Search

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Abstract Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient‐derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF‐κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

Background/Purpose: Thirty-day hospital readmission rate significantly raised with advanced age. The performance of existing predictive models for readmission risk remained uncertain in the oldest population. We aimed to examine the effect of geriatric conditions and multimorbidity on readmission risk among older adults aged 80 and over. Methods: This prospective cohort study enrolled patients aged 80 and older discharged from a geriatric ward at a tertiary hospital, with phone follow-up for 12 months. Demographics, multimorbidity, and geriatric conditions were assessed before hospital discharge. Logistic regression models were conducted to analyse risk factors for 30-day readmission. Results: Patients readmitted had higher Charlson comorbidity index scores, and were more likely to have falls, frailty, and longer hospital stay, compared to those without 30-day readmission. Multivariate analysis revealed that higher Charlson comorbidity index score was associated with readmission risk. Older patients with a fall history within 12 months had a near 4-fold increase in readmission risk. Severe frailty status before index admission was associated with a higher 30-day readmission risk. Functional status at discharge was not associated with readmission risk. Conclusion: In addition to multimorbidity, history of falls and frailty were associated with higher hospital readmission risk in the oldest.

ObjectiveThe aim of this study was to evaluate the dietary exposure level of chromium （Cr） and its potential health risks among residents of Chongqing.MethodsCr concentration data were obtained from the Food Safety Risk Monitoring System， which included 2 780 Cr-containing food samples from nine categories in Chongqing from 2018 to 2021. Food consumption data were derived from the Chongqing Diet Survey Data of the China Health and Nutrition Survey Project 2018 （3 d 24 h dietary recall surveys）. A Monte Carlo simulation was used to estimate the dietary Cr intake levels and the associated health risks.ResultsThe average concentration of Cr in all foods in Chongqing ranged from 0.013 9 to 0.126 3 mg/kg， with a total detection rate of 40.6%. The average Cr concentration was highest in aquatic products， followed by foods for special dietary use， leafy vegetables， and rice. The average daily dietary Cr exposure range of Chongqing residents was 0.683-2.117 μg/kg body weight （BW）， and the dietary Cr exposure level （P95） of the high-food-consumption population was 1.165-3.597 μg/kg BW. The average daily level of Cr exposure decreased with increasing age. The average daily exposure to Cr was highest for people aged 1-6 years and lowest for people aged >60 years. The average exposure to Cr was higher in urban areas than in rural areas， and females had higher exposure levels than males. Cereals and their products had the highest contribution to the total dietary Cr exposure of Chongqing residents， reaching 39.31%-49.13%. The mean and maximum levels of exposure （P95） to chromium were less than one of the tolerable daily intake in all age， sex， and regional groups.ConclusionThe health risk of dietary Cr exposure among Chongqing residents was low. The three main sources of dietary Cr were cereals and their products， vegetables， and meat.

Abstract Introduction As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. Case presentation We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. Conclusion The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

Abstract Background Diabetic cardiomyopathy (DCM) represents a major cause of heart failure and a large medical burden worldwide. This study screened the potentially regulatory targets of DCM and analyzed their roles in high glucose (HG)‐induced cardiomyocyte injury. Methods Through GEO database, we obtained rat DCM expression chips and screened differentially expressed genes. Rat cardiomyocytes (H9C2) were induced with HG. 3‐hydroxy‐3‐methylglutarylcoenzyme A synthase 2 (Hmgcs2) and microRNA (miR)‐363‐5p expression patterns in cells were measured by real‐time quantitative polymerase chain reaction or Western blot assay, with the dual‐luciferase assay to analyze their binding relationship. Then, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay, lactate dehydrogenase assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme‐linked immunosorbent assay, and various assay kits were applied to evaluate cell viability, cytotoxicity, apoptosis, inflammation responses, and oxidative burden. Results Hmgcs2 was the vital hub gene in DCM. Hmgcs2 was upregulated in HG‐induced cardiomyocytes. Hmgcs2 downregulation increased cell viability, decreased TUNEL‐positive cell number, reduced HG‐induced inflammation and oxidative stress. miR‐363‐5p is the upstream miRNA of Hmgcs2. miR‐363‐5p overexpression attenuated HG‐induced cell injury. Conclusions Hmgcs2 had the most critical regulatory role in DCM. We for the first time reported that miR‐363‐5p inhibited Hmgcs2 expression, thereby alleviating HG‐induced cardiomyocyte injury.

Maintaining open flowers is critical for successful pollination and depends on long-term water and carbon balance. Yet the relationship between how flower hydraulic traits are coordinated in different habitats is poorly understood. Here, we hypothesize that the coordination and trade-offs between floral hydraulics and economics traits are independent of environmental conditions. To test this hypothesis, we investigated a total of 27 flower economics and hydraulic traits in six aquatic and six terrestrial herbaceous species grown in a tropical botanical garden. We found that although there were a few significant differences, most flower hydraulics and economics traits did not differ significantly between aquatic and terrestrial herbaceous plants. Both flower mass per area and floral longevity were significantly positively correlated with the time required for drying full-hydrated flowers to 70% relative water content. Flower dry matter content was strongly and positively related to drought tolerance of the flowers as indicated by flower water potential at the turgor loss point. In addition, there was a trade-off between hydraulic efficiency and the construction cost of a flower across species. Our results show that flowers of aquatic and terrestrial plants follow the same economics spectrum pattern. These results suggest a convergent flower economics design across terrestrial and aquatic plants, providing new insights into the mechanisms by which floral organs adapt to aquatic and terrestrial habitats.

Background and purpose: Bone metastatic tumor is a common disease of tumor bone metastasis, and the prognosis of patients is poor, with a variety of serious complications, including bone pain, fracture, spinal cord compression and other skeletal related events, affecting the quality of life of patients. At present, radionuclide therapy still has positive clinical effects in patients with bone metastasis, and it still plays an important role in relieving bone pain. This study aimed to evaluate the efficacy of technetium [99Tc] methylene diphosphonate injection (99Tc-MDP) alone or in combination with strontium chloride (89SrCl2) in the treatment of bone metastases. Methods: Databases were used to search for studies published between January 2000 and July 2022 on the efficacy of 99Tc-MDP in combination with 89SrCl2 and 99Tc-MDP alone in the treatment of bone metastases. All included literature was extracted and evaluated for quality, and Meta-analysis was performed using RevMan 5.3 software. Results: Twenty-seven publications met the inclusion criteria, and a total of 2564 patients were included in this study. The results demonstrated that 99Tc-MDP combined with 89SrCl2 improved bone pain relief (RR=1.22, 95% CI: 1.18-1.27, P

Abstract Background Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. Methods Participants aged 65–80 years with a Clinical Frailty Scale of 1–3 points were recruited and followed for 2 years. The eFI score and Fried’s frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan–Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years’ follow-up. Results A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x 2 , p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87–5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44–3.36) for falls; 1.67 (CI: 1.03–2.70) for ER visits; and 2.84 (CI: 1.73–4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried’s scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). Conclusion The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.