Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review.

Regulatory T cells (Tregs) expressing the transcription factor FoxP3 are essential for maintaining immunological balance and are a significant component of the immunosuppressive tumor microenvironment (TME). Single-cell RNA sequencing (ScRNA-seq) technology has shown that Tregs exhibit significant plasticity and functional diversity in various tumors within the TME. This results in Tregs playing a dual role in the TME, which is not always centered around supporting tumor progression as typically believed. Abundant data confirms the anti-tumor activities of Tregs and their correlation with enhanced patient prognosis in specific types of malignancies. In this review, we summarize the potential anti-tumor actions of Tregs, including suppressing tumor-promoting inflammatory responses and boosting anti-tumor immunity. In addition, this study outlines the spatial and temporal variations in Tregs function to emphasize that their predictive significance in malignancies may change. It is essential to comprehend the functional diversity and potential anti-tumor effects of Tregs to improve tumor therapy strategies.

Arabidopsis cryptochrome 1 controls photomorphogenesis through regulation of H2A.Z deposition.

Light is a key environmental cue that fundamentally regulates plant growth and development, which is mediated by the multiple photoreceptors including the blue light (BL) photoreceptor cryptochrome 1 (CRY1). The signaling mechanism of Arabidopsis thaliana CRY1 involves direct interactions with CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1)/SUPPRESSOR OF PHYA-105 1 and stabilization of COP1 substrate ELONGATED HYPOCOTYL 5 (HY5). H2A.Z is an evolutionarily conserved histone variant, which plays a critical role in transcriptional regulation through its deposition in chromatin catalyzed by SWR1 complex. Here we show that CRY1 physically interacts with SWC6 and ARP6, the SWR1 complex core subunits that are essential for mediating H2A.Z deposition, in a BL-dependent manner, and that BL-activated CRY1 enhances the interaction of SWC6 with ARP6. Moreover, HY5 physically interacts with SWC6 and ARP6 to direct the recruitment of SWR1 complex to HY5 target loci. Based on previous studies and our findings, we propose that CRY1 promotes H2A.Z deposition to regulate HY5 target gene expression and photomorphogenesis in BL through the enhancement of both SWR1 complex activity and HY5 recruitment of SWR1 complex to HY5 target loci, which is likely mediated by interactions of CRY1 with SWC6 and ARP6, and CRY1 stabilization of HY5, respectively.

Quantitative proteomic analysis reveals the mechanism and key esterase of ß-cypermethrin degradation in a bacterial strain from fermented food.

Beta-cypermethrin (ß-CY) residues in food are an important threat to human health. Microorganisms can degrade ß-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of ß-CY in a food microorganism was conducted based on proteomics analysis. The ß-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of ß-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of ß-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of ß-CY, which confirmed that this enzyme was the key enzyme in the process of ß-CY degradation. This study reveals the degradation mechanism of ß-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in ß-CY residues.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

Enhancing the Quality of Low-Alcohol Navel Orange Wine through Simultaneous Co-Fermentation Using Saccharomyces cerevisiae SC-125, Angel Yeast SY, and Lactiplantibacillus plantarum BC114.

To date, there has been limited research on the interactive effects of yeast and lactic acid bacteria (LAB) on the sensory qualities of navel orange wine. In this study, using Jintang navel orange juice as the raw material, multi-microbial fermentation was conducted with Saccharomyces cerevisiae SC-125 and Angel yeast SY, as well as Lactiplantibacillus plantarum BC114. Single yeast and co-fermentation with Lactiplantibacillus plantarum were used as the control groups. The research aimed to investigate the physicochemical parameters of navel orange wine during fermentation. Additionally, headspace solid-phase microextraction gas chromatography-mass spectrometry (HP-SPME-GC-MS) was employed to determine and analyze the types and levels of flavor compounds in the navel orange wines produced through the different fermentation methods. The co-fermentation using the three strains significantly enhanced both the quantity and variety of volatile compounds in the navel orange wine, concomitant with heightened total phenol and flavonoid levels. Furthermore, a notable improvement was observed in the free radical scavenging activity. A sensory evaluation was carried out to analyze the differences among the various navel orange wines, shedding light on the impact of different wine yeasts and co-fermentation with LAB on the quality of navel orange wines.

Survival outcomes in locally advanced dMMR rectal cancer: surgery plus adjunctive treatment vs. surgery alone.

BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.

Adsorption Mechanism of Benzene Derivatives by Pagoda[n]arenes.

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment. The control of these substances has become an important subject of scientific research. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing pagoda[n]arene based supramolecular materials. Density functional theory calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes (Pa[4]As and Pa[5]As). Results indicate that Pa[4]As and Pa[5]As can effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]As possess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivatives to desorb from the adsorbing aggregates, and thus the material can be reutilized.

Reclassification of Sabulilitoribacter multivorans and Sabulilitoribacter arenilitoris as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov., respectively, based on genome sequence analysis.

Rapid advancements in DNA sequencing technologies are providing new approaches for bacterial taxonomy. The genus Sabulilitoribacter is a member of the family Flavobacteriaceae, which consists of more than 150 genera. In this study, genome sequence analysis was conducted to revisit the taxonomic status of Sabulilitoribacter arenilitoris and Sabulilitoribacter multivorans, the only two species of this genus. Genome sequence based phylogeny analysis showed that the genus Sabulilitoribacter was non-monophyletic: S. multivorans, the type species of genus Sabulilitoribacter, was clustered with the type species of the genus Flaviramulus, whereas S. arenilitoris formed a robust cluster with the only two species of the genus Wocania. The values of average amino acid identity, genome-wide average nucleotide identity, alignment fractions and some phenotypic features showed that S. multivorans was more closely related with the type species of the genus Flaviramulus than with S. arenilitoris, and S. arenilitoris was more closely related with the only two species of the genus Wocania than with S. multivorans. Based on these results, we consequently propose that S. multivorans and S. arenilitoris should be reclassified as Flaviramulus multivorans comb. nov. and Wocania arenilitoris comb. nov. respectively.

Prioritizing conservation efforts based on future habitat availability and accessibility under climate change.

The potential for species to shift their ranges to avoid extinction is contingent on the future availability and accessibility of habitats with analogous climates. To develop conservation strategies, many previous researchers used a single method that considered individual factors; a few combined 2 factors. Primarily, these studies focused on identifying climate refugia or climatically connected and spatially fixed areas, ignoring the range shifting process of animals. We quantified future habitat availability (based on species occurrence, climate data, land cover, and elevation) and accessibility (based on climate velocity) under climate change (4 scenarios) of migratory birds across the Yangtze River basin (YRB). Then, we assessed species' range-shift potential and identified conservation priority areas for migratory birds in the 2050s with a network analysis. Our results suggested that medium (i.e., 5-10 km/year) and high (i.e., ≥ 10 km/year) climate velocity would threaten 18.65% and 8.37% of stable habitat, respectively. Even with low (i.e., 0-5 km/year) climate velocity, 50.15% of climate-velocity-identified destinations were less available than their source habitats. Based on our integration of habitat availability and accessibility, we identified a few areas of critical importance for conservation, mainly in Sichuan and the middle to lower reaches of the YRB. Overall, we identified the differences between habitat availability and accessibility in capturing biological responses to climate change. More importantly, we accounted for the dynamic process of species' range shifts, which must be considered to identify conservation priority areas. Our method informs forecasting of climate-driven distribution shifts and conservation priorities.

Priorizar los esfuerzos de conservación en función de la disponibilidad y accesibilidad futura de hábitats ante el cambio climático Resumen El potencial de las especies para desplazar sus rangos y evitar la extinción depende de la disponibilidad y accesibilidad futura de hábitats con climas análogos. Para desarrollar estrategias de conservación, muchos investigadores anteriores utilizaron un solo método que consideraba factores individuales; algunos combinaron 2 factores. Principalmente, estos estudios se centraron en identificar refugios climáticos o áreas climáticamente conectadas y espacialmente fijas, ignorando el proceso de desplazamiento de rangos de los animales. Cuantificamos la disponibilidad futura de hábitats (basada en la presencia de especies, datos climáticos, cobertura terrestre y elevación) y la accesibilidad (basada en la velocidad climática) bajo el cambio climático (4 escenarios) de aves migratorias en la cuenca del río Yangtsé (YRB). Luego, evaluamos el potencial de desplazamiento de rangos de las especies e identificamos áreas prioritarias de conservación para las aves migratorias en la década de 2050 mediante un análisis de redes. Nuestros resultados sugieren que una velocidad climática media (es decir, 5−10 km/año) y alta (es decir, ≥ 10 km/año) amenazarían el 18.65% y el 8.37% del hábitat estable, respectivamente. Incluso con una velocidad climática baja (es decir, 0−5 km/año), el 50.15% de los destinos identificados por la velocidad climática eran menos disponibles que sus hábitats de origen. Basándonos en nuestra integración de la disponibilidad y accesibilidad de hábitats, identificamos algunas áreas de importancia crítica para la conservación, principalmente en Sichuan y en las partes media e inferior del YRB. En general, identificamos las diferencias entre la disponibilidad y accesibilidad de hábitats en la captura de respuestas biológicas al cambio climático. Más importante aún, tuvimos en cuenta el proceso dinámico de los desplazamientos de rangos de especies, lo cual debe considerarse para identificar áreas prioritarias de conservación. Nuestro método contribuye a la predicción de cambios en la distribución impulsados por el clima y las prioridades de conservación.

The comparison of risk factors for colorectal neoplasms at different anatomical sites.

AIM: Both the clinical manifestation and molecular characteristics of colorectal cancer (CRC) vary according to the anatomical site. We explored the risk factors for four groups of colorectal neoplasms (CRN) at different anatomical sites. METHODS: We extracted data from the database of Tianjin Colorectal Cancer Screening Program from 2010 to 2020. According to the CRN anatomical sites, patients were divided into four groups: the proximal colon group, the distal colon group, the rectum group, and the multiple colorectal sites. Binary logistic regression analysis was used to explore the differences in risk factors of CRN at different anatomical sites. RESULTS: The numbers of patients with CRN in the proximal colon, distal colon, rectum, and multiple colorectal sites were 4023, 6920, 3657, and 7938, respectively. Male sex was associated with a higher risk from the proximal colon to the rectum. Advanced age and obesity were also significantly associated with overall colorectal CRN risk, but there were some differences between men and women. Smoking was associated with CRN risk only in the distal colon and rectum in both men and women. Frequent alcohol consumption and family history of CRC in first-degree relatives (FDRs) were associated with the risk of multisite colorectal CRN only in males. CONCLUSIONS: We observed differences in advanced age, obesity, smoking, alcohol consumption, and family history of colorectal cancer at different anatomical sites of colorectal neoplasms. These factors vary by gender.

Colonoscopy compliance and diagnostic yield in a large population-based colorectal cancer screening programme.

OBJECTIVES: With the intention of providing a reference for secondary prevention, our study provides some insight on diagnostic yield of factors influencing compliance with colonoscopy and the presence of advanced adenomas (AA). METHODS: We conducted large-scale CRC screening among local Tianjin residents aged 40-75 years between 2012 and 2019. A high-risk factor questionnaire (HRFQ) was distributed to each participant, followed by the performance of a fecal immunochemical test (FIT). Participants who tested positively for any of these items were advised to undergo a colonoscopy. Relevant basic information was collected from participants during CRC screening, and the screening data were sorted and analysed. RESULTS: A total of 5,670,924 people participated in CRC screening by the end of 2019, including 275,708 people in the high-risk group, and 74,685 (27.1%) people who underwent colonoscopy. The results of the logistic regression model demonstrated that participants with a history of mucous bloody stool (OR = 8.20, 95% CI: 7.92, 8.50, p < 0.001), chronic diarrhea (OR = 5.73, 95% CI: 5.57, 5.89, p < 0.001), and higher level of education (OR = 1.87, 95% CI: 1.80, 1.93, p < 0.001) were more likely to comply with a colonoscopy. Several factors including age (70-75 years old:OR = 3.72, 95% CI: 2.71, 5.10, p < 0.001), and FIT( +) (OR = 1.65, 95% CI: 1.42,1.90, p < 0.001) were identified to be associated with the presence of AA. CONCLUSIONS: Increased compliance with colonoscopy is urgently needed. Our findings can inform the design of future effective large-scale population-based CRC screening programmes.

The accuracy of the FIT in detecting advanced neoplasm is highest in young people aged 40 to 49 years: an analysis based on sex and age.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age. METHODS: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age. RESULTS: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40-49, 50-59, 60-69, and ≥ 70 age groups, respectively. CONCLUSIONS: The FIT detected ANs with highest accuracy in the 40-49 age group. Our research can provide guidance to formulate CRC screening strategies.

Droj2 Facilitates Somatosensory Neurite Sculpting via GTP-Binding Protein Arf102F in Drosophila.

Developmental remodeling of neurite is crucial for the accurate wiring of neural circuits in the developing nervous system in both vertebrates and invertebrates, and may also contribute to the pathogenesis of neuropsychiatric disorders, for instance, autism, Alzheimer's disease (AD), and schizophrenia. However, the molecular underpinnings underlying developmental remodeling are still not fully understood. Here, we have identified DnaJ-like-2 (Droj2), orthologous to human DNAJA1 and DNAJA4 that is predicted to be involved in protein refolding, as a developmental signal promoting dendrite sculpting of the class IV dendritic arborization (C4da) sensory neuron in Drosophila. We further show that Arf102F, a GTP-binding protein previously implicated in protein trafficking, serves downstream of Droj2 to govern neurite pruning of C4da sensory neurons. Intriguingly, our data consistently demonstrate that both Droj2 and Arf102F promote the downregulation of the conserved L1-type cell-adhesion molecule Neuroglian anterior to dendrite pruning. Mechanistically, Droj2 genetically interacts with Arf102F and promotes Neuroglian downregulation to initiate dendrite severing. Taken together, this systematic study sheds light on an unprecedented function of Droj2 and Arf102F in neuronal development.

The Protective Effect of Auricularia cornea var. Li. Polysaccharide on Alcoholic Liver Disease and Its Effect on Intestinal Microbiota.

This study's objective was to examine the protective effect and mechanism of a novel polysaccharide (AYP) from Auricularia cornea var. Li. on alcoholic liver disease in mice. AYP was extracted from the fruiting bodies of Auricularia cornea var. Li. by enzymatic extraction and purified by DEAE-52 and Sephacryl S-400. Structural features were determined using high-performance liquid chromatography, ion exchange chromatography and Fourier-transform infrared analysis. Additionally, alcoholic liver disease (ALD) mice were established to explore the hepatoprotective activity of AYP (50, 100 and 200 mg/kg/d). Here, our results showed that AYP presented high purity with a molecular weight of 4.64 × 105 Da. AYP was composed of galacturonic acid, galactose, glucose, arabinose, mannose, xylose, rhamnose, ribos, glucuronic acid and fucose (molar ratio: 39.5:32.9:23.6:18.3:6.5:5.8:5.8:3.3:2:1.1). Notably, AYP remarkably reduced liver function impairment (alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC)), nitric oxide (NO) and malondialdehyde (MDA) of the liver and enhanced the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (gGSH)) in mice with ALD. Meanwhile, the serum level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were reduced in ALD mice treated by AYP. Furthermore, the AYPH group was the most effective and was therefore chosen to further investigate its effect on the intestinal microbiota (bacteria and fungi) of ALD mice. Based on 16s rRNA and ITS-1 sequencing data, AYP influenced the homeostasis of intestinal microbiota to mitigate the damage of ALD mice, possibly by raising the abundance of favorable microbiota (Muribaculaceae, Lachnospiraceae and Kazachstania) and diminishing the abundance of detrimental microbiota (Lactobacillus, Mortierella and Candida). This discovery opens new possibilities for investigating physiological activity in A. cornea var. Li. and provides theoretical references for natural liver-protecting medication research.

Phylogenomics and evolutionary history of Oreocnide (Urticaceae) shed light on recent geological and climatic events in SE Asia.

Climate change and geological events have long been known to shape biodiversity, implying that these can likewise be viewed from a biological perspective. To study whether plants can shed light on this, and how they responded to climate change there, we examined Oreocnide, a genus widely distributed in SE Asia. Based on broad geographic sampling with genomic data, we employed an integrative approach of phylogenomics, molecular dating, historical biogeography, and ecological analyses. We found that Oreocnide originated in mainland East Asia and began to diversify ∼6.06 Ma, probably in response to a distinct geographic and climatic transition in East Asia at around that time, implying that the last important geological change in mainland SE Asia might be 1 Ma older than previously suggested. Around six immigration events to the islands of Malesia followed, indicating that immigration from the mainland could be an underestimated factor in the assembly of biotic communities in the region. Two detected increases of diversification rate occurred 3.13 and 1.19 Ma, which strongly implicated climatic rather than geological changes as likely drivers of diversification, with candidates being the Pliocene intensification of the East Asian monsoons, and Pleistocene climate and sea level fluctuations. Distribution modelling indicated that Pleistocene sea level and climate fluctuations were inferred to enable inter-island dispersal followed by allopatric separation, underpinning radiation in the genus. Overall, our study, based on multiple lines of evidence, linked plant diversification to the most recent climatic and geological events in SE Asia. We highlight the importance of immigration in the assembly and diversification of the SE Asian flora, and underscore the utility of plant clades, as independent lines of evidence, for reconstructing recent climatic and geological events in the SE Asian region.

Effects of deficient mismatch repair on the prognosis of patients with stage II and stage III colon cancer during different postoperative periods.

BACKGROUND: We evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy. METHODS: This retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods. RESULTS: The median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years. CONCLUSION: The benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.

Mismatch repair system deficiency is associated with chemoradiotherapy resistance in locally advanced rectal adenocarcinoma patients.

BACKGROUND AND OBJECTIVES: Previous studies have concluded that colorectal cancer patients with deficient mismatch repair (dMMR) usually have a good prognosis. However, some studies have suggested that the prognosis of rectal cancer patients with dMMR appears to be worse. Our aim was to investigate chemoradiotherapy resistance in dMMR rectal tumors. METHODS: A retrospective study of 217 patients with locally advanced rectal adenocarcinoma treated with chemoradiotherapy and total mesorectal excision surgery was conducted using immunohistochemistry to determine MMR status and propensity score matching models to reduce potential confounders. Kaplan-Meier analysis, log-rank test, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: The 3-year DFS rates were 77.1% and 56.7% in the pMMR and dMMR groups, respectively. The pMMR group had significantly better DFS than the dMMR group (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.10-3.91; p = 0.019). However, there was no significant difference in OS between the two groups (45.7 [interquartile range, IQR], 39.3-72.1] vs. 47.5 [IQR, 29.5-72.1]) (HR, 1.39; 95% CI, 0.70-2.77; p = 0.35). Neither OS nor DFS was significantly different between the neoadjuvant chemoradiotherapy and postoperative chemoradiotherapy groups. CONCLUSION: Locally advanced dMMR rectal adenocarcinoma exhibits greater chemoradiotherapy resistance than pMMR.

Topography and etiologies of cerebellar infarcts presenting as isolated acute vestibular syndrome.

BACKGROUND AND PURPOSE: To investigate the topography and etiologies of acute cerebellar infarcts (ACIs) that presented as isolated acute vestibular syndromes (AVSs). METHODS: ACI was ascertained on magnetic resonance diffusion-weighted imaging combined with apparent diffusion coefficient sequence and was categorized into the simple (territory and small infarct) and the complicated (concomitant infarcts in territories of posterior circulation besides cerebellum). Infarct topography and etiologies were compared between ACI patients with isolated AVS and non-isolated AVS (general and/or local neurological symptoms and/or signs with or without AVS). RESULTS: We enrolled 129 ACI patients, and 53 patients (53/129, 41.1%) had isolated AVS. In isolated AVS, the infarct lesions could be territory infarcts, small infarcts involving cortical, subcortical, and areas directly related to vestibular structures, and the primary etiologies were of large artery atherosclerosis and small vessel disease. Compared with the patients with non-isolated AVS, those with isolated AVS had more prevalence of small vessel disease (OR 6.30, 2.16-18.39; p = 0.001) and more probability of small infarcts (OR 6.04, 95%CI 2.31-15.76; p < 0.0001). In isolated AVS patients, the small infarct located more frequently in cerebellar hemispheres than the areas directly related to vestibular structures (27/35 vs 8/35), and the territory infarct located more frequently in the area supplied by posterior inferior cerebellar artery than the other areas (9/13 vs 4/13). CONCLUSION: Our study found that ACI could be presented as isolated AVS, which occurred more frequently in patients with small hemisphere infarct or infarct in the territory supplied by posterior inferior cerebellar artery.

The risk factors of old silent brain infarctions in carotid artery stenosis.

BACKGROUND AND PURPOSE: This study aims to investigate the risk factors of old ipsilateral silent brain infarctions (iSBIs) in patients with internal carotid artery (ICA) stenosis. METHODS: Consecutive patients with unilateral ICA stenosis ≥ 50% or occlusion were retrospectively enrolled. Old iSBIs were assessed on magnetic resonance imaging. Baseline characteristics and imaging features were compared between patients with and without iSBIs. Multivariable regression analysis was conducted to identify independent risk factors of iSBIs. RESULTS: We enrolled 274 patients with unilateral ICA stenosis ≥ 50% or occlusion. One hundred thirty-three patients had iSBIs to stenosed ICA (48.54%). One hundred thirty-seven patients had recent brain infarction on either side (50.0%). The patients with iSBIs had a lower level of high-density lipoprotein [OR 0.60, 95% CI (0.36-0.96), P = 0.045], higher prevalence of irregular/ulcer plaque [OR 10.71, 95% CI (4.60-24.95), P < 0.0001], and incompleteness of circle of Willis [OR 0.27, 95% CI (0.16-0.45), P < 0.0001] in all enrolled patients. In the patients without recent infarction on either side, lower level of high-density lipoprotein [OR 0.42, 95% CI (0.27-0.88), P = 0.031], higher prevalence of irregular/ulcer plaque [OR 12.73, 95% CI (4.13-39.22), P < 0.0001] and incompleteness of circle of Willis [OR 0.24, 95% CI (0.11-0.50), P = 0.004] were independently associated with iSBIs. The results were similar in ICA stenosis patients with recent brain infarction on either side. CONCLUSION: In patients with carotid stenosis, incompleteness of circle of Willis, irregular/ulcer plaque, and lower level of high-density lipoprotein were independently associated with old iSBIs.

Circulating Methylated SEPT9 DNA Analyses to Predict Recurrence Risk and Adjuvant Chemotherapy Benefit in Stage II to III Colorectal Cancer.

BACKGROUND We aimed to evaluate the ability of circulating cell-free methylated SETP9 DNA (mSEPT9) to identify recurrence and to determine its clinical utility in adjuvant chemotherapy (ACT) regimen decisions. MATERIAL AND METHODS This study enrolled 426 patients with stage II-III CRC who received radical resection between January 8, 2018, and November 30, 2020. The median follow-up duration was 15.8 months (range, 8.1-43.4 months). The primary endpoint was recurrence-free survival (RFS). A propensity score matching model was used to minimize potential confounding covariates and to confirm our findings. RESULTS In stage II-III CRC patients, postoperative (within 1 month after surgery) mSEPT9 positivity was significantly correlated with worse RFS (HR=6.21, P<0.001), and it remained the strongest independent predictor in multivariate Cox regression analysis (HR=5.83, P<0.001), which was significantly superior to CEA, CA19-9, and CA242. During disease surveillance, mSEPT9 positivity preceded radiographic recurrence by a median of 5.0 months. The postoperative mSEPT9-positive patients benefited more from CAPEOX compared to FOLFOX (HR=3.97, P=0.017), while for mSEPT9-negative patients, CAPEOX and FOLFOX resulted in similar RFS (HR=1.70, P=0.322). Furthermore, 3 months of CAPEOX was more effective than 3 and 6 months of FOLFOX (HR=4.40, P=0.065; HR=1.56, P=0.073, respectively). CONCLUSIONS Our results revealed that mSEPT9 detection after radical resection could identify minimal residual disease (MRD) and could predict a high risk of recurrence in patients with stage II-III CRC. Furthermore, we show pioneering work that mSEPT9 detection could be used to guide the selection of an adjuvant chemotherapy regimen to improve RFS.