The immunomodulatory mechanism of acupuncture treatment for ischemic stroke: research progress, prospects, and future direction.

Ischemic stroke (IS) is one of the leading causes of death and disability. Complicated mechanisms are involved in the pathogenesis of IS. Immunomodulatory mechanisms are crucial to IS. Acupuncture is a traditional non-drug treatment that has been extensively used to treat IS. The exploration of neuroimmune modulation will broaden the understanding of the mechanisms underlying acupuncture treatment. This review summarizes the immune response of immune cells, immune cytokines, and immune organs after an IS. The immunomodulatory mechanisms of acupuncture treatment on the central nervous system and peripheral immunity, as well as the factors that influence the effects of acupuncture treatment, were summarized. We suggest prospects and future directions for research on immunomodulatory mechanisms of acupuncture treatment for IS based on current progress, and we hope that these will provide inspiration for researchers. Additionally, acupuncture has shown favorable outcomes in the treatment of immune-based nervous system diseases, generating new directions for research on possible targets and treatments for immune-based nervous system diseases.

Trigger a multi-electron reaction by tailoring electronic structure of VO2 toward more efficient aqueous zinc metal batteries.

VO2 (B) is recognized as a promising cathode material for aqueous zinc metal batteries (AZMBs) owing to its remarkable specific capacity and its unique, expansive tunnel structure, which facilitates the reversible insertion and extraction of Zn2+. Nonetheless, challenges such as the inherent instability of the VO2 structure, poor ion/electron transport and a limited capacity due to the low redox potential of the V3+/V4+ couple have hindered its wider application. In this study, we present a strategy to replace vanadium ions by doping Al3+ in VO2. This approach activates the multi-electron reaction (V4+/V5+), to increase the specific capacity and improve the structural stability by forming robust V5+O and Al3+O bonds. It also induces a local electric field by altering the local electron arrangement, which significantly accelerates the ion/electron transport process. As a result, Al-doped VO2 exhibits superior specific capacity, improved cycling stability, and accelerated electronic transport kinetics compared to undoped VO2. The beneficial effects of heterogeneous atomic doping observed here may provide valuable insights into the improvement electrode materials in metal-ion battery systems other than those based on Zn.

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

Online tools to predict individualised survival for primary oesophageal cancer patients with and without pathological complete response after neoadjuvant therapy followed by oesophagectomy: development and external validation of two independent nomograms.

OBJECTIVE: This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy. DESIGN: Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models. RESULTS: In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system. CONCLUSIONS: The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE).

Formation of adequate vascular network within engineered three-dimensional (3D) tissue substitutes postimplantation remains a major challenge for the success of biomaterials-based tissue regeneration. To better mimic the in vivo angiogenic and vasculogenic processes, nowadays increasing attention is given to the strategy of functionalizing biomaterial scaffolds with multiple bioactive agents. Aimed at engineering electrospun biomimicking fibers with pro-vasculogenic capability, this study was proposed to functionalize electrospun fibers of polycaprolactone/gelatin (PCL/GT) by cell-free fat extract (CEFFE or FE), a newly emerging natural "cocktail" of cytokines and growth factors extracted from human adipose tissue. This was achieved by having the electrospun PCL/GT fiber surface coated with polydopamine (PDA) followed by PDA-mediated immobilization of FE to generate the pro-vasculogenic fibers of FE-PDA@PCL/GT. It was found that the PDA-coated fibrous mat of PCL/GT exhibited a high FE-loading efficiency (∼90%) and enabled the FE to be released in a highly sustained manner. The engineered FE-PDA@PCL/GT fibers possess improved cytocompatibility, as evidenced by the enhanced cellular proliferation, migration, and RNA and protein expressions (e.g., CD31, vWF, VE-cadherin) in the human umbilical vein endothelial cells (huvECs) used. Most importantly, the FE-PDA@PCL/GT fibrous scaffolds were found to enormously stimulate tube formation in vitro, microvascular development in the in ovo chick chorioallantoic membrane (CAM) assay, and vascularization of 3D construct in a rat subcutaneous embedding model. This study highlights the potential of currently engineered pro-vasculogenic fibers as a versatile platform for engineering vascularized biomaterial constructs for functional tissue regeneration.

Establishing chronic models of age-related macular degeneration via long-term iron ion overload.

Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW & NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.

Development and preliminary evaluation of the Comprehensive Health Self-Assessment Questionnaire (CHSAQ) for individuals in the Chinese People Liberation Army.

OBJECTIVE: There is currently no widely accepted multidimensional health assessment questionnaire for individuals in the Chinese People Liberation Army (PLA). This study developed a multidimensional health survey questionnaire (Comprehensive Health Self-Assessment Questionnaire, CHSAQ) suitable for personnel in the PLA and conducted a preliminary examination of its reliability, validity, and discriminative ability. METHODS: After 183 items from 32 dimensions were selected to form the initial version of the CHSAQ, three groups of soldiers were selected from May 2022 to April 2023 and completed three survey rounds (with 183, 131, and 55 valid items). The items were screened based on classic test theory. After screening, the final questionnaire entries were formed, the structure of the questionnaire was explored through exploratory factor analysis and confirmatory factor analysis, and its reliability, structural validity, and discriminative ability were evaluated. RESULTS: The final questionnaire consisted of 8 dimensions and 55 items on job satisfaction, anxiety and depression, daily activities, physical function, the otolaryngology system, the integumentary system, sleep disorders, and the visual system. The total cumulative variance contribution rate was 64.648% according to exploratory factor analysis. According to the confirmatory factor analysis, the normed fit index (NFI) was 0.880, and the comparison fit index (CFI) was 0.893 (close to 0.90). The Cronbach's α coefficient of the total questionnaire was 0.970, the split half reliability coefficient was 0.937, and the retest reliability coefficient was 0.902. The results are presented as different pairwise comparisons. CONCLUSION: Our study developed a self-report questionnaire for evaluating the comprehensive health status of personnel in the PLA in accordance with the standard procedure for questionnaire development. Our findings also showed that the CHSAQ for individuals in the PLA has good reliability and structural validity.

Dynamic Changes in Neuroglial Reaction and Tissue Repair after Photothrombotic Stroke in Neonatal Mouse.

Perinatal and neonatal ischemic stroke is a significant cause of cognitive and behavioral impairments. Further research is needed to support models of neonatal ischemic stroke and advance our understanding of the mechanisms of infarction formation following such strokes. We used two different levels of photothrombotic stroke (PTS) models to assess stroke outcomes in neonatal mice. We measured brain damage, dynamic changes in glial cells, and neuronal expression at various time points within two weeks following ischemic injury. Our results from 2,3,5-Triphenyltetrazolium chloride (TTC) staining and immunofluorescence staining showed that in the severe group, a dense border of astrocytes and microglia was observed within 3 days post infarct. This ultimately resulted in the formation of a permanent cortical cavity, accompanied by neuronal loss in the surrounding tissues. In the mild group, a relatively sparse arrangement of glial borders was observed 7 days post infarct. This was accompanied by intact cortical tissue and the restoration of viability in the brain tissue beyond the glial boundary. Additionally, neonatal ischemic injury leads to the altered expression of key molecules such as Aldh1L1 and Olig2 in immature astrocytes. In conclusion, we demonstrated the dynamic changes in glial cells and neuronal expression following different degrees of ischemic injury in a mouse model of PTS. These findings provide new insights for studying the cellular and molecular mechanisms underlying neuroprotection and neural regeneration after neonatal ischemic injury.

Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney.

BACKGROUND: The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250-300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. RESULTS: Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. CONCLUSION: While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.

The influence of resourcefulness on the family functioning of young- and middle-aged lymphoma patients in China: a cross-sectional study.

BACKGROUND: Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. OBJECTIVE: This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. METHODS: A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. RESULTS: The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (ß = 0.338, 95% CI (0.072, 0.173)), spouse caregiver (ß = 0.376, 95% CI (1.938, 10.395)), and cancer stage (ß = -0.274, 95% CI (-3.219, -1.047)). Resourcefulness (ß = 0.438, 95% CI (0.096, 0.181)), spouse caregiver (ß = 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (ß = 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. CONCLUSIONS: Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them.

"Triple-synergistic effect" of K+ and PANI co-intercalation enabling the high-rate capability and stability of V2O5 for aqueous zinc-ion batteries.

Vanadium-based materials are widely recognized as the primary candidate cathode materials for aqueous Zn-ion batteries (AZIBs). However, slow kinetics and poor stability pose significant challenges for widespread application. Herein, to address these issues, alkali metal ions and polyaniline (PANI) are introduced into layered hydrated V2O5 (VO). Density functional theory calculations reveal that the synthesized (C6H4NH)0.27K0.24V2O5·0.92H2O (KPVO), with K+ and PANI co-intercalation, exhibits a robust interlayer structure and a continuous three-dimensional (3D) electron transfer network. These properties facilitate the reversible diffusion of Zn2+ with a low migration potential barrier and rapid response kinetics. The KPVO cathode exhibits a discharge specific capacity of 418.3 mAh/g at 100 mA/g and excellent cycling stability with 89.5 % retention after 3000 cycles at 5 A/g. This work provides a general strategy for integrating cathode materials to achieve high specific capacity and excellent kinetic performance.

Physiological cyclic stretching potentiates the cell-cell junctions in vascular endothelial layer formed on aligned fiber substrate.

In vascular tissue engineering, formation of stable endothelial cell-cell and cell-substrate adhesions is essential for maintaining long-term patency of the tissue-engineered vascular grafts (TEVGs). In this study, sheet-like aligned fibrous substrates of poly(l-lactide-co-caprolactone) (PLCL) were prepared by electrospinning to provide basement membrane-resembling structural support to endothelial cells (ECs). Cyclic stretching at physiological and pathological levels was then applied to human umbilical vein endothelial cells (HUVECs) cultured on chosen fibrous substrate using a force-loading device, from which effects of the cyclic stretching on cell-cell and cell-substrate adhesions were examined. It was found that applying uniaxial 1 Hz cyclic stretch at physiological levels (5 % and 10 % elongation) strengthened the cell-cell junctions, thus leading to improved structural integrity, functional expression and resistance to thrombin-induced damaging impacts in the formed endothelial layer. The cell-cell junctions were disrupted at pathological level (15 % elongation) cyclic stretching, which however facilitated the formation of focal adhesions (FAs) at cell-substrate interface. Mechanistically, the effects of cyclic stretching on endothelial cell-cell and cell-substrate adhesions were identified to be correlated with the RhoA/ROCK signaling pathway. Results from this study highlight the relevance between applying dynamic mechanical stimulation and maintaining the structural integrity of the formed endothelial layer, and implicate a necessity to implement appropriate dynamic mechanical training (i.e., preconditioning) to obtain tissue-engineered blood vessels with long-term patency post-implantation.

Co-doped RuO2 nanoparticles with enhanced catalytic activity and stability for the oxygen evolution reaction.

Efficient and durable electrocatalysts for the oxygen evolution reaction (OER) play an important role in the use of hydrogen energy. Rutile RuO2, despite being considered as an advanced electrocatalyst for the OER, performs poorly in stability due to its easy oxidative dissolution at very positive (oxidizing) potentials. Herein, we report a type of Co-doped RuO2 nanoparticle for boosting OER catalytic activity and stability in alkaline solutions. The replacement of Ru by Co atoms with a lower ionic valence and smaller electronegativity can promote the generation of O vacancies and increase the electron density around Ru, thus enhancing the adsorption of oxygen species and inhibiting the peroxidative dissolution of RuO2 during the OER process. It was found that Ru0.95Co0.05Oy exhibited excellent OER performance with overpotentials as low as 217 mV at 10 mA cm-2 and 290 mV at 100 mA cm-2 in 1 M KOH, as well as outstanding stability in continuous testing for 50 h at a current density of 100 mA cm-2, and nearly no significant degradation after the accelerated durability test of 2000 cycles.

Preoperative CT Radiomics Nomogram for Predicting Microvascular Invasion in Stage I Non-Small Cell Lung Cancer.

RATIONALE AND OBJECTIVES: This study aims to develop and validate a nomogram integrating clinical-CT and radiomic features for preoperative prediction of microvascular invasion (MVI) in patients with stage I non­small cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study analyzed 188 cases of stage I NSCLC (63 MVI positives and 125 negatives), which were randomly assigned to training (n = 133) and validation cohorts (n = 55) at a ratio of 7:3. Preoperative non-contrast and contrast-enhanced CT (CECT) images were used to analyze computed tomography (CT) features and extract radiomics features. The student's t-test, the Mann-Whitney-U test, the Pearson correlation, the least absolute shrinkage and selection operator, and multivariable logistic analysis were used to select the significant CT and radiomics features. Multivariable logistic regression analysis was performed to build the clinical-CT, radiomics, and integrated models. The predictive performances were evaluated through the receiver operating characteristic curve and compared with the DeLong test. The integrated nomogram was analyzed regarding discrimination, calibration, and clinical significance. RESULTS: The rad-score was developed with one shape and four textural features. The integrated nomogram incorporating radiomics score, spiculation, and the number of tumor-related vessels (TVN) demonstrated better predictive efficacy than the radiomics and clinical-CT models in the training cohort (area under the curve [AUC], 0.893 vs 0.853 and 0.828, and p = 0.043 and 0.027, respectively) and validation cohort (AUC, 0.887 vs 0.878 and 0.786, and p = 0.761 and 0.043, respectively). The nomogram also demonstrated good calibration and clinical usefulness. CONCLUSION: The radiomics nomogram integrating the radiomics with clinical-CT features demonstrated good performance in predicting MVI status in stage I NSCLC. The nomogram may be a useful tool for physicians in improving personalized management of stage I NSCLC.

Divergence of trafficking and polarization mechanisms for PIN auxin transporters during land plant evolution.

The phytohormone auxin, and its directional transport through tissues, plays a fundamental role in the development of higher plants. This polar auxin transport predominantly relies on PIN-FORMED (PIN) auxin exporters. Hence, PIN polarization is crucial for development, but its evolution during the rise of morphological complexity in land plants remains unclear. Here, we performed a cross-species investigation by observing the trafficking and localization of endogenous and exogenous PINs in two bryophytes, Physcomitrium patens and Marchantia polymorpha, and in the flowering plant Arabidopsis thaliana. We confirmed that the GFP fusion did not compromise the auxin export function of all examined PINs by using a radioactive auxin export assay and by observing the phenotypic changes in transgenic bryophytes. Endogenous PINs polarize to filamentous apices, while exogenous Arabidopsis PINs distribute symmetrically on the membrane in both bryophytes. In the Arabidopsis root epidermis, bryophytic PINs have no defined polarity. Pharmacological interference revealed a strong cytoskeletal dependence of bryophytic but not Arabidopsis PIN polarization. The divergence of PIN polarization and trafficking is also observed within the bryophyte clade and between tissues of individual species. These results collectively reveal the divergence of PIN trafficking and polarity mechanisms throughout land plant evolution and the co-evolution of PIN sequence-based and cell-based polarity mechanisms.

Association of clonal haematopoiesis with severe postoperative complications in patients undergoing radical oesophagectomy.

BACKGROUND: Clonal haematopoiesis (CH) is an age-associated clonal expansion of blood cells driven by leukaemia-associated somatic mutations. Although CH has been reported to be a risk factor for leukaemia and a number of non-haematopoietic diseases, its role in perioperative medicine remains unexplored. METHODS: This was a single-centre, prospective, observational study. Patients undergoing radical oesophagectomy were enrolled, and peripheral blood samples were collected for DNA sequencing. Patients with haematopoietic somatic mutations (variant allele frequencies ≥1%) in the DNMT3A gene, TET2 gene, or both were defined as CH carriers. The primary outcome was the incidence of severe postoperative complications (Clavien-Dindo classification ≥3). The secondary outcomes included the major types of postoperative complications, mortality, and other common perioperative variables. RESULTS: Clonal haematopoiesis was found in 21.2% (33/156) of the patients (mean age: 66 yr [range: 26-79 yr]; 83% males). Some 14/33 (42.4%) patients with CH had severe postoperative complications, compared with patients without CH carriers (28/123 [22.8%]; P=0.024). Multivariable logistic regression analysis showed that CH was associated with an increased risk of developing severe postoperative complications (odds ratio, 3.63; 95% confidence interval, 1.37-9.66; P=0.010). Among the major postoperative complications, the incidence of pulmonary complications was significantly higher in the patients with CH than in those without CH (15 in 33 [45.5%] vs 30 in 123 [24.4%], P=0.018). CONCLUSIONS: Clonal haematopoiesis was associated with a higher incidence of severe postoperative complications in patients undergoing radical oesophagectomy, suggesting that clonal haematopoiesis can play an important role in perioperative medicine. CLINICAL TRIAL REGISTRATION: ChiCTR2100044175 (Chinese Clinical Trial Registry, http://www.chictr.org.cn/showproj.aspx?proj=123193).

Identification of Optimal Parameters for Assessing Lymph Node Status of Patients with Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND: This study aimed to compare the prognostic discrimination power of pretreatment pathologic N stage (prepN), lymph node tumor regression grade (LNTRG), and posttreatment pathologic N (ypN) category for esophageal squamous cell carcinoma (ESCC) patients who received neoadjuvant chemoradiotherapy (nCRT) plus surgery. METHODS: The study reviewed 187 ESCC patients from two medical centers who underwent nCRT plus surgery. Pathologic LNTRG was defined by the proportion of viable tumor area within the tumor bed in lymph nodes (LNs). An average LNTRG then was calculated by averaging the tumor regression grade (TRG) score of all resected LNs. Lymph nodes containing regression changes or vital tumor cells were used for interpretation of the prepN stage, which reflects the estimated number of originally involved LNs. RESULTS: The ypN, prepN, and LNTRG categories had significant prognostic stratification power (p < 0.001, log-rank test). Multivariable cox regression showed that all three categories were independent prognostic factors of disease-free survival (DFS) (p < 0.05). The LNTRG category showed a better prognostic value for DFS prediction than the ypN and prepN categories (Akaike information criterion [AIC]: LNTRG [933.69], ypN [937.56], prepN [937.45]). Additionally, the superior predictive capacity of the LNTRG category was demonstrated by decision curve analysis. Similar results were discovered for patients with remaining diseased LNs. CONCLUSIONS: The three staging categories had prognostic relevance for DFS, with the LNTRG category seeming to have better prognostic indication power. Comprehensive consideration of the ypN status, prepN status, and LN regression may allow for better prognostic stratification of patients.

Two-dimensional multifunctional nanosheets as radiosensitizers for chemodynamic/radio-therapy.

The hypoxia tumor microenvironment and low radiation attenuation coefficient of tumor tissue usually limit the efficiency of radiotherapy. In this study, a two-dimensional multifunctional nano-sensitizer, CuNS@Pt, was prepared to function as a radiosensitizer, enhancing radiotherapy through multiple mechanisms. Numerous active sites were provided for the deposition of X-ray radiation energy by the in-situ chemical reduction of Pt to create functional hybrids on Cu-based nanosheets. CuNS@Pt catalyzed high concentration of endogenous hydrogen peroxide to generate oxygen in tumor microenvironment, alleviating the physiological environment of hypoxic tumors. Additionally, CuNS could reduce the content of intrinsic glutathione (GSH) and catalyze hydrogen peroxide to form hydroxyl radicals (·OH). The generated ·OH could damage mitochondria and destroy redox homeostasis due to the functional inclusion of Cu species, thereby achieving chemodynamic therapy and further improving the radiation effect. Both in vivo and in vitro experiments showed that the nano sensitizer effectively improved the therapeutic efficiency of radiotherapy and had good biological safety. All in all, this study provides a pragmatic and doable platform for maximizing the efficacy of RT in cancer. This study also highlights the future research value of two-dimensional nanomaterials.

Multifunctional AuPt Nanoparticles for Synergistic Photothermal and Radiation Therapy.

Background: Photothermal therapy (PTT) has gained considerable interest as an emerging modality for cancer treatment in recent years. Radiation therapy (RT) has been widely used in the clinic as a traditional treatment method. However, RT and PTT treatments are limited by side effects and penetration depth, respectively. In addition, hypoxia within the tumor can lead to increased resistance to treatment. Methods: We synthesized multiple sizes of AuPt by modulating the reaction conditions. The smallest size of AuPt was selected and modified with folic acid (FA) for PTT and RT synergy therapy. Various methods including transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FITR) are used to determine the structure and composition of AuPt-FA (AF). In addition, we researched the photothermal properties of AF with IR cameras and infrared lasers. Flow cytometry, colony formation assays, CCK8, and fluorescent staining for probing the treatment effect in vitro. Also, we explored the targeting of AF by TEM and In Vivo Imaging Systems (IVIS). In vivo experiments, we record changes in tumor volume and weight as well as staining of tumor sections (ROS, Ki67, and hematoxylin and eosin). Results: The AuPt with particle size of 16 nm endows it with remarkably high photothermal conversion efficiency (46.84%) and catalase activity compared to other sizes of AuPt (30 nm and 100 nm). AF alleviates hypoxia in the tumor microenvironment, leading to the production of more reactive oxygen species (ROS) during the treatment. In addition, the therapeutic effect was significantly enhanced by combining RT and PTT, with an apoptosis rate of 81.1% in vitro and an in vivo tumor volume reduction rate of 94.0% in vivo. Conclusion: These results demonstrate that AF potentiates the synergistic effect of PTT and RT and has the potential for clinical translation.