Background: Patients with systemic autoimmune diseases (sAIDs) are susceptible to active tuberculosis (ATB), especially in high-burden countries and regions. However, a comprehensive overview of the ATB burden across the full spectrum of sAIDs remains lacking. Methods: In this nationwide retrospective cohort study, we linked individual-level data from the Chinese Rheumatism Data Center (CRDC), the Infectious Disease Reporting System (IDRS), and the Tuberculosis Information Management System (TBIMS). Patients of all ages registered in CRDC between 2016 and 2023, with a confirmed diagnosis of 1 of 10 sAIDs, including rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, primary Sjögren's disease, idiopathic inflammatory myopathies, undifferentiated connective tissue disease, systemic sclerosis, Behçet's disease (BD), Takayasu arteritis (TAK), and ANCA-associated vasculitis (AAV), were included. We estimated incidence rates, point prevalence, cumulative incidence, and age- and gender-adjusted standardized incidence ratios (SIRs) for ATB, and examined associations between SIRs and region-level socioeconomic indicators using Cox proportional hazards models. Findings: Among 255,103 eligible patients, 2,775 incident ATB cases were confirmed across all 10 sAIDs. The overall ATB incidence rate in 2023 was 157.79 per 100,000 person-years. Point prevalence of ATB among patients with sAIDs rose from 393.83 per 100,000 people in 2016 to 904.65 per 100,000 people in 2023. Cumulative incidence exceeded 1% within 10 years of sAID diagnosis. Patients with TAK (7.60, 95% CI 4.92-11.22), AAV (6.96, 4.90-9.59), BD (6.30, 4.25-9.00) carried the highest relative risks of ATB, and male and female patients exhibited comparable ATB susceptibility compared with general population. At the area level, higher urbanization was associated with increased ATB risk in patients with sAIDs, whereas higher educational attainment was protective. Interpretations: Patients with sAIDs constitute a distinctly high-risk population for ATB, with a burden substantially exceeding that of the general population and marked heterogeneity across diseases and socioeconomic context. These findings support the systematic integration of targeted TB screening and preventive strategies into routine rheumatology care, particularly in TB-endemic settings.

Aerosol therapy is frequently used in adults with acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, yet its clinical effects remain difficult to interpret because prescribed dose is not equivalent to lung exposure. This Mini Review examines aerosol therapy as a drug-device-circuit-patient intervention by integrating ARDS guideline context, delivery evidence, drug-class literature, and implementation data. Exposure is shaped by generator and formulation, fill and residual volume, position, humidification, ventilator flow, artificial airway, filters, inline components, and interruptions. Most technical evidence is bench-derived and does not establish ARDS-specific clinical benefit. We retain gaseous inhaled nitric oxide only as a non-aerosol physiological comparator. Nebulized prostacyclins may improve oxygenation, but patient-centered benefit remains uncertain; aerosolized antibiotics should be interpreted within infection-defined ventilator-associated pneumonia; and bronchodilators or mucoactive therapies should not be used routinely on the basis of the ARDS label alone. Optimization should seek reproducible, target-appropriate exposure while preserving lung-protective ventilation, circuit integrity, treatment continuity, filtration surveillance, and staff and environmental safety. We propose a candidate minimum delivery-reporting dataset, while emphasizing that it is not a validated exposure surrogate or clinical score. Future studies should align mechanism, delivery, phenotype, response window, safety, and patient-centered endpoints to distinguish biological failure from inadequate or interrupted exposure.

Abstract Whether low peripheral oxygen saturation (SpO2) directed oxygen therapy is associated with lower mortality in critically ill patients needs further exploration. Adult critically ill patients from 11 intensive care units in China were screened. Participants were randomly assigned to the low SpO2 (90%–95%) group or the high SpO2 (≥96%) ‐group. The primary outcome was 28‐day all‐cause mortality. The secondary outcomes were hours free from ventilators and from renal replacement therapy (RRT) within 14 days. Note that 857 patients in the low SpO2 group and 849 in the high SpO2 group were included. In the low SpO2 group versus the high SpO2 group, the time‐weighted average of the fraction of inspired oxygen (FiO2) was significantly lower (33.5 ± 9.7% vs. 39.6 ± 9.3%, p < 0.001), and so was the time‐weighted average of SpO2 (95.9 ± 1.8% vs. 98.0 ± 1.9%, p < 0.001). Within 28 days after randomization, 172 (20.1%) in the low SpO2 group and 193 (22.7%) in the high SpO2 group died (p = 0.180). Ventilator‐free time and RRT‐free time were not significantly different within 14 days. In critically ill patients, low SpO2directed oxygen therapy did not decrease 28‐day mortality, 14‐day ventilator‐free time, or 14‐day RRT‐free time.

BACKGROUND:The effect of immunosuppression on clinical manifestations and outcomes was unclear in elderly patients with CAP. METHODS:Elderly hospitalised patients with CAP were consecutively enrolled and were divided into immunocompromised hosts (ICHs) or non-ICHs groups. Clinical manifestations, severity, and outcomes were compared. The logistic regression model was used to determine the association between immunosuppression and outcomes. The primary outcome was 30-day mortality. RESULTS:A total of 822 patients were enrolled, of whom 133 (16.2%) were immunocompromised. There were no differences between the two groups in vital signs, oxygenation, admission laboratory tests, need for mechanical ventilation and intensive care unit admission, except for a lower lymphocyte count in the ICH group (0.9*10^9/L, IQR 0.6-1.3*10^9/L [ICH group] vs. 1.2*10^9/L, IQR 0.8-1.7*10^9/L [non-ICH group]; p < 0.001). The 30-day mortality in ICHs was 15.8%, significantly higher than the 5.1% in non-ICHs (p < 0.001). The risk distribution of severity was similar between the two groups when assessed by CURB-65 on admission; however, the significant difference was found when assessed by PSI. Notably, in the CURB-65 low-risk group, the 30-day mortality was significantly higher in ICHs than in non-ICHs (9.7% vs. 1.1%, p < 0.001); but there was no difference between ICHs and non-ICHs in PSI low-risk group (3.7% vs. 0.6%; p > 0.05). After adjusting for age, sex, and comorbidities, immunosuppression was significantly associated with a higher risk of 30-day mortality (odds ratio 5.004, 95% CI [2.618-9.530]). CONCLUSIONS:Immunosuppression was independently associated with an increased risk of 30-day mortality. CURB-65 may underestimate the mortality risk of ICHs.

ObjectiveThe prognostic value of the systemic immune-inflammation index (SII) for prostate cancer (PCa) patients receiving different treatments remains unclear. This research examined the relevance of SII in individuals undergoing radical prostatectomy (RP).MethodsPubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI) dat3 abases were used to search literature up to May 2024. The quality was evaluated with Newcastle-Ottawa Scale. Outcomes examined were associations between SII and overall survival (OS), biochemical recurrence-free survival (BFS), and cancer-specific survival (CSS). Pooled analysis, Egger’s test, and sensitivity analysis were conducted using Review Manager 5.4.1 and Stata 15.1. The GRADE system was employed to evaluate and grade the evidence for each outcome. Subgroup analyses were performed for outcomes with significant heterogeneity to evaluate the possible confounders, if data were sufficient.ResultsOut of 101 identified studies, eight studies involving 8,267 individuals were included. Patients with higher SII had shorter overall survival (HR: 1.89; 95% CI: 1.31-2.71; P = 0.0006), biochemical recurrence-free survival (HR: 1.55; 95% CI: 1.08-2.22; P = 0.02), and cancer-specific survival (HR: 3.63; 95% CI: 1.66-7.94; P = 0.001). The evidence for OS and CSS was rated very low-quality due to serious heterogeneity and/or imprecision. The prognostic value of SII for BFS was rated as low-quality evidence, given no serious risk observed. Subgroup analysis showed that, except for the subgroup aged >65 years (HR: 3.70; 95%CI: 0.91, 15.06, P=0.07), the prognostic value of SII for OS was not significant, but the prognostic value of SII for OS in other subgroups was still significant.ConclusionsHigh SII was linked to shorter OS, BFS, and CSS in patients undergoing RP. However, the quality of the evidence provided by this study was low.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024558431.

Medical professionals in thoracic medicine routinely analyze chest X-ray images, often comparing pairs of images taken at different times to detect lesions or anomalies in patients. This research aims to design a computer-aided diagnosis system that enhances the efficiency of thoracic physicians in comparing and diagnosing X-ray images, ultimately reducing misjudgments. The proposed system encompasses four key components: segmentation, alignment, comparison, and classification of lung X-ray images. Utilizing a public NIH Chest X-ray14 dataset and a local dataset gathered by the Chiayi Christian Hospital in Taiwan, the efficacy of both the traditional methods and deep-learning methods were compared. Experimental results indicate that, in both the segmentation and alignment stages, the deep-learning method outperforms the traditional method, achieving higher average IoU, detection rates, and significantly reduced processing time. In the comparison stage, we designed nonlinear transfer functions to highlight the differences between pre- and post-images through heat maps. In the classification stage, single-input and dual-input network architectures were proposed. The inclusion of difference information in single-input networks enhances AUC by approximately 1%, and dual-input networks achieve a 1.2–1.4% AUC increase, underscoring the importance of difference images in lung disease identification and classification based on chest X-ray images. While the proposed system is still in its early stages and far from clinical application, the results demonstrate potential steps forward in the development of a comprehensive computer-aided diagnostic system for comparative analysis of chest X-ray images.

Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF’s protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF’s mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF’s ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis.

Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields. This article summarizes key insights from IRM2024, held in Shanghai, where a wide range of topics were discussed, including lung tissue development, disease mechanisms, and innovative therapeutic strategies. By integrating perspectives from basic, translational, and clinical research, IRM2024 highlighted recent advancements, addressed persistent challenges, and explored future directions in respiratory science and clinical practice. The insights gained from IRM2024 are poised to be pivotal in shaping future research and therapeutic approaches, further reinforcing the global commitment to enhancing respiratory health and improving patient outcomes.

A novel kefir exopolysaccharides (KEPS) derived from kefir grain fermentation were found to have a small molecular weight (12 kDa) compared to the traditionally high molecular weight (12,000 kDa) of kefiran (KE). KE has been shown to possess antioxidant, blood pressure-lowering, and immune-modulating effects. In this study, we characterized KEPS and KE and evaluated their anti-inflammatory properties in vitro using RAW264.7 macrophages. The main monosaccharide components were identified as glucose (98.1 ± 0.06%) in KEPS and galactose (45.36 ± 0.16%) and glucose (47.13 ± 0.06%) in KE, respectively. Both KEPS and KE significantly reduced IL-6 secretion in lipopolysaccharide (LPS)-stimulated macrophages. We further investigated their effects in LPS-induced systemic injury in male and female NF-κB-luciferase+/+ transgenic mice. Mice received oral KEPS (100 mg/kg) or KE (100 mg/kg) for seven days, followed by LPS or saline injection. KEPS and KE inhibited NF-κB signaling, as indicated by reduced luciferase expression and phosphorylated NF-κB levels. LPS-induced systemic injury increased luciferase signals, especially in the kidney, spleen, pancreas, lung, and gut tissues of female mice compared to male mice. Additionally, it upregulated inflammatory mediators in these organs. However, KEPS and KE effectively suppressed the expression of inflammatory mediators, including p-MAPK and IL-6. These findings demonstrate that KEPS can alleviate LPS-induced systemic damage by inhibiting NF-κB/MAPK signaling, suggesting their potential as a treatment for inflammatory disorders.

Aims: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model.Main methods: After the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro, IL-1 beta-treated human synovial cells (SW982) were subjected to anti -arthritis mechanism study in the presence of KPs.Key findings: The results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-Kappa B and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1 beta-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1 beta-related inflammation and MMPs production.Significance: We concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage -related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis.

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D-glucuronate to L-gulonate in the synthesis of L-ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice (AKR1A1eGFP/eGFP) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1eGFP/eGFP mice were used in this study, in which the AKR1A1eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1β, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). μ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, β-catenin, BMP-2, NFATc1). Conversely, KPs inhibited bone marrow macrophages (BMMs)-derived osteoclast differentiation and bone resorption, which was demonstrated by the facts that KPs suppressed RANKL-induced p38, NF-κB, Akt, PLCγ2 and CREB-1 phosphorylation, decreased the nuclear translocation of NFATc1 and c-Fos. Our findings demonstrate the efficacy of KPs in the prevention of osteoporosis in AKR1A1eGFP/eGFP mice and also unveil the dual effects of KPs in osteogenic promotion and osteoclastic inhibition. This study supports the use of KPs as nutritional supplements for the prevention of osteoporosis.

Acute respiratory distress syndrome (ARDS) is a common destructive syndrome with high morbidity and mortality rates. Currently, few effective therapeutic interventions for ARDS are available. Clinical trials have shown that the effectiveness of aspirin is inconsistent. The contribution of platelets to the inflammatory response leading to the development of ARDS is increasingly recognized. The antiplatelet agent aspirin reportedly exerts a protective effect on acid- and hyperoxia-induced lung injury in murine models. Our previous study showed that pretreatment with aspirin exerts protective effects on hyperoxia-induced lung injury in mice. However, the mechanisms and therapeutic efficacy of aspirin in the posttreatment of hyperoxia-induced acute lung injury (ALI) remain unclear. In this study, we used a homozygous NF-κB-luciferase+/+ transgenic mouse model and treated mice with low-dose (25 μg/g) or high-dose (50 μg/g) aspirin at 0, 24, and 48 h after exposure to hyperoxia (inspired oxygen fraction (FiO2) > 95%). Hyperoxia-induced lung injury significantly increased the activation of NF-κB in the lung and increased the levels of macrophages infiltrating the lung and reactive oxygen species (ROS), increased the HO-1, NF-κB, TNF-α, IL-1β, and IL-4 protein levels, and reduced the CC10, SPC, eNOS, Nrp-1, and IκBα protein levels in the lung tissue. Pulmonary edema and alveolar infiltration of neutrophils were also observed in the lung tissue of mice exposed to hyperoxia. However, in vivo imaging revealed that posttreatment with aspirin reduced luciferase expression, suggesting that aspirin might reduce NF-κB activation. Posttreatment with aspirin also reduced hyperoxia-induced increases in the numbers of lung macrophages, intracellular ROS levels, and the expression of TNF-α, IL-1β, and IL-4; it also increased CC10, SPC and Nrp-1 levels compared with hyperoxia exposure alone. Lung histopathology also indicated that the aspirin posttreatment significantly reduced neutrophil infiltration and lung edema compared with hyperoxia exposure alone. Aspirin effectively induces an anti-inflammatory response in a model of hyperoxia-induced lung injury. Thus, aspirin may have potential as a novel treatment for hyperoxia-induced ALI.

Inverted repeat (IR) DNA sequences compose cruciform structures. Some genetic disorders are the result of genome inversion or translocation by cruciform DNA structures. The present study examined whether exogenous DNA integration into the chromosomes of transgenic animals was related to cruciform DNA structures. Large imperfect cruciform structures were frequently predicted around predestinated transgene integration sites in host genomes of microinjection-based transgenic (Tg) animals (αLA-LPH Tg goat, Akr1A1eGFP/eGFP Tg mouse, and NFκB-Luc Tg mouse) or CRISPR/Cas9 gene-editing (GE) animals (αLA-AP1 GE mouse). Transgene cassettes were imperfectly matched with their predestinated sequences. According to the analyzed data, we proposed a putative model in which the flexible cruciform DNA structures acted as a legible template for DNA integration into linear DNAs or double-strand break (DSB) alleles. To demonstrate this model, artificial inverted repeat knock-in (KI) reporter plasmids were created to analyze the KI rate using the CRISPR/Cas9 system in NIH3T3 cells. Notably, the KI rate of the 5′ homologous arm inverted repeat donor plasmid (5′IR) with the ROSA gRNA group (31.5%) was significantly higher than the knock-in reporter donor plasmid (KIR) with the ROSA gRNA group (21.3%, p < 0.05). However, the KI rate of the 3′ inverted terminal repeat/inverted repeat donor plasmid (3′ITRIR) group was not different from the KIR group (23.0% vs. 22.0%). These results demonstrated that the legibility of the sequence with the cruciform DNA existing in the transgene promoted homologous recombination (HR) with a higher KI rate. Our findings suggest that flexible cruciform DNAs folded by IR sequences improve the legibility and accelerate DNA 3′-overhang integration into the host genome via homologous recombination machinery.

Taiwan is predicted to become a super-aged society by 2025, and primary health centers (PHCs) are set to play a crucial role in the care of older adults. The Taiwanese government has developed an age-friendly verification framework for PHC. The aims of this study were to explore the difficulties faced by PHC staff in the implementation of age-friendly policies and their solution strategies. This study adopted a qualitative research method. The first stage involved conducting five focus groups with the responsible staff of PHCs (n = 41) that have been certified “age-friendly.” The focus groups covered the effectiveness, difficulties, and resources of PHCs in regards to the introduction of age-friendly policies. In the second stage, in-depth interviews were conducted with executives of PHCs (n = 5), both certified and not certified as age-friendly, to further compare the difficulties faced by these two types of PHCs, thereby gaining perspectives for solution strategies. The principles of grounded theory were used for data analysis. Four major PHC strategies are employed in the promotion of age-friendliness. First, organizational management, through which managers apply management methods and analyze the present PHC-related health concerns; second, resource utilization, which refers to the tallying, linking, and integrating of resources; third, business operation process, in which work efficiency is improved through the combination of business operations and staff training; finally, hardware improvement, which is achieved through comprehensive cataloging of facility environments. The implementation of age-friendliness in PHCs requires the efforts of both the service units and government. With resources provided by the government, PHCs can integrate management methods, businesses operations, and essential resources. Moreover, PHC executives can lead their teams in promoting age-friendly policies, and closely monitor their effectiveness.

Osteoporosis is a clinically prevalent comorbidity in patients with hemophilia. A preventive effect of kefir peptides (KPs) on postmenopausal osteoporosis has been proved. The aim of this study was to evaluate the therapeutic effect of KPs for the treatment of osteoporosis in coagulation factor VIII (FVIII) gene knockout mice (F8KO), a model of hemophilia A. In this study, male F8KO mice at 20 weeks of age were orally administered different doses of KPs for 8 weeks. The therapeutic effects of KPs were shown in the femoral trabeculae and the 4th lumbar vertebrae, which increased the trabecular bone mineral density (BMD), bone volume (Tb.BV/TV), and trabecular number (Tb.N) and decreased the trabecular separation (Tb.Sp), and they were also observed in the femoral cortical bones, in which the mechanical properties were enhanced in a dose-dependent manner. Characterization of receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and interleukin 6 (IL-6) demonstrated that the serum RANKL/OPG ratio and IL-6 levels were significantly decreased in the F8KO mice after the KP treatment. Tartrate-resistant acid phosphatase (TRAP) staining of mature osteoclasts indicated that the therapeutic effect of KPs in F8KO mice was associated with the functions of KPs to inhibit RANKL-induced osteoclastogenesis by reducing serum RANKL/OPG ratio and IL-6 secretion. The present study is the first to address the potentials of KPs for the treatment of hemophilia-induced osteoporosis in mice and it also provides useful information for the application of KPs as a complementary therapy for the treatment of osteoporosis in hemophilic patients.

Clinical Nephrology is a specialty of medicine that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy including dialysis and kidney transplantation. The Journal of Clinical Nephrology is an initiative of Heighten Science Publication to publish distinctive and scholarly manuscripts that can play astounding role in enhancing the excellence and confidence of the doctors, scientists and researchers associated in the studies related to renal medicine, hypertension and other related fields of Clinical Nephrology.

Background Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. Methods To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. Results An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. Conclusions Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.

End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients.

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.

Purpose This systematic review and meta-analysis aimed to synthesize the evidence on the effect of couple-based interventions on quality of life (QOL) among prostate cancer patients and their spouses. Method Six English databases and two Chinese databases were systematically searched to identify relevant RCTs that examined the effect of couple-based interventions on QOL. The data from the included studies were extracted by two independent reviewers using a standardized data extraction form. Methodological quality was assessed by using the Cochrane Risk of Bias Tool. Meta-analysis was conducted among the suitable studies that the available data were sufficient. Results One thousand ninety-five studies were identified, and 11 studies met the inclusion criteria for qualitative synthesis and 7 studied for meta-analysis. Couple-based interventions involve different formats of physical and psychosocial interventions. Physical exercise-based interventions were popular among couples, and these interventions had the highest level of adherence among all interventions examined herein. However, the meta-analysis of total QOL and physical and mental health revealed a non-significant effect on both prostate cancer patients and their spouses. More RCTs examining couple-based interventions may be needed in developing countries, especially in Asian countries. Conclusion Couple-based interventions had non-significant effect on improving the total QOL and physical and mental health of prostate cancer patients and their spouses. However, the current evidence is limited because the sample size of the studies is small. Thus, more studies with large sample sizes need to be included to detect the efficacy of couple-based interventions on prostate cancer patients and their spouses.