Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

A surviving neonate with congenitally unguarded tricuspid valve orifice.

The hospital admitted a 3-day-old female infant presenting with persistent facial cyanosis and hypoxic symptoms, and echocardiography revealed a congenitally unguarded tricuspid valve orifice with an atrial septal defect. After being followed up until the age of one and a half years, the child underwent bidirectional Glenn's surgery and achieved successful survival.

Performance of radiomics in the differential diagnosis of parotid tumors: a systematic review.

Purpose: A systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy. Methods: Databases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model. Results: A total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions. Conclusion: There is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

Assessment of left atrial function provides incremental value: the left atrial volumetric/mechanical coupling index in patients with chronic kidney disease.

Background: Heart failure is a common cause of adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Left atrial (LA) characteristics are thought to be involved in the development of heart failure. However, LA assessment is complex. Though a variety of parameters have been defined, there is no single parameter that best defines LA function. Pilot data indicate that left atrial volumetric/mechanical coupling index (LACI) may be useful, but data with CKD are lacking. Aim: The objective of this study was to define LACI in a cohort of patients with CKD and to assess its value in evaluating LA function and predicting heart failure. Methods: A cohort of patients with CKD was enrolled at our hospital between 2021 and 2023. Follow-up was performed for heart failure. LACI is a volumetric to mechanical coupling index, calculated as the ratio of the LA volume index to the tissue-Doppler myocardial velocity at atrial contraction. Spearman's rank correlation or Pearson's correlation was used to calculate the correlation between LACI and echocardiographic/hemodynamic variables. Receiver operating characteristic curve (ROC) analysis was utilised to derive the area under the curve (AUC) for LACI, LVGLS, LASr, LASct and LASI for the detection of heart failure. Kaplan-Meier survival curves were employed to compare clinical outcomes based on LACI thresholds. A multivariable logistic regression analysis was employed to assess the relationship between risk factors and elevated LACI. Cox proportional hazards regression was used to identify risk factors for heart failure. Results: LACI showed a positive correlation with NT-proBNP, CK-MB, LAVI, E/e' and LASI (r = 0.504, 0.536, 0.856, 0.541 and 0.509, p < 0.001); and a negative correlation with LASr (r = -0.509, p < 0.001). On the ROC analysis for the determination of heart failure, the AUC of LACI was comparable to those of LVGLS (0.588 vs. 509, p = 0.464), LASr (0.588 vs. 0.448, p = 0.132), LASct (0.588 vs. 0.566, p = 0.971) and LASI (0.588 vs. 0.570, p = 0.874). The cardiovascular risk factors increased by LACI were age, BMI, diabetes, triglycerides, LA size, LASr, LASI, E/A, E/e' and EF (p < 0.05). During a median follow-up of 16 months (range, 6-28 months), the event-free survival curves demonstrated a higher risk of heart failure in the group with LACI > 5.0 (log-rank test: P < 0.001). LACI > 5.0 was an independent predictor of heart failure [OR: 0.121, 95% CI (0.020-0.740), p = 0.022]. Conclusion: LACI may prove to be a valuable tool for assessing LA function in patients with CKD, and could be integrated into the routine assessment of LA for the purpose of prognostic assessment and clinical decision-making in patients with CKD.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review.

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.

Accessing 1,8-Naphthyridone-3-carboxylic Acid Derivatives and Application to the Synthesis of Amfonelic Acid.

1,8-Naphthyridone-3-carboxyl is the core structure of several on-market antibacterial drugs. It has prompted significant interest from the synthetic community. Here, we report a practical synthesis of diversely functionalized 1,8-naphthyridone-3-carboxylic acid derivatives starting from readily available and inexpensive nicotinic acid derivatives. All key steps have been optimized. Furthermore, the usefulness of this protocol has been exemplified by the first synthesis of amfonelic acid.

Development of monoclonal antibodies targeting the conserved fragment of hexon protein to detect different serotypes of human adenovirus.

Human adenovirus (HAdV) infects the respiratory system, thus posing a threat to health. However, immunodiagnostic reagents for human adenovirus are limited. This study aimed to develop efficient diagnostic reagents based on monoclonal antibodies for diagnosing various human adenovirus infections. Evolutionary and homology analyses of various human adenoviral antigen genes revealed highly conserved antigenic fragments. The prokaryotic expression system was applied to recombinant penton, hexon, and IVa2 conserved fragments of adenovirus, which were injected into BALB/c mice to prepare human adenovirus-specific monoclonal antibodies. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blotting were used to determine the immune specificity of the monoclonal antibodies. Indirect ELISA showed that monoclonal antibodies 1F10, 8D3, 4A1, and 9B2 were specifically bound to HAdV-3 and HAdV-55 and revealed high sensitivity and low detection limits for various human adenoviruses. Western blotting showed that 1F10 and 8D3 specifically recognized various human adenovirus types, including HAdV-1, HAdV-2, HAdV-3, HAdV-4, HAdV-5, HAdV-7, HAdV-21, and HAdV-55, and 4A1 specifically recognized HAdV-1, HAdV-2, HAdV-3, HAdV-5, HAdV-7, HAdV-21, and HAdV-55. IFAs showed that 1F10, 8D3, and 4A1 exhibited highly selective localization to A549 cells infected with HAdV-3 and HAdV-55. Finally, two antibody pairs that could detect hexon antigens HAdV-3 and HAdV-55 at low concentrations were developed. The monoclonal antibodies developed in this study show potential for detecting human adenoviruses. IMPORTANCE: In this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.

Distinct clinical characteristics in stage III rectal cancer among different age groups and treatment outcomes after neoadjuvant chemoradiotherapy.

Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633-4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720-5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102-4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145-4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113-2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150-3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745-4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282-3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS (p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS (p = 0.006, p = 0.018, p = 0.006, respectively). Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.

[Corrigendum] Azurocidin 1 inhibits the aberrant proliferation of triple­negative breast cancer through the regulation of pyroptosis.

Following the publication of the above article, the authors drew to our attention that they had made a couple of inadvertent errors in assembling Figs. 4 and 5; first, for the BT­549 cell line, the data shown for the Pro­caspase­1/Cleaved caspase­1 in Fig. 5 and the GSDMD­F/GSDMD­N data in Fig. 4B were identical, and had been derived from the same original source; secondly, in Fig. 4A, the data shown correctly for the GSDMD BT­549 cell line had also inadvertently been included in this figure to represent the MDA­MB­231 cell line. The revised and corrected versions of Figs. 4 and 5, showing the correct western blotting data for the GSDMD experiment in Fig. 4A and the Pro­caspase­1/Cleaved caspase­1 data for the BT­549 cell line in Fig. 5, are shown in the next two pages. The authors regret that these errors in the assembly of Figs. 4 and 5 went unnoticed before the article was published, and thank the Editor of Oncology Reports for granting them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership of the journal for any inconvenience caused.[Oncology Reports 50: 188, 2023; DOI: 10.3892/or.2023.8625].

Toward a low carbon path: Do E-commerce reduce CO2 emissions? Evidence from China.

To address global climate change, achieving carbon peak and carbon neutrality has become a global consensus. However, the means to simultaneously achieve carbon reduction and promote green economic development, particularly in developing countries, require further investigation. This study evaluates the impact of e-commerce on CO2 emissions. Through an examination of the effects of the National E-Commerce Demonstration City (NEDC) policy from 2006 to 2017, this paper reveals that e-commerce growth facilitated by the NEDC policy resulted in a 7.89% reduction in total CO2 emissions and a per capita reduction of 1.1146 tons in the pilot cities. Mechanism analysis demonstrates that the upgrading of industrial structure, development of digital finance, and the growth of innovation and entrepreneurship serve as primary pathways for this impact. The robustness of the findings is supported by parallel trend tests, placebo tests, and additional sensitivity analyses. Furthermore, the research reveals that the NEDC policy exhibits a more significant reduction in CO2 emissions in cities with higher levels of economic development and non-resource-based cities. Welfare analyses show that the NEDC policy has significant socio-economic effects. These findings provide new evidence on the environmental effects of the digital economy and offer insights into achieving carbon neutrality.

Non-high-density lipoprotein cholesterol levels as a risk factor for short-term mortality in elderly Chinese: a large-scale, population-based cohort study.

OBJECTIVES: To explore the association between non-high-density lipoprotein (non-HDL) and mortality risk, both short-term and long-term, in Chinese people. DESIGN: A prospective cohort study. SETTING: The National Basic Public Health Service (BPHS) in China. PARTICIPANTS: Including 621 164 elderly individuals around Hunan Province who underwent healthcare management receiving check-ups in China BPHS from 2010 to 2020. EXCLUSION CRITERIA: (1) missing information on gender; (2) missing records of lipid screening; (3) missing information on key covariates; and (4) missing records of comorbidities (cardiovascular disease, hypertension, diabetes, cancer.) PRIMARY AND SECONDARY OUTCOME MEASURES: The study's primary endpoint was all-cause and cause-specific mortality, sourced from Hunan's CDC(Center for Disease Control and Prevention)-operated National Mortality Surveillance System, tracking participants until 24 February 2021. RESULTS: 26 758 (4.3%) deaths were recorded, with a median follow-up of 0.83 years. Association between non-HDL and mortality was non-linear after multivariable adjustment, with the optimum concentration (OC) being 3.29 and 4.85 mmol/L. Compared with OC, the risk increased by 1.12-fold for non-HDL <3.29 mmol/L (HR: 1.12 (1.09 to 1.15)) and 1.08-fold for non-HDL ≥4.85 mmol/L (HR: 1.08 (1.02 to 1.13)) for all-cause mortality. Furthermore, there is also an increased risk of cardiovascular mortality (HR for non-HDL <3.29: 1.10 (1.06 to 1.32) and HR for non-HDL ≥4.85: 1.07 (1.01 to 1.14)). However, cancer mortality risk was significantly increased only for non-HDL <3.29 mmol/L (HR: 1.11 (1.04 to 1.18)). Non-optimum concentration of non-HDL had significant effects on both the long-term and the short-term risk of mortality, especially for risks of mortality for all-cause (log HR:0 .086 (0.038 to 0.134)), cardiovascular (log HR:0 .082 (0.021 to 0.144)), and cancer (log HR:0 .187 (0.058 to 0.315)) within 3 months. A two-sided value of p <0.05 was considered to be statistically significant. CONCLUSIONS: Non-HDL was non-linearly associated with the risk of mortality, and non-optimal concentrations of non-HDL significantly increased short-term mortality in elderly Chinese, which needs more attention for cardiovascular disease prevention.

RAMP1 as a novel prognostic biomarker in pan-cancer and osteosarcoma.

Receptor activity modifying protein 1 (RAMP1) facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane, but its role in osteosarcoma (OS) remains unclear. We evaluated the RAMP1 expression and prognostic value across different cancers, studying tumor immune infiltration. The prognostic value was analyzed using the GSE39058 and TARGET datasets. Differential gene expression was evaluated. a protein-protein interaction network was constructed, and gene set enrichment analysis was performed. The function of RAMP1 in the tumor microenvironment was analyzed, and its expression in OS cell lines was validated using quantitative real-time PCR. High RAMP1 expression correlated with poor prognosis relative to low RAMP1 expression (p < 0.05). Low RAMP1 expression correlated with an abundance of CD4+ memory-activated T cells. whereas a high expression level correlated with a high proportion of gamma-delta T cells (γδ T cells). Differentially expressed genes from TARGET was enriched in olfactory transduction pathways (normalized enrichment scores [NES] = 1.6998, p < 0.0001). RAMP1 expression negatively correlated with CD44 expression but positively correlated with TNFSF9 expression. The RAMP1 gene is substantially expressed in OS cells compared to the normal osteoblast cell line hFOB1.19. Thus, RAMP1 may be a prognostic biomarker and potential therapeutic target in OS.

Mesenchymal stem cell-derived exosomal miR-548x-3p inhibits pyroptosis of vascular endothelial cells through HMGB1 in heat stroke.

Heat stroke (HS) is an acute physical illness associated with a higher risk of organ dysfunction. This study is the first to explore exosomal miR-548x-3p derived from human bone marrow mesenchymal stem cells (BMSCs) in the pyroptosis of vascular endothelial cells (VECs) associated with HS. Human BMSCs-derived exosome alleviated the injury of the heart, liver, kidney and ileum tissues, the increase of IL-1ß, IL-18 and TNF-α levels, pyroptosis of endothelial cells and the increase of HGMB1, NLRP3, ASC, caspase1 and GSDMD-N protein expression in HS mice and HS-induced human umbilical vein endothelial cells (HUVECs). miR-548x-3p was down-expressed in HS patients, while up-expressed in BMSCs-derived exosome. BMSCs-ExomiR-548x-3p mimics to inhibit pyroptosis, inflammation and HGMB1/NLRP3 activation in HS-induced HUVECs and HS mice, which were blocked by overexpression of HMGB1. In conclusion, human BMSCs-derived exosomes carried miR-548x-3p mimics to inhibit pyroptosis of VECs through HMGB1 in HS mice.

Azurocidin 1 inhibits the aberrant proliferation of triple­negative breast cancer through the regulation of pyroptosis.

Azurocidin 1 (AZU1) is a heparin­binding protein which has been reported to be aberrantly expressed in various tumors, but its definite role in breast cancer (BC) has not been clarified. The aim of the present study was to explore the associations between AZU1 and BC. In the present study, bioinformatics and western blot analyses were applied to detect the expression level of AZU1 in BC tissues. The effect of AZU1 on cell proliferation and apoptosis was analyzed using Cell Counting Kit­8 assay, colony formation assay and flow cytometry. Based on bioinformatics analysis, AZU1 exhibited low expression in tissues and was negatively associated with the survival rate of patients with triple­negative BC (TNBC). Exogenous AZU1 stimuli significantly inhibited the proliferation and colony formation of TNBC cell lines. Furthermore, the data of flow cytometry revealed that exogenous AZU1 stimuli enhanced apoptosis in MDA­231 and BT­549 cells. As pyroptosis is a new type of cell death, the effects AZU1 played on the expression of gasdermin D (GSDMD), a specific biomarker of pyroptosis, were also investigated. The findings of the present study revealed that GSDMD, as well as its upstream regulators [NF­κB, NLR family pyrin domain containing 3 (NLRP3) and caspase­1], were significantly increased in TNBC cell lines when treated with exogenous AZU1, indicating that AZU1 contributed to the inhibition of pyroptosis of TNBC cell lines through the NF­κB/NLRP3/caspase­1 axis. Collectively, it was revealed for the first time, that AZU1 exposure promoted pyroptosis through the modulation of the pNF­κB/NLRP3/caspase­1/GSDMD axis in TNBC in vitro. The findings of the present study unveiled a novel mechanism of AZU1­induced pyroptosis in TNBC, which may aid in developing new strategies for therapeutic interventions in TNBC. breast cancer is the most commone form of cancer in women and is second only to lung cancer in terms of cancer­related mortality.

3D Elastomeric Stent Functionalized with Antioxidative and Perivascular Tissue Regenerative Activities Ameliorated PVT Deprivation-Induced Vein Graft Failure.

Clinically, arterial injuries are always accompanied with perivascular tissue damage, which may contribute to high failure rate of vein grafts due to intimal hyperplasia and acute thrombosis. In this study, a "perivascular tissue (PVT) deprivation" animal model is constructed to mimic clinical scenarios and identify the contribution of arterial PVT to the success of vein grafts. Proteomics analysis suggests that depriving PVT may exacerbate reactive oxygen species (ROS)-induced endothelial apoptosis by up-regulating inflammation response and oxidative stress. Locally administering metformin on vein grafts through 3D-printed external stent (PGS-PCL) shows antioxidative and anti-inflammatory properties to protect cells from ROS invasion, thereafter decreasing acute thrombosis. Moreover, metformin induce rapid regeneration of perivascular adipose tissue in recipient regions, which improves patency by inhibiting intimal hyperplasia. Proteomics, western blot, and in vitro blocking tests reveal that metformin resists endothelial apoptosis through AMPK/mTOR and NFκB signaling pathways. To conclude, PVT deprivation exacerbates inflammatory response and oxidative stress in vein grafts bridging arterial circulation. Metformin-loaded stent ameliorates "PVT damage" related vein graft failure, and enhances patency of through resisting endothelial apoptosis and regenerating arterial PVAT, offering a promising avenue to improve the success of vein grafts in clinic.

Metagenomic Analysis of Intratumoral Microbiome Linking to Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

PURPOSE: To assess taxonomic and functional characteristics of tumor-bearing microbiota and its association with response to neoadjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: We performed metagenomic sequencing of biopsy tumoral tissues from 73 patients with locally advanced rectal cancer before nCRT. Patients were classified into poor responders (PR) and good responders (GR) according to response to nCRT. Subsequent investigation of network alteration, key community, microbial biomarkers, and function related to nCRT responses were carried out. RESULTS: The network-driven analysis systematically revealed 2 co-occurring bacteria modules that exhibited opposite relationship with rectal cancer radiosensitivity. In the 2 modules, prominent alteration of global graph properties and community structure was observed between networks of PR and GR group. By quantifying changes in between-group association patterns and abundances, a total of 115 discriminative biomarker species linked to nCRT response were found, and 35 microbial variables were selected to establish the optimal randomForest classifier for nCRT response prediction. It yielded an area under the curve value of 85.5% (95% CI, 73.3%-97.8%) in the training cohort and 88.4% (95% CI, 77.5%-99.4%) in the validation cohort. In a comprehensive consideration, 5 key bacteria showed high relevance with inducing resistance to nCRT, including Streptococcus equinus, Schaalia odontolytica, Clostridium hylemonae, Blautia producta, and Pseudomonas azotoformans. One key hub including several butyrate-formation bacteria involving with driving network alteration from GR to PR indicate that microbiota-derived butyrate may also be involved in reducing the antitumor effects of nCRT, especially Coprococcus. The functional analysis of metagenome linked the nitrate and sulfate-sulfur assimilation, histidine catabolic process, and resistance to cephamycin to the reduced therapeutic response. It also linked to leucine degradation, isoleucine biosynthesis, taurine, and hypotaurine metabolism to the improved response to nCRT. CONCLUSIONS: Our data offer novel potential microbial factors and shared metagenome function linked to resistance to nCRT.

Intraparotid lymph node metastasis affects distant metastasis in parotid adenoid cystic carcinoma.

To evaluate the relationship between factors of metastatic intraparotid lymph node (IPLN) and distant metastasis in parotid adenoid cystic carcinoma (ACC). Patients with surgically treated parotid ACC were retrospectively enrolled, and primary outcome variable was distant metastasis free survival (DMFS). The effect of factors of metastatic IPLN on DMFS was evaluated using Cox model. In total, 232 patients were included. Extranodal extension of IPLN and cervical lymph nodes did not impact the DMFS, and the 7th but not 8th AJCC N stage was associated with DMFS. Groups of 0 and 1 metastatic IPLN had comparable DMFS, but presence of 2+ positive IPLN was related to increased worse DMFS (p = 0.034, HR 2.09). A new N stage (0 vs 1-2 vs 3+) based on total positive lymph node number exhibited better C-index than traditional N stage. IPLN metastasis increased the risk of distant metastasis, and the impact was mainly determined by the number of metastatic IPLN. Our proposed N stage provided better DMFS prediction than the 8th AJCC N classification.