), Majeed efficacy evaluation(Z=2.79, P<0.05), CT grading (Z=2.83, P<0.05) in CT group were better than those in C-arm group(P<0.05); the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group (χ2=5.641, P<0.05). CONCLUSION: Compared with traditional C-arm fluoroscopy, intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time, high accuracy and safety, and significant decrease in postoperative secondary revision rate, and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Serum Aspergillus fumigatus-Specific IgG as a Complementary Biomarker in Differentiating Endotypes of Chronic Rhinosinusitis: A Study on Its Role and Diagnostic Efficacy in Type 2 Inflammation.

BACKGROUND: Aspergillus is one of the most common pathogens causing fungal allergy in the respiratory tract. Serum Aspergillus fumigatus-specific immunoglobulin G (Af-sIgG) levels have been used as a biomarker for the diagnosis and treatment response monitoring in airway allergic diseases such as allergic bronchopulmonary aspergillosis and allergic fungal rhinosinusitis. However, its role in common primary chronic rhinosinusitis (CRS) was unclear. OBJECTIVE: This study aims to evaluate whether serum Af-sIgG level could serve as a biomarker for the disease presentation of primary CRS. METHODS: We obtained serum Af-sIgG levels from patients diagnosed as bilateral primary CRS refractory to medical treatment and evaluated the correlations between serum Af-sIgG levels and disease severity in patients with type 2 (T2) and non-T2 CRS. RESULTS: Patients with T2 CRS exhibited significantly higher serum Af-sIgG levels than non-T2 CRS patients. The cut-off value of serum Af-sIgG in T2 CRS was 20.9 mg/L, with an odds ratio of 3.8 (95% CI 1.17-12.20, P = .026). Furthermore, serum Af-sIgG levels were positively correlated with symptom scores evaluated by the Sino-Nasal Outcome Test-22 (SNOT-22) scores in T2 patients (P = .009). While stratified by SNOT-22 total scores, patients with severe disease had higher serum Af-sIgG levels only in T2 CRS (P = .034). In individual domains of SNOT-22 analysis, serum Af-sIgG levels showed a significant correlation with "ear/facial" symptom scores in the T2 group (P < .001). CONCLUSIONS: Serum Af-sIgG levels may serve as a supplementary objective biomarker that correlates with identification and subjective measurements of T2 CRS, and may be associated with symptoms arising from Eustachian tube dysfunction.

A modified drag coefficient model for calculating the terminal settling velocity and horizontal diffusion distance of irregular plume particles in deep-sea mining.

Deep-sea mining inevitably produces plumes, which will pose a serious threat to the marine environment with the continuous movement and diffusion of plumes along with ocean currents. The terminal settling velocity (wt) of irregular particles is one of the crucial factors for determining the plumes' diffusion range. It is generally calculated by drag coefficient (CD), while most existing CD models only consider single shape characteristic parameter or have a smaller range of Reynolds number (Re). In this study, a new shape factor (γ) of irregular particles is proposed by considering the thickness (one-dimension), the projected area (two-dimension), and the surface area (three-dimension) of irregular particles as well as their coupling effect to establish a modified CD model for calculating the wt. A modified Gaussian plume model is proposed to predict the horizontal diffusion distance of the plume particles by considering the settling velocity and diffusion effect of irregular particles. Research results show that the wt increases nearly linearly, with a gradually decreased slope and slightly then greatly with the increasing of γ, dp (diameter) and ρp (density), respectively. The modified CD model is verified to be more valid with a wider application range (Re < 3×105) than five existing CD models by the test results. The larger the ρp or dp, the larger the wt and thus the smaller the Sh. This study could provide a theoretical basis for calculating the plume diffusion range to further study the impact of deep-sea mining on the ocean environment.

Centromeric chromatin clearings demarcate the site of kinetochore formation.

The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. The kinetochore has been interrogated by electron microscopy since the middle of the last century, but with methodologies that compromised fine structure. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20-25 nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing. We further visualize the scaffold of the fibrous corona, a structure amplified at unattached kinetochores, revealing crescent-shaped parallel arrays of fibrils that extend >1 µm. Thus, we reveal how the organization of centromeric chromatin creates a clearing at the site of kinetochore formation as well as the nature of kinetochore amplification mediated by corona fibrils.

Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

Snuffbox distal transradial access (dTRA) for arteriovenous fistuloplasty in Singapore: Going distal is safe.

AIM: Arteriovenous fistula (AVF) dysfunction resulting from stenosis or occlusion, is a prevalent issue in end-stage renal failure patients reliant on autogenous AVFs for dialysis. Recently, a distal transradial approach (dTRA) has emerged, offering advantages such as diminished access site complications, better patient comfort and reduced risk of radial artery occlusion. Our study seeks to assess the effectiveness, outcomes and complication rates of employing dTRA for arteriovenous fistuloplasty in Singaporean patients. METHODS: A retrospective review of all dTRA fistuloplasties performed on dysfunctional or slow to mature AVFs from 2017 to 2023 in our institution was performed. Patients with a distal radial artery measuring 2 mm or more with no evidence of occlusion or thrombosis were included. Patients who required central venoplasty or cutting balloon angioplasty were excluded. Outcome measures included technical success, mean procedure duration, complications and post-intervention primary patency at 1, 3 and 6 months. Patients were followed up for 12 months post-intervention. RESULTS: A total of 37 patients were included. 97.3% of patients undergoing dTRA fistuloplasty had radiocephalic fistulas while 2.7% had brachiobasilic fistulas. There was 100% technical success (defined as success in radial artery cannulation, sheath insertion and crossing of stenotic lesions) in our study as all patients successfully underwent fistuloplasty via dTRA approach. One-month patency rate was 97.4%, 3-month patency rate was 92.1% and 6-month patency rate was 86.8%. There were no immediate complications (haematoma, infection, bleeding, pseudoaneurysm, occlusion) of the radial artery post-intervention. CONCLUSION: Our paper illustrates the safety and efficacy of utilising dTRA for arteriovenous fistuloplasty. This approach offers distinct benefits in addressing non-mature or dysfunctional distal forearm arteriovenous fistulas and should be taken into account in anatomically suitable cases.

Factors Impacting Fall Severity in Hospitalized Patients: A Retrospective Cohort Study.

Objectives: This retrospective case-controlled study aimed to evaluate the association between the severity of fall-related injuries and fall-risk-increasing drugs (FRIDs) in hospitalized patients. Methods: Data were collected from Changhua Christian Hospital, Taiwan, of all adult inpatients who experienced falls between January 2017 and December 2021, and were divided into two groups based on whether they sustained severe fall-related injuries. Retrospective data that may affect the severity of fall-related injuries and the use of FRIDs were investigated. Results: Among 1231 documented cases of falls, 26 patients sustained severe fall-related injuries. Older patients and those with osteoporosis were more susceptible to more severe injuries from a fall. The use of mobility aids and osteoporosis medications showed protective effects against fall injuries. No significant association was observed between fall-related injuries and comorbidities or FRIDs. Multivariate analysis confirmed the inverse correlation between the use of mobility aids, osteoporosis medications, and fall severity. Patients with osteoporosis exhibited significantly higher odds of sustaining more severe injuries with a fall (odds ratio = 3.02, 95% confidence interval: 1.21-7.53). Conclusions: This study highlights the importance of addressing risk factors associated with fall severity among hospitalized patients. Providing mobility aids to persons at greater risk.

Pumilio RNA binding family member 1 deficiency activates anti-tumor immunity in hepatocellular carcinoma via restraining M2 macrophage polarization.

Pumilio RNA-binding family member 1 (PUM1) has been implicated in both the progression of colorectal cancer and the regulation of inflammation. The role of PUM1 in the polarization of tumor-associated macrophages (TAMs) into the M2 phenotype has not yet been reported in hepatocellular carcinoma. Using the PUM1-knockout mice model, flow cytometry, and IHC, we validated the role of PUM1 in hepatocellular carcinoma (HCC) TAMs. One-way analysis of variance (ANOVA) or student's t-tests was used to compare the experimental groups. We found that PUM1 inhibited anti-tumor immunity in HCC through TAM-mediated inhibition of CD8+ T cells. We also showed that PUM1 promotes the transformation of TAMs into pro-tumorigenic M2-like phenotypes by activating cAMP signaling pathway. This study emphasized the potential of PUM1 as a target for immunotherapy in HCC through TAMs. The present study revealed the molecular mechanism underlying the pro-tumor role of PUM1 in HCC.

Self acceleration from spectral geometry in dissipative quantum-walk dynamics.

The dynamic behavior of a physical system often originates from its spectral properties. In open systems, where the effective non-Hermitian description enables a wealth of spectral structures in the complex plane, the concomitant dynamics are significantly enriched, whereas the identification and comprehension of the underlying connections are challenging. Here we experimentally demonstrate the correspondence between the transient self-acceleration of local excitations and the non-Hermitian spectral topology using lossy photonic quantum walks. Focusing first on one-dimensional quantum walks, we show that the measured short-time acceleration of the wave function is proportional to the area enclosed by the eigenspectrum. We then reveal a similar correspondence in two-dimension quantum walks, where the self-acceleration is proportional to the volume enclosed by the eigenspectrum in the complex parameter space. In both dimensions, the transient self-acceleration crosses over to a long-time behavior dominated by a constant flow at the drift velocity. Our results unveil the universal correspondence between spectral topology and transient dynamics, and offer a sensitive probe for phenomena in non-Hermitian systems that originate from spectral geometry.

TransEBUS: The interpretation of endobronchial ultrasound image using hybrid transformer for differentiating malignant and benign mediastinal lesions.

The purpose of this study is to establish a deep learning automatic assistance diagnosis system for benign and malignant classification of mediastinal lesions in endobronchial ultrasound (EBUS) images. EBUS images are in the form of video and contain multiple imaging modes. Different imaging modes and different frames can reflect the different characteristics of lesions. Compared with previous studies, the proposed model can efficiently extract and integrate the spatiotemporal relationships between different modes and does not require manual selection of representative frames. In recent years, Vision Transformer has received much attention in the field of computer vision. Combined with convolutional neural networks, hybrid transformers can also perform well on small datasets. This study designed a novel deep learning architecture based on hybrid transformer called TransEBUS. By adding learnable parameters in the temporal dimension, TransEBUS was able to extract spatiotemporal features from insufficient data. In addition, we designed a two-stream module to integrate information from three different imaging modes of EBUS. Furthermore, we applied contrastive learning when training TransEBUS, enabling it to learn discriminative representation of benign and malignant mediastinal lesions. The results show that TransEBUS achieved a diagnostic accuracy of 82% and an area under the curve of 0.8812 in the test dataset, outperforming other methods. It also shows that several models can improve performance by incorporating two-stream module. Our proposed system has shown its potential to help physicians distinguishing benign and malignant mediastinal lesions, thereby ensuring the accuracy of EBUS examination.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis.

OBJECTIVE: To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. METHODS: 122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. RESULTS: The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. CONCLUSION: Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

Cost-effectiveness of diabetic retinopathy screening for newly diagnosed type 2 diabetic patients: A nationwide population-based propensity score-matched cohort study.

AIMS: This study investigated the association between the frequency of screening for diabetic retinopathy (DR) versus the development of DR and corresponding medical expenses among patients newly diagnosed with type 2 diabetes mellitus (T2DM). METHODS: This longitudinal, population-based study used the Taiwan National Health Insurance Research Database (2004 to 2020) as a data source. Propensity score matching (PSM) (sex, age, comorbidities and concurrent medication use) was employed in the grouping of T2DM patients according to different frequency of DR screening. Outcome measures included the proportion of patients who developed DR, who received DR treatment, and the associated medical expenses and hospitalizations. RESULTS: The 17-year cohort included 337,046 patients. After PSM, three groups each containing 35,739 patients were assembled and analyzed. Compared to low-frequency screening, high-frequency screening was more effective in detecting patients requiring treatment; however, the net cost for treatment was significantly lower. Standard-frequency screening appears to provide the best balance in terms of DR detection, diagnosis interval, the risk of DR-related hospitalization, and DR treatment costs. CONCLUSIONS: In this real-world cohort study covering all levels of the healthcare system, infrequent screening was associated with delayed diagnosis and elevated treatment costs, while a fundus screening interval of 1-2 years proved optimal in terms of detection and medical expenditures.

The clinical practice and dosimetric outcome of the manual adaptive planning during definitive radiotherapy for cervical cancer.

PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.

Itaconate as a key player in cardiovascular immunometabolism.

Cardiovascular diseases (CVDs) are the leading cause of death globally, resulting in a major health burden. Thus, an urgent need exists for exploring effective therapeutic targets to block progression of CVDs and improve patient prognoses. Immune and inflammatory responses are involved in the development of atherosclerosis, ischemic myocardial damage responses and repair, calcification, and stenosis of the aortic valve. These responses can involve both large and small blood vessels throughout the body, leading to increased blood pressure and end-organ damage. While exploring potential avenues for therapeutic intervention in CVDs, researchers have begun to focus on immune metabolism, where metabolic changes that occur in immune cells in response to exogenous or endogenous stimuli can influence immune cell effector responses and local immune signaling. Itaconate, an intermediate metabolite of the tricarboxylic acid (TCA) cycle, is related to pathophysiological processes, including cellular metabolism, oxidative stress, and inflammatory immune responses. The expression of immune response gene 1 (IRG1) is upregulated in activated macrophages, and this gene encodes an enzyme that catalyzes the production of itaconate from the TCA cycle intermediate, cis-aconitate. Itaconate and its derivatives have exerted cardioprotective effects through immune modulation in various disease models, such as ischemic heart disease, valvular heart disease, vascular disease, heart transplantation, and chemotherapy drug-induced cardiotoxicity, implying their therapeutic potential in CVDs. In this review, we delve into the associated signaling pathways through which itaconate exerts immunomodulatory effects, summarize its specific roles in CVDs, and explore emerging immunological therapeutic strategies for managing CVDs.

Systemic Immune-Inflammation Index and Systemic Inflammation Response Index are Associated With Periodontitis: Evidence From NHANES 2009 to 2014.

INTRODUCTION AND AIMS: Periodontitis, a chronic inflammatory condition affecting the supporting structures of the teeth, is a substantial public health burrden whilst impacting the life quality of those affected. Elevated levels of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have been implicated in various inflammatory conditions. This study aimed to investigate the relationship between SII and SIRI with periodontitis. METHODS: The study examined a total of 8666 participants in the 2009 to 2014 National Health and Nutrition Examination Survey (NHANES). The study compared the weighted prevalence of periodontitis among various groups. The association between SII, SIRI levels, and periodontitis was analyzed using binary logistic regression. Additionally, we explored nonlinear relationships between SII, SIRI, and the prevalence of periodontitis using restricted cubic spline (RCS) plots. RESULTS: Among participants in the fourth quartile (Q4) of SII and SIRI, the highest prevalence of periodontitis was observed, with rates of 44.87% and 48.41%, respectively. After adjusting for all covariates, the odds ratio (OR) for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.18 (95% CI 1.01, 1.39, P = .04). In addition, the results of sensitivity analysis revealed consistent findings, indicating that after adjusting for all covariates, the OR for periodontitis associated with SII Q4 and SIRI Q4 remained statistically significant. Specifically, the OR for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.19 (95% CI 1.01, 1.40, P = .04). CONCLUSIONS: These results indicate that elevated SII and SIRI levels are associated with an increased prevalence of periodontitis. CLINICAL RELEVANCE: These findings suggest a potential connection between systemic inflammation and periodontitis, highlighting the importance of periodontitis patients being aware of their systemic diseases that are inflammatory in nature such as chronic cardiovascular afflictions.