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BACKGROUND: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. METHODS: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. RESULTS: In the MR analysis using the inverse variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR=0.046, 95% CI 0.004-0.563, p=0.016). The consistency of findings across maximum likelihood, MR PRESSO, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. CONCLUSIONS: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

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Graphene oxide (GO) is a novel nanomaterial being applied in different fields, but was less used as foliar fertilizer in agriculture. We conducted a pot experiment to analyze the effects of foliar spraying GO from 0 (control), 50 (T1), 100 (T2), 150 (T3) and 200 mg·L-1 (T4) on the morphogenesis and carbon and nitrogen metabolism of kidney bean plants during the initiation of flowering to clarify the physiological effects of foliar spraying GO. The results showed that dry matter accumulation, the content of photosynthetic pigments, soluble sugars of T1 to T4 treatments, were significantly increased by 40.7%-43.4%, 10.4%-80.7%, 6.4%-9.1% in kidney bean plants compared with CK treatment, respectively. T3 treatment performed the best. Meanwhile, the activities of sucrose phosphate synthase, acid converting enzyme and neutral converting enzyme of T3 and T4 treatments were increased by 25.7%-45.5%, 17.4%-28.6%, and 14.7%-20.1%, and the activities of nitrate reductase, glutamine synthetase, and glutamate synthetase of T2 and T3 treatments were increased by 8.1%-15.2%, 11.5%-25.0%, and 89.7%-93.1%, respectively. In conclusion, foliar spraying of appropriate GO in early flowering stage of kidney bean could increase the content of photosynthetic pigments, improve the level of photosynthetic carbon and nitrogen metabolism, and increase dry matter accumulation. T3 treatment (150 mg·L-1) was the most effective in this study.

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BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICUs) and is a common cause of morbidity and mortality in intensive care patients. Previous studies show that insufficient knowledge and compliance barriers among nurses affect pneumonia. There have been no investigations into intensive care nurses' knowledge and compliance barriers to evidence-based guidelines (EBGs) for VAP prevention in county-level hospitals in China. AIMS: To explore adult ICU nurses' knowledge and compliance barriers to EBGs for preventing VAP in county-level hospitals in Hunan Province, China, examine the correlation between knowledge and compliance barriers, and analyse associated factors. STUDY DESIGN: A cross-sectional electronic survey was conducted to focus on nurses' knowledge of and compliance barriers to EBGs for preventing VAP. RESULTS: A total of 386 valid questionnaires were collected, with a response rate of 97.47% (386/396 = 97.47%). The median scores for nurses' knowledge (out of 9) and compliance barriers (out of 8) to EBGs for preventing VAP were 7 (interquartile range: 5-8) and 3 (interquartile range: 2-4), respectively. Knowledge was negatively associated with compliance barriers (r = -0.437, p < .01). The results of the multiple linear regression analysis showed that hospital level, age, nurses' attendance at VAP training and years of experience in ICUs were related to the level of knowledge. Nurses' attendance at VAP training, age and years of experience in ICUs were associated with the level of compliance barriers. CONCLUSIONS: Intensive care nurses have satisfactory knowledge of EBGs for preventing VAP, but compliance barriers can be reduced. Better knowledge helps reduce the barriers to compliance among nurses. RELEVANCE TO CLINICAL PRACTICE: Nurse managers and nurse educators are suggested to examine nurses' knowledge and compliance barriers to EBGs for preventing VAP, develop personalized training plans, promote continuous education based on the latest EBGs and raise the nurse-patient ratio reasonably.

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Facebook, the most popular social media platform in the United States, is used by 239 million US adults, which represents 71% of the population. Not only do most US adults use Facebook but they also spend an average of 40 minutes per day on the platform. Due to Facebook's reach and ease of use, it is increasingly being used as a modality for delivering behavioral and health communication interventions. Typically, a Facebook-delivered intervention involves creating a private group to deliver intervention content for participants to engage with asynchronously. In many interventions, a counselor is present to facilitate discussions and provide feedback and support. Studies of Facebook-delivered interventions have been conducted on a variety of topics, and they vary widely in terms of the intervention content used in the group, use of human counselors, group size, engagement, and other characteristics. In addition, results vary widely and may depend on how well the intervention was executed and the degree to which it elicited engagement among participants. Best practices for designing and delivering behavioral intervention content for asynchronous delivery in Facebook groups are lacking, as are best practices for engaging participants via this modality. In this tutorial, we propose best practices for the use of private Facebook groups for delivery and testing the efficacy of behavioral or health communication interventions, including converting traditional intervention content into Facebook posts; creating protocols for onboarding, counseling, engagement, and data management; designing and branding intervention content; and using engagement data to optimize engagement and outcomes.

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OBJECTIVE: Lifestyle interventions are effective, but those delivered via in-person group meetings have poor scalability and reach. Research is needed to establish if remotely delivered lifestyle interventions are non-inferior to in-person delivered lifestyle interventions. METHODS: We conducted a randomized non-inferiority trial (N = 329) to compare a lifestyle intervention delivered remotely and asynchronously via an online social network (Get Social condition) to one delivered via in-person groups (Traditional condition). We hypothesized that the Get Social condition would result in a mean percent weight loss at 12 months that was not inferior to the Traditional condition. Additional outcomes included intervention delivery costs per pound lost and acceptability (e.g., convenience, support, modality preferences). RESULTS: At 12 months, no significant difference in percent weight change was observed between the Get Social and Traditional conditions (2.7% vs. 3.7%, p = 0.17) however, criteria for non-inferiority were not met. The Get Social condition costs $21.45 per pound lost versus $26.24 for the Traditional condition. A greater percentage of Get Social condition participants rated participation as convenient (65% vs 44%; p = 0.001). CONCLUSIONS: Results revealed a remotely-delivered asynchronous lifestyle intervention resulted in slightly less weight loss than an in-person version but may be more economical and convenient. TRIAL REGISTRATION: ClinicalTrials.gov NCT02646618; https://clinicaltrials.gov/ct2/show/NCT02646618 .

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Enzyme specificity towards cofactors like NAD(P)H is crucial for applications in bioremediation and eco-friendly chemical synthesis. Despite their role in converting pollutants and creating sustainable products, predicting enzyme specificity faces challenges due to sparse data and inadequate models. To bridge this gap, we developed the cutting-edge INSIGHT platform to enhance the prediction of coenzyme specificity in NAD(P)-dependent enzymes. INSIGHT integrates extensive data from principal bioinformatics resources, concentrating on both NADH and NADPH specificities, and utilizes advanced protein language models to refine the predictions. This integration not only strengthens computational predictions but also meets the practical demands of high-throughput screening and optimization. Experimental validation confirms INSIGHT's effectiveness, boosting our ability to engineer enzymes for efficient, sustainable industrial and environmental processes. This work advances the practical use of computational tools in enzyme research, addressing industrial needs and offering scalable solutions for environmental challenges.

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BACKGROUND: The incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because of its relatively straight anatomical structure compared with that of the anterior cerebral arteries. This study aimed to determine the prevalence and characteristics of thrombosis in the posterior-circulation ICAS using OCT. METHODS: This prospective study was conducted on 135 patients with posterior-circulation arterial stenosis who underwent OCT. All patients were symptomatic and had a severely stenotic lesion (70-99%) in the vetebrobasilar artery. The enrolled patients were classified according to the presence of in situ thrombus as defined by OCT. Clinical data and OCT characteristics were compared. RESULTS: Eighty-two patients diagnosed with posterior-circulation ICAS were enrolled. In situ thrombi were identified in 34 patients. Clinically, patients with in situ thrombus were more prone to cerebral infarctions than transient ischemic attacks. The percentage area of stenosis in the non-thrombus group was significantly lower than that in the thrombus group. The thrombus burden, mean flow area, mean thrombus area, maximum lipid arc, and mean lumen area were significantly different among white, red, and mixed thrombi. CONCLUSIONS: We achieved in vivo vessel wall structural analysis of posterior-circulation ICAS with the largest sample size. We also revealed the true incidence of in situ thrombosis and potential corresponding clinical events of posterior-circulation ICAS for the first time.

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Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter. Furthermore, to boost its Pol III activity, we engineered various promoter mutants by introducing mutations or systematically swapping elements. Surprisingly, the Pol II activity of mH1 core mut5 with AT stretch was at least 2-fold greater than that of the wild type, making it a potential candidate for target protein expression purposes. Fortunately, the Pol III activities of mH1 mut1 and mH1 core mut5 were at least 1.5 times stronger than those of the parental promoters in human and mouse cell lines on account of AT stretch, as did the mH1 mut4 with AT stretch and proximal sequence element (PSE) and TATA box insertion mutations. We highly recommend these three promoters as valuable supplements to the type 3 Pol III promoter toolbox.

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Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

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Disulfide bonds, covalently formed by sulfur atoms in cysteine residues, play a crucial role in protein folding and structure stability. Considering their significance, artificial disulfide bonds are often introduced to enhance protein thermostability. Although an increasing number of tools can assist with this task, significant amounts of time and resources are often wasted owing to inadequate consideration. To enhance the accuracy and efficiency of designing disulfide bonds for protein thermostability improvement, we initially collected disulfide bond and protein thermostability data from extensive literature sources. Thereafter, we extracted various sequence- and structure-based features and constructed machine-learning models to predict whether disulfide bonds can improve protein thermostability. Among all models, the neighborhood context model based on the Adaboost-DT algorithm performed the best, yielding "area under the receiver operating characteristic curve" and accuracy scores of 0.773 and 0.714, respectively. Furthermore, we also found AlphaFold2 to exhibit high superiority in predicting disulfide bonds, and to some extent, the coevolutionary relationship between residue pairs potentially guided artificial disulfide bond design. Moreover, several mutants of imine reductase 89 (IR89) with artificially designed thermostable disulfide bonds were experimentally proven to be considerably efficient for substrate catalysis. The SS-bond data have been integrated into an online server, namely, ThermoLink, available at guolab.mpu.edu.mo/thermoLink.

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OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

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Polysaccharides have garnered significant attention as potential nanoparticle carriers for targeted tumor therapy due to their excellent biodegradability and biocompatibility. Polyguluronic acid (PG) is a homogeneous acidic polysaccharide fragment derived from alginate, which is found in brown algae, possesses excellent bioactivities, unique properties. This study explored the immunomodulatory activity of PG and developed PG-based nanogels through modified disulfide bonds and Ca2+ dual crosslinking. We characterized their structure, assessed their drug-loading and release properties, and ultimately validated both the safety of the nanocarrier and the in vitro anti-tumor efficacy of the encapsulated drug. Results indicated that PG significantly enhanced the proliferative activity and phagocytosis of RAW264.7 cells while promoting reactive oxygen species (ROS) production and cytokine secretion. The study identified TLR4 as the primary receptor for PG recognition in RAW264.7 cells. Furthermore, PG-based drug-carrying nanogels were prepared, exhibiting uniform sizes of about 184 nm and demonstrating exceptional encapsulation efficiency (82.15 ± 0.82 %) and drug loading capacity (8.12 ± 0.08 %). In vitro release experiments showed that these nanogels could responsively release drugs under conditions of high glutathione (GSH) reduction, facilitating drug accumulation at tumor sites and enhancing therapeutic efficacy. This research not only expands the application of PG in drug delivery systems but also provides valuable insights into leveraging natural immunomodulatory polysaccharides as carriers for targeted drug delivery.

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Background: Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation. Methods: In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells. Results: In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions. Conclusion: The involvement of PPP4C in LUAD is deeply intertwined with the tumor's immune microenvironment. PPP4C's over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.

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Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.

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Phenamacril (PHA) is a highly selective fungicide for controlling fusarium head blight (FHB) mainly caused by F. graminearum and F. asiaticum. However, the C423A mutation in myosin I of F. graminearum (FgMyoI) leads to natural resistance to PHA. Here, based on the computational approaches and biochemical validation, we elucidate the atomic-level mechanism behind the natural resistance of F. graminearum to the fungicide PHA due to the C423A mutation in FgMyoI. The mutation leads to a rearrangement of pocket residues, resulting in increased size and flexibility of the binding pocket, which impairs the stable binding of PHA. MST experiments confirm that the mutant protein FgMyoIC423A exhibits significantly reduced affinity for PHA compared to wild-type FgMyoI and the nonresistant C423K mutant. This decreased binding affinity likely underlies the development of PHA resistance in F. graminearum. Conversely, the nonresistant C423K mutant retains sensitivity to PHA due to the introduction of a strong hydrogen bond donor, which facilitates stable binding of PHA in the pocket. These findings shed light on the molecular basis of PHA resistance and provide new directions for the creation of new myosin inhibitors.

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Introduction: Salt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial role in enhancing plant resistance to both biotic and abiotic stress. However, a comprehensive understanding of the regulatory mechanisms underlying flavonoid biosynthesis under salt stress in soybean is lacking. Methods: In this study, an integrative analysis of soybean metabolome and transcriptome was conducted using two soybean lines, FQ03 (salt-sensitive, SS) and FQ07 (salt-tolerant, ST). Results: A total of 650 significantly changed metabolites were identified in SS and ST after salt stress treatment. Among them, 151 flavonoids were categorized into nine classes, with flavones and flavonols being the predominant flavonoid types in soybean. Heatmap analysis showed higher contents of most flavonoid metabolites in ST than in SS under salt stress, and the total flavonoid content in ST was significantly higher than that in SS. In addition, transcriptome analysis revealed a higher number of differentially expressed genes (DEGs) in ST than in SS under salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways related to phenylpropanoid biosynthesis, isoflavonoid biosynthesis, flavonoid biosynthesis, as well as flavone and flavonol biosynthesis. Notably, 55 DEGs that were mapped to the flavonoid biosynthetic pathway were identified, with most showing higher expression levels in ST than in SS. Weighted gene correlation network analysis identified eight structural genes and six transcription factor genes as key regulators of flavonoid biosynthesis within the blue module. Furthermore, qRT-PCR results confirmed the accuracy of the transcriptomic data and reliability of the identified candidate genes. Discussion: This study provides insights into the regulatory mechanisms underlying salt stress responses in soybean and highlights hub genes as potential targets for developing salt-tolerant soybean varieties.

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Background: Tumor deposits (TD) was a significant risk factor impacting the prognosis of patients diagnosed with gastric cancer (GC), yet it was not currently incorporated into TNM staging systems. The objective of this research was to develop a predictive model for assessing the prognosis of patients with TD-positive GC. Methods: Retrospective analysis was performed on the data of 4,972 patients treated for GC with D2 radical gastrectomy at Wannan Medical College's Yijishan Hospital between January 2012 and December 2021. The patients were categorized based on the number of TD (L1: 1, L2: 2-3, L3: ≥4) and the anatomical location of TD (Q1: single area, Q2: multiple areas). In a 3:1 ratio, patients were randomly assigned to one of two groups: training or validation. Results: The study included a total of 575 patients who were divided into the training group (n = 432) and validation group (n = 143). Survival analysis showed that the number and anatomical location of TD had a significant impact on the prognosis of patients with TD-positive GC. Univariate analysis of the training group data revealed that tumor size, T-stage, N-stage, histological grade, number and distribution of TD, neural invasion, and postoperative chemotherapy were associated with prognosis. Multivariate Cox regression analysis identified poor histological grade, T4 stage, N3 stage, number of TD, neural invasion, and postoperative chemotherapy as independent prognostic factors for GC patients with TD. A nomogram was developed using these variables, demonstrating well predictive ability for 1, 3, and 5-year overall survival (OS) in the validation set. The DCA curve shows that the constructed model shows a large positive net gain compared to the eighth edition Tumour, Node, Metastasis (TNM) staging system. Conclusion: The prognostic model developed for patients with TD-positive GC has a higher clinical utility compared to the eighth edition of TNM staging.

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PI3K-δ inhibitors have shown impressive activity in lymphoid malignancies but have been hampered by autoimmune and infectious toxicities, leading to market withdrawals. We previously demonstrated activity of the PI3K-δγ inhibitor duvelisib in T cell lymphomas (TCLs) that was associated with inflammatory adverse events. As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n = 66) or bortezomib (n = 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. The primary endpoint of the study was to determine the safety and maximum tolerated dose of duvelisib, which was 75 mg twice daily when combined with romidepsin versus 25 mg twice daily when combined with bortezomib. The most common adverse events were neutropenia (42%, 25/59) and fatigue (37%, 22/59) in patients treated with duvelisib and romidepsin and diarrhea (48%, 11/23) and neutropenia (30%, 7/23) in patients treated with duvelisib and bortezomib. Duvelisib and romidepsin resulted in less grade 3/4 hepatotoxicity (14%, 8/59) compared to 40% (14/35) in our previous study with duvelisib monotherapy. This was associated with reductions in circulating inflammatory mediators and myeloid cell inflammatory gene expression. Secondary endpoints of overall and complete response rates were 55% (35/64) and 34% (22/64) for patients treated with duvelisib and romidepsin and 34% (11/32) and 13% (4/32) for patients treated with duvelisib and bortezomib. Among patients with peripheral T cell lymphomas (PTCLs), overall and complete response rates of duvelisib and romidepsin were 56% (27/48) and 44% (21/48), respectively, with exploratory analyses showing increased response rates in patients with a follicular helper T cell subtype. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625 .

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PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.

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