Global, regional, and national burden of ischemic heart disease attributable to secondhand smoke from 1990 to 2019.

INTRODUCTION: Assessing the burden of ischemic heart disease (IHD) attributable to secondhand smoke (SHS) exposure is crucial for informing evidence-based healthcare practices, prevention strategies, and resource allocation planning. METHODS: The burden of IHD attributable to SHS from 1990 to 2019 was assessed using the comparative risk assessment method as part of the Global Burden of Disease (GBD) study 2019. RESULTS: Globally, the absolute number of deaths and disability-adjusted life-years (DALYs) from IHD due to SHS increased substantially from 270.0 thousand and 6971.3 thousand in 1990 to 397.4 thousand and 9566.1 thousand in 2019. The corresponding age-standardized mortality rates (ASMR) and age-standardized DALYs rates (ASDR) were both in a decreasing trend with estimate of the annual percentage change (EAPC) of -1.38 (-1.42 - -1.34) and -1.43 (-1.47 - -1.38). Central Asia has the highest ASMR (16 per 100000, 95% uncertainty interval, UI: 12.8-19.4), and Oceania has the highest ASDR (323.2 per 100000, 95% UI: 228.9-443.1 per 100000) in 2019. All sociodemographic index (SDI) category regions showed a decreasing trend in ASMR and ASDR, with the decrease being more obvious in high and high-middle SDI regions. Our analysis identified an escalating trend concerning ASMR and ASDR in Oceania from 1990 to 2019. In 2019, the most significant number of deaths and DALYs occurred in the age group of 80-84 years (5.4 thousand, 95% UI: 3.7-7.3 in thousands) and the age group of 55-59 years (1140.8 thousand, 95% UI: 876.1-1435 in thousands). CONCLUSIONS: Our study reveals an absolute global increase in deaths and DALYs from IHD due to SHS from 1990 to 2019. Despite a declining trend in ASMR and ASDR, regional disparities persist. The elderly and middle-aged populations bore the most significant burden. These findings highlight the ongoing global health impact of SHS on IHD and emphasize the need for targeted interventions in regions with rising trends and vulnerable age groups.

The potential of organoids in renal cell carcinoma research.

Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term 'organoids' is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.

Comparison of sea buckthorn fruit oil nanoemulsions stabilized by protein-polysaccharide conjugates prepared using ß-glucan from various sources.

To understand the influence of ß-glucans structure on the emulsifying properties of protein-polysaccharide conjugates, sodium caseinate (NaCas) was utilized to form glycosylation conjugates with varying degrees of glycosylation (10.68-17.50%) using three ß-glucans from bacteria, yeast, and oats. This process induced alterations in the secondary structure of protein. The nanoemulsions prepared with the glycosylated conjugates exhibited superior stability compared to those formulated solely with NaCas, particularly under conditions of drastic pH fluctuations and extended storage periods. The nanoemulsion prepared with the NaCas-Salecan conjugate demonstrated exceptional stability at pH 4 and 6, or storage for 20 days. Additionally, it significantly attenuated the oxidation of unsaturated fatty acids and exhibited the lowest levels of aggregation, flocculation, and free fatty acid release rate during in vitro digestion. This study suggested the potential of the NaCas-Salecan conjugates in enhancing the stability of nanoemulsions and facilitating the colorectal-targeted delivery of sea buckthorn fruit oil.

Pollution sources and risk assessment of potentially toxic elements in soils of multiple land use types in the arid zone of Northwest China based on Monte Carlo simulation.

The concentration of potentially toxic elements (PTEs) in soils of different land-use types varies depending on climatic conditions and human. Topsoil samples were collected in Northwest China to investigate PTE pollution and risk in different land uses, and thereby estimate the risk of various pollution sources. The results showed that human activity had an impact on PTE concentrations in the study area across all land use types, with farmland, grassland, woodland, and the gobi at moderate pollution levels and the desert at light pollution levels. Different PTE sources pose different risks depending on the land-use type. Apart from deserts, children are exposed to carcinogenic risk from a variety of sources. A mixed natural and agricultural source was the main source of public health risk in the study area, contributing 38.7% and 39.0% of the non-carcinogenic and 40.7% and 35.5% of the carcinogenic risks, respectively. Monte Carlo simulations showed children were at a higher health risk from PTEs than adult s under all land uses, which ranked in severity as farmland > woodland > grassland > gobi > desert. As and Ni has a higher probability of posing both a non-carcinogenic and a carcinogenic risk to children. Sensitivity analysis showed that the contribution of parameters to the assessment model of PTEs exhibited the following contribution pattern: concentration > average body weight > ingestion rate > other parameters. The PTEs affecting the risk assessment model were not common among different land use types, where the importance distribution pattern of each parameter was basically the same in woodland, grassland, and farmland, and Ni contributed the most to carcinogenic risk. However, Cr contributed the most to the carcinogenic risk in the desert and gobi.

Determining toxicity of europium oxide nanoparticles in immune cell components and hematopoiesis in dominant organs in mice: Role of lysosomal fluid interaction.

Extensive application of rare earth element oxide nanoparticles (REE NPs) has raised a concern over the possible toxic health effects after human exposure. Once entering the body, REE NPs are primarily processed by phagocytes in particular macrophages and undergo biotic phosphate complexation in lysosomal compartment. Such biotransformation affects the target organs and in vivo fate of REE NPs after escaping the lysosomes. However, the immunomodulatory effects of intraphagolysosomal dissolved REE NPs remains insufficient. Here, europium oxide (Eu2O3) NPs were pre-incubated with phagolysosomal simulant fluid (PSF) to mimic the biotransformation of europium oxide (p-Eu2O3) NPs under acid phagolysosome conditions. We investigated the alteration in immune cell components and the hematopoiesis disturbance on adult mice after intravenous administration of Eu2O3 NPs and p-Eu2O3 NPs. Our results indicated that the liver and spleen were the main target organs for Eu2O3 NPs and p-Eu2O3 NPs. Eu2O3 NPs had a much higher accumulative potential in organs than p-Eu2O3 NPs. Eu2O3 NPs induced more alterations in immune cells in the spleen, while p-Eu2O3 NPs caused stronger response in the liver. Regarding hematopoietic disruption, Eu2O3 NPs reduced platelets (PLTs) in peripheral blood, which might be related to the inhibited erythrocyte differentiation in the spleen. By contrast, p-Eu2O3 NPs did not cause significant disturbance in peripheral PLTs. Our study demonstrated that the preincubation with PSF led to a distinct response in the immune system compared to the pristine REE NPs, suggesting that the potentially toxic effects induced by the release of NPs after phagocytosis should not be neglected, especially when evaluating the safety of NPs application in vivo.

The demethylase ALKBH5 mediates ZKSCAN3 expression through the m6A modification to activate VEGFA transcription and thus participates in MNNG-induced gastric cancer progression.

N-Nitroso compounds (NOCs) are recognized as important factors that promote gastric cancer development, but the specific effects and potential mechanisms by which NOC exposure promotes gastric cancer are still poorly understood. In this study, we explored the effects and potential molecular mechanisms of NOCs on the promotion of gastric cancer using methylnitronitrosoguanidine (MNNG), a classical direct carcinogen of NOC. The results of in vivo and in vitro experiments showed that chronic and low-concentration MNNG exposure significantly promoted the malignant progression of tumors, including cell migration, cell invasion, vasculogenic mimicry (VM) formation, cell spheroid formation, stem cell-like marker expression, and gastric cancer growth and metastasis. Mechanistically, we revealed that demethylase ALKBH5 regulated the level of the N6­methyladenosine (m6A) modification in the 3'UTR and CDS region of the ZKSCAN3 mRNA to promote ZKSCAN3 expression, mediated the binding of ZKSCAN3 to the VEGFA promoter region to regulate VEGFA transcription, and participated in MNNG-induced gastric cancer cell migration, invasion, VM formation, cell spheroid formation, stem cell-like marker expression and ultimately gastric cancer progression. In addition, our study revealed that ALKBH5-ZKSCAN3-VEGFA signaling was significantly activated during MNNG-induced gastric carcinogenesis, and further studies in gastric cancer patients showed that ALKBH5, ZKSCAN3, and VEGFA expression were upregulated in cancers compared with paired gastric mucosal tissues, that ALKBH5, ZKSCAN3, and VEGFA could serve as important biomarkers for determining patient prognosis, and that the molecular combination showed greater prognostic value. These findings provide a theoretical basis for developing gastric cancer interventions for NOCs and for determining gastric cancer progression.

Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.

Background: Prostate cancer (PCa) is one of the most threatening health problems for the elderly males. However, our understanding of the disease has been limited by the research technology for a long time. Recently, the maturity of sequencing technology and omics studies has been accelerating the studies of PCa, establishing themselves as an essential impetus in this field. Methods: We assessed Web of Science (WoS) database for publications of sequencing and omics studies in PCa on July 3rd, 2023. Bibliometrix was used to conduct ulterior bibliometric analysis of countries/affiliations, authors, sources, publications, and keywords. Subsequently, purposeful large amounts of literature reading were proceeded to analyze research hotspots in this field. Results: 3325 publications were included in the study. Research associated with sequencing and omics studies in PCa had shown an obvious increase recently. The USA and China were the most productive countries, and harbored close collaboration. CHINNAIYAN AM was identified as the most influential author, and CANCER RESEARCH exhibited huge impact in this field. Highly cited publications and their co-citation relationships were used to filtrate literatures for subsequent literature reading. Based on keyword analysis and large amounts of literature reading, 'the molecular pathogenesis of PCa' and 'the clinical application of sequencing and omics studies in PCa' were summarized as two research hotspots in the field. Conclusion: Sequencing technology had a deep impact on the studies of PCa. Sequencing and omics studies in PCa helped researchers reveal the molecular pathogenesis, and provided new possibilities for the clinical practice of PCa.

A Bioactive Degradable Composite Bone Cement Based on Calcium Sulfate and Magnesium Polyphosphate.

Calcium sulfate bone cement (CSC) is extensively used as a bone repair material due to its ability to self-solidify, degradability, and osteogenic ability. However, the fast degradation, low mechanical strength, and insufficient biological activity limit its application. This study used magnesium polyphosphate (MPP) and constructed a composite bone cement composed of calcium sulfate (CS), MPP, tricalcium silicate (C3S), and plasticizer hydroxypropyl methylcellulose (HPMC). The optimized CS/MPP/C3S composite bone cement has a suitable setting time of approximately 15.0 min, a compressive strength of 26.6 MPa, and an injectability of about 93%. The CS/MPP/C3S composite bone cement has excellent biocompatibility and osteogenic capabilities; our results showed that cell proliferation is up to 114% compared with the control after 5 days. After 14 days, the expression levels of osteogenic-related genes, including Runx2, BMP2, OCN, OPN, and COL-1, are about 1.8, 2.8, 2.5, 2.2, and 2.2 times higher than those of the control, respectively, while the alkaline phosphatase activity is about 1.7 times higher. Therefore, the CS/MPP/C3S composite bone cement overcomes the limitations of CSC and has more effective potential in bone repair.

S/O/W Emulsion with CAPE Ameliorates DSS-Induced Colitis by Regulating NF-κB Pathway, Gut Microbiota and Fecal Metabolome in C57BL/6 Mice.

Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.

Mechanism of Peptide Self-assembly and Its Study in Biomedicine.

The development of peptide-based materials is one of the most challenging aspects of biomaterials research in recent years. The assembly of peptides is mainly controlled by forces such as hydrogen bonding, hydrophobic interaction, electrostatic interaction, and π-π accumulation. Peptides have unique advantages such as simple structure, easy synthesis, good biocompatibility, non-toxicity, easy modification, etc. These factors make peptides turn into ideal biomedical materials, and they have a broad application prospect in biomedical materials, and thus have received wide attention. In this review, the mechanism and classification of peptide self-assembly and its applications in biomedicine and hydrogels were introduced.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Identification and bioactivity evaluation of ring-opening and lactone forms of enterolactone from sheep fed flaxseed cake.

The previously undescribed lactone ring-opening enterolactone and its sulphate were purified along with the lactone counterparts from the urine of dairy sheep fed flaxseed cake. The structures were determined by NMR and MS analyses. The ring-opening and lactone forms underwent mutual transformation with changes in pH and milk could protect the lactone form. Enterolactone exhibited more effective anti-proliferation activity on MDA-MB-231 breast cancer cells than its ring-opening counterpart, while the ring-opening enterolactone demonstrated more effective anti-osteoporosis activity than the lactone form. The results indicated the potential for targeting biological functions through pH and medium manipulation.

Preoperative prediction of microsatellite instability status: development and validation of a pan-cancer PET/CT-based radiomics model.

OBJECTIVE: The purpose of this study is to verify the feasibility of preoperative prediction of patients' microsatellite instability status by applying a PET/CT-based radiation model. METHODS: This retrospective study ultimately included 142 patients. Three prediction models have been developed. The predictive performance of all models was evaluated by the receiver operating characteristic curve and area under the curve values. The PET/CT radiological histology score (Radscore) was calculated to evaluate the microsatellite instability status, and the corresponding nomogram was established. The correlation between clinical factors and radiological characteristics was analyzed to verify the value of radiological characteristics in predicting microsatellite instability status. RESULTS: Twelve features were retained to establish a comprehensive prediction model of radiological and clinical features. M phase of the tumor has been proven to be an independent predictor of microsatellite instability status. The receiver operating characteristic results showed that the area under the curve values of the training set and the validation set of the radiomics model were 0.82 and 0.75, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the training set were 0.72, 0.78, 0.83 and 0.66, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the validation set were 1.00, 0.50, 0.76 and 1.00, respectively. The risk of patients with microsatellite instability was calculated by Radscore and nomograph, and the cutoff value was -0.4385. The validity of the results was confirmed by the decision and calibration curves. CONCLUSION: Radiological models based on PET/CT can provide clinical and practical noninvasive prediction of microsatellite instability status of several different cancer types, reducing or avoiding unnecessary biopsy to a certain extent.

The efficacy and safety of sacubitril/valsartan in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of natriuretic peptides and inhibiting renin-angiotensin-aldosterone system (RAAS) activation which also relate to the pathophysiologic mechanisms of chronic kidney disease (CKD). However, its effects on CKD remain unclear. To assess the efficacy and safety of sacubitril/valsartan for patients with CKD, we performed this meta-analysis. METHODS: The Embase, PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sacubitril/valsartan with ACEI/ARBs in patients with CKD whose estimated glomerular filtration rate (eGFR) was below 60 mL/min/1.73 m2. We adopted the Cochrane Collaboration tool for assessing the risk of bias. The effect size was estimated using the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Six trials with a total of 6217 patients with CKD were included. In terms of cardiovascular events, sacubitril/valsartan attenuated the risk of cardiovascular death or heart failure hospitalization (OR: 0.68, 95% CI 0.61-0.76, P < 0.00001, I2 = 43%). With respect to renal function, sacubitril/valsartan prevented the incidence of serum creatinine (Scr) elevation among patients with CKD (OR: 0.79, 95% CI 0.67-0.95, P = 0.01, I2 = 0%). Subgroup analysis about eGFR demonstrated that with long follow-up, sacubitril/valsartan significantly decreased the number of patients with more than 50% reduction in eGFR compared with ACEI/ARBs (OR: 0.52, 95% CI 0.32-0.84, P = 0.008, I2 = 9%). In patients with CKD, the incidence of end-stage renal disease (ESRD) was reduced with sacubitril/valsartan treatment, despite no statistically significant difference between the two groups (OR: 0.59, 95% CI 0.29-1.20, P = 0.14, I2 = 0%). As for the safety, we found that sacubitril/valsartan was associated with the occurrence of hypotension (OR: 1.71, 95% CI 1.15-2.56, P = 0.008, I2 = 51%). However, there was no trend towards increasing the risk of hyperkalemia in patients who received sacubitril/valsartan (OR: 1.09, 95% CI 0.75-1.60, P = 0.64, I2 = 64%). CONCLUSION: This meta-analysis indicated that sacubitril/valsartan improved renal function and conferred effective cardiovascular benefits in patients with CKD, without serious safety issues being observed. Thus, sacubitril/valsartan may be a promising option for patients with CKD. Certainly, further large-scale randomized controlled trials are needed to confirm these conclusions. SYSTEMATIC REVIEW REGISTRATION: [ https://inplasy.com/inplasy-2022-4-0045/ ], identifier [INPLASY202240045].

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Role of dynamic contrast-enhanced MRI in predicting severe acute radiation-induced rectal injury in patients with rectal cancer.

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min-1 vs 0.054 min-1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. CONCLUSION: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

MRI-detected tumor deposits in cT3 and cT4 rectal cancer following neoadjuvant chemoradiotherapy.

OBJECTIVES: To evaluate the identification of tumor deposits (TDs) and the prognostic significance of an MRI tumor regression grade for TDs in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: Ninety-one patients with cT3 or cT4 rectal cancer who underwent surgery following nCRT between August 2014 and June 2020 were retrospectively analyzed. Changes in pre-nCRT MRI-detected TDs (mrTDs) were described as mrTD regression grade. The diagnostic performance of post-nCRT MRI-detected TDs (ymrTDs) was compared with histopathological reference standard. The correlation between ymrTDs, mrTD regression grade, and disease-free survival (DFS) was assessed. RESULTS: The sensitivity and specificity of ymrTDs were 88.00% and 89.39%, respectively. The area under the receiver operating characteristic curve was 0.887 (95% confidence interval [CI]: 0.803-0.944). The 3-year DFS of patients with positive ymrTDs was significantly lower than of the negative group (44.83% vs 82.73%, p < 0.001). The 3-year DFS was 33.33% for patients with poor regression of mrTDs following nCRT and 55.56% for those with moderate regression, compared to 69.23% in good responders and 83.97% in patients without mrTDs (p < 0.001). On multivariable Cox regression, mrTD regression grade was the only independent MRI factor associated with DFS (p = 0.042). CONCLUSIONS: Diagnostic performance of ymrTDs was moderate. The mrTD regression grade was independently correlated with DFS, which may have a prognostic implication for treatment and follow-up. CLINICAL RELEVANCE STATEMENT: Patients with poor regression of MRI-detected tumor deposits may benefit from more aggressive treatments, such as chemoradiation therapy plus induction or consolidation chemotherapy. KEY POINTS: • MRI provides a preoperative and noninvasive way to visualize tumor deposits (TDs) after neoadjuvant chemoradiotherapy (nCRT). • Post-nCRT MRI-detected TDs are a poor prognostic marker in cT3 and cT4 rectal cancer patients. • The regression of MRI-detected TDs after nCRT is associated with an improved disease-free survival.

Comparison of cataract patients with regular corneal astigmatism after implantation of extended range-of-vision and bifocal toric intraocular lenses.

Purpose: To compare the postoperative visual acuity and visual quality between extended range-of-vision and multifocal toric intraocular lens (IOLs) after implantation in cataract patients with regular corneal astigmatism. Setting: Department of Ophthalmology, the Second Hospital of Jilin University, Changchun, Jilin Province, China. Design: Retrospective and single-center study. Methods: The study involved implanting the Tecnis Symphony (ZXR00IOL) or the bifocal toric (ZMTIOL) in patients undergoing cataract surgery. Three months after surgery, lens performance was evaluated using distance, intermediate, and near visual acuity tests, defocus curves, the modulation transfer function (MTF), a visual function index questionnaire (VF-14), and the adverse optical interference phenomena. Results: The 3-month postoperative follow-up found that both groups had good corrected distance vision. The ZMT group had better-uncorrected distance visual acuity and near visual acuity (p < 0.05). However, the ZXR group showed better uncorrected intermediate visual acuity (p < 0.05) and visual continuity. Overall astigmatism in the postoperative ZMT group was significantly lower than that in the pre-operative group (p < 0.05). The ZMT group had lower total high-order aberrations (tHOs), higher MTF values, and higher VF-14 scores (p < 0.05). Finally, the ZXR group exhibited reduced halo and glare phenomena (p < 0.05). Conclusion: We found that ZMT can effectively correct a corneal astigmatism of 1.0-1.5 D and ZXR can improve patient outcomes regarding subjective optical quality and range of vision. These findings have the potential to improve future astigmatism treatment options.

Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex.

BACKGROUND: Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms. METHODS: Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a. RESULTS: The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice. CONCLUSIONS: Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.

Purple Yam Polyphenol Extracts Exert Anticolitis and Anticolitis-Associated Colorectal Cancer Effects through Inactivation of NF-κB/p65 and STAT3 Signaling Pathways.

Colorectal cancer is a malignancy with high incidence and mortality worldwide, and ulcerative colitis (UC) is strongly associated with colorectal cancer. Purple yam, also known as Dioscorea alata, has been reported to be rich in plant polyphenols that have possessed anti-inflammatory, antioxidant, and antitumor properties. However, it is not clear whether purple yam polyphenol extracts (PYPE) can improve colitis and inhibit colitis-related colorectal tumorigenesis. Therefore, we used dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer (CAC) models in mice to evaluate the preventive value and possible mechanisms of PYPE. It was found that PYPE effectively alleviated DSS-induced colitis, inhibited macrophage infiltration, and reduced the production of the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, IL-17A, CXCL1, and MCP-1, and the higher the concentration of PYPE, the better the inhibitory effect. In addition, PYPE dramatically prevented the development of CAC and tumor proliferation in mice. Furthermore, PYPE inactivated NF-κB and STAT3 signaling to exert anti-inflammatory and anticancer effects. Taken together, these findings indicate that PYPE may be used as a promising preventive strategy against UC and CAC.