The prognostic value of lymph node to primary tumor standardized uptake value ratio in cancer patients: a meta-analysis.

OBJECTIVE: The lymph node to primary tumor standardized uptake value ratio (NTR) is an innovative parameter derived from positron emission tomography/computed tomography (PET/CT) scans that captures the intricate relationship between primary tumors and associated lymph nodes. This meta-analysis aimed to investigate the prognostic value of NTR in cancer patients. METHODS: A systematic search of PubMed, Cochrane, and Embase databases was conducted to identify studies investigating the association between NTR and survival outcomes in cancer patients. The pooled adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twelve studies comprising a total of 2037 patients were included in the meta-analysis. Elevated NTR was significantly associated with worse overall survival aHR (2.21, 95% CI 1.63 to 2.99), disease-free survival aHR (3.27, 95% CI 2.12 to 5.05), and distant metastasis-free survival aHR (2.07, 95% CI 1.55 to 2.78) in cancer patients. Subgroup analyses by cancer type showed consistent results across various malignancies, including head and neck squamous cell carcinoma, endometrial carcinoma, lung cancer, breast cancer, and nasopharyngeal carcinoma. CONCLUSIONS: This meta-analysis provides evidence for a significant association between elevated NTR and worse survival outcomes in cancer patients. Elevated NTR may serve as a useful prognostic biomarker for cancer patients and could potentially be used to guide treatment decisions and monitor disease progression. Future studies should aim to validate these findings in larger and more diverse patient populations and investigate the underlying mechanisms for the observed association between NTR and survival outcomes.

Development of a dual point humidity sensor using POF based on twisted fiber structure.

The humidity has often been measured through a single point sensor. Where, the humidity could be varied at different locations as well as depending on environmental conditions. The present paper developed the dual point humidity measuring sensor by using a polymer optical fiber (POF) based on a single illuminating fiber. The sensor's basic structure is to twist two fibers and bend them at a certain radius. However, the dual point sensor is developed through the cascading of twisted micro bend (TMB-1 and TMB-2). The twisting of fibers couples the light from one fiber to another fiber through the side coupling method. An increase in the humidity level leads to a change in the reflective index, which helps to get variation in coupled light intensity. To measure the humidity, the dual point sensors are placed into the control humidity chamber at two random positions. The power reading variation is significantly linear when the humidity level increases from 30 to 80%. The sensor has a fast response of about 1 s and a recovery time of about 4 s. Furthermore, the chemical coating is applied to improve the sensor's sensitivity. Between 30 and 80% range of humidity, the both sensors of dual point TMB-1 and TMB-2 have appropriate sensitivity and detection limits, which is about 680.8 nW/% and 763.9 nW/% and 1.37% and 1.98%, respectively. To measure the humidity at variable positions, the present dual points humidity sensor is well-stable, easy, and straightforward, which uses a less expensive method.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

FedDUS: Lung tumor segmentation on CT images through federated semi-supervised with dynamic update strategy.

BACKGROUND AND OBJECTIVE: Lung tumor annotation is a key upstream task for further diagnosis and prognosis. Although deep learning techniques have promoted automation of lung tumor segmentation, there remain challenges impeding its application in clinical practice, such as a lack of prior annotation for model training and data-sharing among centers. METHODS: In this paper, we use data from six centers to design a novel federated semi-supervised learning (FSSL) framework with dynamic model aggregation and improve segmentation performance for lung tumors. To be specific, we propose a dynamically updated algorithm to deal with model parameter aggregation in FSSL, which takes advantage of both the quality and quantity of client data. Moreover, to increase the accessibility of data in the federated learning (FL) network, we explore the FAIR data principle while the previous federated methods never involve. RESULT: The experimental results show that the segmentation performance of our model in six centers is 0.9348, 0.8436, 0.8328, 0.7776, 0.8870 and 0.8460 respectively, which is superior to traditional deep learning methods and recent federated semi-supervised learning methods. CONCLUSION: The experimental results demonstrate that our method is superior to the existing FSSL methods. In addition, our proposed dynamic update strategy effectively utilizes the quality and quantity information of client data and shows efficiency in lung tumor segmentation. The source code is released on (https://github.com/GDPHMediaLab/FedDUS).

Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.

BACKGROUND: Although oncogenic RAS mutants are thought to exert mutagenic effects upon blood cells, it remains uncertain how a single oncogenic RAS impacts non-transformed multipotent hematopoietic stem or progenitor cells (HPCs). Such potential pre-malignant status may characterize HPCs in patients with RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD). This study sought to elucidate the biological and molecular alterations in human HPCs carrying monoallelic mutant KRAS (G13C) with no other oncogene mutations. METHODS: We utilized induced pluripotent stem cells (iPSCs) derived from two unrelated RALD patients. Isogenic HPC pairs harboring either wild-type KRAS or monoallelic KRAS (G13C) alone obtained following differentiation enabled reliable comparative analyses. The compound screening was conducted with an established platform using KRAS (G13C) iPSCs and differentiated HPCs. RESULTS: Cell culture assays revealed that monoallelic KRAS (G13C) impacted both myeloid differentiation and expansion characteristics of iPSC-derived HPCs. Comprehensive RNA-sequencing analysis depicted close clustering of HPC samples within the isogenic group, warranting that comparative studies should be performed within the same genetic background. When compared with no stimulation, iPSC-derived KRAS (G13C)-HPCs showed marked similarity with the wild-type isogenic control in transcriptomic profiles. After stimulation with cytokines, however, KRAS (G13C)-HPCs exhibited obvious aberrant cell-cycle and apoptosis responses, compatible with "dysregulated expansion," demonstrated by molecular and biological assessment. Increased BCL-xL expression was identified amongst other molecular changes unique to mutant HPCs. With screening platforms established for therapeutic intervention, we observed selective activity against KRAS (G13C)-HPC expansion in several candidate compounds, most notably in a MEK- and a BCL-2/BCL-xL-inhibitor. These two compounds demonstrated selective inhibitory effects on KRAS (G13C)-HPCs even with primary patient samples when combined. CONCLUSIONS: Our findings indicate that a monoallelic oncogenic KRAS can confer dysregulated expansion characteristics to non-transformed HPCs, which may constitute a pathological condition in RALD hematopoiesis. The use of iPSC-based screening platforms will lead to discovering treatments that enable selective inhibition of RAS-mutated HPC clones.

EZH2 Promotes Multiple Myeloma Progression via STAT3 Pathway Activation.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder of plasma cells in the bone marrow. MM causes the clonal proliferation of terminally differentiated plasma cells and the accumulation of monoclonal plasma cells. The enhancer of zeste homolog 2 (EZH2) has been proven to play a significant role in disease development and could act on the signal transducers and activators of the transcription 3 (STAT3) signaling pathway. This pathway contributes to the pathogenesis and maintenance of malignancies. This study aimed to explore the effect of EZH2 on MM progression and the role of the STAT3 pathway in this process. The goal was to increase knowledge and provide further insights about the pathogenesis of MM and identify novel targets for potential therapies. METHODS: The abnormal expression of EZH2 in MM cell lines was tested through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot analysis. Based on the MM cell line H929, transfection was used to modify EZH2 expression, followed by the subsequent evaluation of induced alteration in STAT3 activation. The STAT3 phosphorylation activator colivelin and inhibitor stattic were used for promoting and inhibiting the STAT3 activation, respectively. Colony-forming assay, transwell migration assay, and flow cytometry were used to explore cell proliferation, cell migration, and cell apoptosis, respectively. RESULTS: Both the EZH2 mRNA and protein were over-expressed in multiple MM cell lines including H929 (p < 0.001), U266 (p < 0.01), RPMI-8226 (p < 0.01) and MM.1S (p < 0.001). Increased EZH2 promoted cell proliferation (p < 0.001) and migration (p < 0.001) and simultaneously inhibited cell apoptosis (p < 0.001), which could be reversed by inhibited STAT3 activation (p < 0.001). In contrast, promoted STAT3 activation increased cell proliferation (p < 0.001) and migration (p < 0.001), while simultaneously inhibiting cell apoptosis (p < 0.001), despite decreased EZH2 expression. CONCLUSIONS: The effect of EZH2 and STAT3 pathways on MM regulation was revealed and verified. EZH2 promoted the progression of MM cells by activating the STAT3 pathway. The EZH2 and STAT3 pathways could be potential targets for effective MM treatment.

Alleviative effects of sulfated polysaccharide from Ishige Okamurae against DSS-induced ulcerative colitis via inhibiting inflammation and modulating gut microbiota.

A water-soluble polysaccharide from the brown alga Ishige Okamurae, designated IOP-0, was obtained by preparative anion-exchange and size-exclusion chromatography. Chemical and spectroscopic investigations revealed that IOP-0 was a sulfated fucoidan with a backbone primarily composed of 3-linked and 4-linked-L-fucose with sulfate groups at C-2/C-4 of the 3-linked-L-fucose. The protective effect of IOP-0 on ulcerative colitis was evaluated in this work. The results showed that IOP-0 could significantly alleviate the symptoms of ulcerative colitis by preventing weight loss, preserving the structure of intestinal tissues, and ameliorating the dysregulation of inflammatory cytokines (TNF-α, IL-6, and IL-10). Meanwhile, IOP-0 protected the colonic mucosal barrier by promoting the tight junction protein ZO-1 and occludin expression. In addition, IOP-0 was able to maintain intestinal homeostasis and improve intestinal function by regulating the gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs). These results suggest that IOP-0 might be a potential dietary supplement for the prevention and treatment of ulcerative colitis.

[Wideband acoustic immittance characteristics and machine learning-based diagnostic model for children with large vestibular aqueduct syndrome].

Objective:This study was to investigate the wideband acoustic immittance（WAI） characteristics of children with large vestibular aqueduct syndrome（LVAS） and to construct a diagnostic model for LVAS based on WAI and machine learning（ML） techniques. Methods:We performed a retrospective analysis of the data from 38 children（76 ears） with LVAS and 44 children（88 ears） with normal hearing. The data included conventional audiological examination, temporal bone CT scan and WAI test. We performed statistical analysis and developed multivariate diagnostic models based on different ML techniques. Results:The two groups were balanced in terms of ear, gender, and age（P>0.05）. The wideband absorbance（WBA） of the LVAS group was significantly lower than that of the control group at 1 000-2 519 Hz, while the WBA of the LVAS group was significantly higher than that of the control group at 4 000-6 349 Hz（P<0.05）. WBA at 5 039 Hz under ambient pressure had a certain diagnostic value（AUC=0.767）. The multivariate diagnostic model had a high diagnostic value（AUC>0.8）, among which the KNN model performed the best（AUC=0.961）. Conclusion:The WAI characteristics of children with LVAS are significantly different from those of normal children. The diagnostic model based on WAI and ML techniques has high accuracy and reliability, and provides new ideas and methods for intelligent diagnosis of LVAS.

[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

Microarray analysis of tRNA-derived small RNA (tsRNA) in LPS-challenged macrophages treated with metformin.

Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions.

A physically constrained Monte Carlo-Neural Network coupling algorithm for BNCT dose calculation.

BACKGROUND: In boron neutron capture therapy (BNCT)-a form of binary radiotherapy-the primary challenge in treatment planning systems for dose calculations arises from the time-consuming nature of the Monte Carlo (MC) method. Recent progress, including the use of neural networks (NN), has been made to accelerate BNCT dose calculations. However, this approach may result in significant dose errors in both the tumor and the skin, with the latter being a critical organ in BNCT. Furthermore, owing to the lack of physical processes in purely NN-based approaches, their reliability for clinical dose calculations in BNCT is questionable. PURPOSE: In this study, a physically constrained MC-NN (PCMC-NN) coupling algorithm is proposed to achieve fast and accurate computation of the BNCT three-dimensional (3D) therapeutic dose distribution. This approach synergizes the high precision of the MC method with the speed of the NN and utilizes physical conservation laws to constrain the coupling process. It addresses the time-consuming issue of the traditional MC method while reducing dose errors. METHODS: Clinical data were collected from 113 glioblastoma patients. For each patient, the 3D dose distributions for both the coarse and detailed dose grids were calculated using the MC code PHITS. Among these patients, the data from 14 patients were allocated to the test set, 9 to the validation set, and the remaining to the training set. A neural network, 3D-Unet, was built based on the coarse grid dose and patient CT information to enable fast and accurate computation of the 3D detailed grid dose distribution of BNCT. RESULTS: Statistical evaluations, including relative deviation, dose deviation, mean absolute error (MAE), and mean absolute percentage error (MAPE) were conducted. Our findings suggested that the PCMC-NN algorithm substantially outperformed the traditional NN and interpolation methods. Furthermore, the proposed algorithm significantly reduced errors, particularly in the skin and GTV, and improved computational accuracy (hereinafter referred to simply as 'accuracy') with a MAPE range of 1.6%-4.0% and a maximum MAE of 0.3 Gy (IsoE) for different organs. The dose-volume histograms generated by the PCMC-NN aligned well with those obtained from the MC method, further validating its accuracy. CONCLUSIONS: The PCMC-NN algorithm enhanced the speed and accuracy of BNCT dose calculations by combining the MC method with the NN algorithm. This indicates the significant potential of the proposed algorithm for clinical applications in optimizing treatment planning.

Facile Preparation of Magnetic COF-on-COF for Rapid Adsorption and Determination of Sulforaphane from Cruciferous Vegetables.

Sulforaphane (SFN) is a natural isothiocyanate compound widely abundant in cruciferous vegetables with multiple bioactive functions. However, traditional analytical methods for the extraction and determination of SFN are cumbersome, time-consuming, and low sensitivity with large amounts of organic solvents. Herein, novel magnetic COF-on-COFs (MB-COFs) were fabricated using Fe3O4 as a magnetic core and COFs-1 grown with COFs-2 as a shell, and they were used as efficient adsorbents of magnetic dispersive solid-phase extraction for rapid quantification of SFN in cruciferous vegetables by combining with HPLC-MS/MS. At the optimal ratio of COFs-1 to COFs-2, MB-COFs had a spherical cluster-like structure and a rough surface, with a sufficient magnetic response for rapid magnetic separation (1 min). Due to the introduction of Fe3O4 and COFs-2, MB-COFs exhibited outstanding extraction efficiencies for SFN (92.5-97.3%), which was about 18-72% higher than that of the bare COFs. Moreover, MB-COFs showed good adsorption capacity (Qm of 18.0 mg/g), rapid adsorption (5 min) and desorption (30 s) to SFN, and favorable reusability (≥7 cycles) by virtue of their unique hierarchical porous structure. The adsorption kinetic data were well fitted by the pseudo-second-order, Ritchie-second-order, intra-particle diffusion, and Elovich models, while the adsorption isotherm data were highly consistent with the Langmuir, Temkin, and Redlich-Peterson models. Finally, under the optimized conditions, the developed method showed a wide linear range (0.001-0.5 mg/L), high sensitivity (limits of quantification of 0.18-0.31 µg/L), satisfactory recoveries (82.2-96.2%) and precisions (1.8-7.9%), and a negligible matrix effect (0.82-0.97). Compared to previous methods, the proposed method is faster and more sensitive and significantly reduces the use of organic solvents, which can achieve the efficient detection of large-scale samples in practical scenarios. This work reveals the high practical potential of MB-COFs as adsorbents for efficient extraction and sensitive analysis of SFN in cruciferous vegetables.

Enhancing precision in lung tumor ablation through innovations in CT-guided technique and angle control.

BACKGROUND: This retrospective study aimed to evaluate the precision and safety outcomes of image-guided lung percutaneous thermal ablation (LPTA) methods, focusing on radiofrequency ablation (RFA) and microwave ablation (MWA). The study utilized an innovative angle reference guide to facilitate these techniques in the treatment of lung tumors. METHODS: This study included individuals undergoing LPTA with the assistance of laser angle guide assembly (LAGA) at our hospital between April 2011 and March 2021. We analyzed patient demographics, tumor characteristics, procedure details, and complications. Logistic regressions were employed to assess risk factors associated with complications. RESULTS: A total of 202 patients underwent ablation for 375 lung tumors across 275 sessions involving 495 ablations. Most procedures used RFA, especially in the right upper lobe, and the majority of ablations were performed in the prone position (49.7%). Target lesions were at a median depth of 39.3 mm from the pleura surface, and remarkably, 91.9% required only a single puncture. Complications occurred in 31.0% of ablations, with pneumothorax being the most prevalent (18.3%), followed by pain (12.5%), sweating (6.5%), fever (5.0%), cough (4.8%), hemothorax (1.6%), hemoptysis (1.2%), pleural effusion (2.0%), skin burn (0.6%), and air emboli (0.2%). The median procedure time was 21 min. Notably, smoking/chronic obstructive pulmonary disease emerged as a significant risk factor for complications. CONCLUSION: The LAGA-assisted LPTA enhanced safety by improving accuracy and reducing risks. Overall, this investigation contributes to the ongoing efforts to refine and improve the clinical application of these thermal ablation techniques in the treatment of lung tumors.

Associations of glycosylated hemoglobin, pre-diabetes, and type 2 diabetes with incident lung cancer: A large prospective cohort study.

BACKGROUND: The association of pre-diabetes and type 2 diabetes (T2D) with incident lung cancer is uncertain, and the incident risk across the glycemic spectrum is unclear. We aimed to explore the associations of glycosylated hemoglobin (HbA1c), pre-diabetes, and T2D with incident lung cancer in a large prospective cohort. METHODS: Leveraging a total of 210,779 cancer-free adults recruited in the UK Biobank between 2006 and 2010. We performed multivariable Cox proportional hazards models and restricted cubic spline methods to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of HbA1c, pre-diabetes, and T2D with incident lung cancer. RESULTS: During a median follow-up of 11.06 years, 1738 incident lung cancer cases were ascertained. The incidence of lung cancer was 20% higher among people with diabetes (HR: 1.20, 95% CI: 1.02 to 1.42) and 38% higher among people with pre-diabetes (HR: 1.38, 95% CI: 1.15 to 1.65). After dividing people with diabetes by whether taking antidiabetic medications, the incidence was 28% higher among people with diabetes without medications (HR: 1.28, 95% CI: 1.02 to 1.61) and 15% higher among people with diabetes with medications (HR: 1.15, 95% CI: 0.93 to 1.41). The increased risk of incident lung cancer for each standard deviation (6.45 mmol/mol) increase in HbA1c was more pronounced across HbA1c values of 32-42 mmol/mol (HR: 1.37, 95% CI: 1.18 to 1.59). The risk was more pronounced among participants <60 years. CONCLUSIONS: Pre-diabetes and T2D are associated with an increased incidence of lung cancer. The increased risk of incident lung cancer is more pronounced across HbA1c values of 32-42 mmol/mol, which are currently considered normal values.

Effect of Huaier granule on prognosis of breast cancer: A single-center propensity score matching retrospective study.

BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION: In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.

Breast-conserving surgery is associated with a lower incidence of suicide among females with breast cancer in the United States: a population-based retrospective cohort study.

BACKGROUND: With comparable overall survival and local recurrence rates with mastectomy, breast-conserving surgery (BCS) has become the cornerstone of therapy for breast cancer; however, the difference in the incidence of suicide between BCS and mastectomy among breast cancer survivors remains unclear. This study evaluated the mortality risk from suicide among breast cancer survivors and compared suicide risk between BCS and mastectomy using a population-based cohort. MATERIALS AND METHODS: Female patients newly diagnosed with first primary breast cancer, recorded in the Surveillance, Epidemiology and End Results database, were included. Standardized mortality ratio (SMR) and cumulative mortality rate from suicide among those who underwent BCS and mastectomy were compared. RESULTS: A total of 1 190 991 patients with newly diagnosed first primary breast cancer were included in the study, of whom 56.5% underwent BCS and 36.1% underwent mastectomy. During the follow-up period, 667 suicides were recorded. Patients who underwent mastectomy exhibited significantly higher suicide mortality than the general population [mortality rate, 8.16 per 100 000 person-years; SMR 1.18 (95% CI 1.05-1.33)], while there was no significant difference in suicide rate between patients who underwent BCS and the general population [SMR 0.92 (95% CI 0.83-1.02)]. Multivariate Cox analysis revealed that BCS, compared with mastectomy, was associated with a significantly decreased risk of suicide among females with breast cancer [hazard ratio 0.80 (95% CI 0.68-0.95); P = 0.009]. CONCLUSION: BCS was associated with a significantly lower incidence of suicide among females with breast cancer. BCS offers a compelling option for improving the quality of life and self-esteem of patients with cancer and provides a novel perspective on cancer management.

Increasing and high prevalence of moderate to severe obstructive sleep apnea in acute ischemic stroke in Taiwan.

STUDY OBJECTIVES: The prevalence of obstructive sleep apnea (OSA) after stroke is variable, likely due to the time of examination and patient population. Although risk factors for OSA are well established, those for OSA in patients with ischemic stroke have not yet been fully identified. Therefore, we examined the prevalence of OSA and identified risk factors for OSA in the acute stage of ischemic stroke in the Taiwanese population. METHODS: A total of 103 patients with acute ischemic stroke were screened for OSA by performing polysomnography. The demographic and clinical data, Epworth Sleepiness Scale score, and other stroke risk factors were recorded. Sleep parameters, namely sleep efficiency, sleep stages, apnea-hypopnea index, and oxygen desaturation index were recorded. Logistic regression analysis was conducted to determine clinical and demographic risk factors for moderate to severe OSA in patients with stroke. RESULTS: We determined that 91.2% of the patients had OSA in the acute stage of ischemic stroke, and 70% of the patients had moderate to severe OSA. Multivariate logistic regression analysis revealed that patients aged ≥65 years had a significantly higher risk of moderate to severe OSA (adjusted OR: 3.04, 95% CI: 1.20-7.69, p < 0.05) compared with patients with ischemic stroke aged <50 years. CONCLUSION: OSA is highly prevalent among patients with ischemic stroke in the acute stage, and those aged ≥65 years had a significantly increased risk of moderate to severe OSA. In clinical practice, routine PSG screening of OSA may be necessary among older patients with stroke.

Isoquercitrin alleviates lipopolysaccharide-induced intestinal mucosal barrier damage in mice by regulating TLR4/MyD88/NF-κB signaling pathway and intestinal flora.

Intestinal mucosal barrier damage is closely associated with the development of several intestinal inflammatory diseases. Isoquercitrin (IQ) is a natural flavonoid compound derived from plants, which exhibits high antioxidant and anti-inflammatory activity with minimal side effects in humans. Therefore, it shows great potential for preventing and treating intestinal mucosal barrier damage. This study aims to investigate the ameliorative effect and mechanism of IQ on lipopolysaccharide (LPS)-induced intestinal mucosal barrier damage in mice. The mice were treated with IQ for 7 days and then injected with LPS to induce intestinal mucosal barrier damage. The results revealed that IQ treatment alleviated LPS-induced intestinal mucosal barrier damage in mice, which can be evidenced by the improvements in intestinal morphology and the promotion of expression in intestinal tight junctions (ZO-1, Claudin-1, and Occludin), as well as MUC2 mucin. IQ also attenuated intestinal inflammatory responses by inhibiting the TLR4/MyD88/NF-κB signaling pathway and reducing the expression and plasma levels of IL-6, IL-1ß, and TNF-α. Furthermore, IQ significantly increased the relative abundance of beneficial bacteria, including Dubosiella, Akkermansia muciniphila and Faecalibaculum rodentium, while suppressing the growth of harmful bacteria such as Mucispirillum schaedleri in the intestinal flora of mice. Consequently, IQ can alleviate the LPS-induced intestinal mucosal barrier damage in mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway and modulating the intestinal flora.

Bio-Inspired Microreactors Continuously Synthesize Glucose Precursor from CO2 with an Energy Conversion Efficiency 3.3 Times of Rice.

Excessive CO2 and food shortage are two grand challenges of human society. Directly converting CO2 into food materials can simultaneously alleviate both, like what green crops do in nature. Nevertheless, natural photosynthesis has a limited energy efficiency due to low activity and specificity of key enzyme D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). To enhance the efficiency, many prior studies focused on engineering the enzymes, but this study chooses to learn from the nature to design more efficient reactors. This work is original in mimicking the stacked structure of thylakoids in chloroplasts to immobilize RuBisCO in a microreactor using the layer-by-layer strategy, obtaining the continuous conversion of CO2 into glucose precursor at 1.9 nmol min-1 with enhanced activity (1.5 times), stability (≈8 times), and reusability (96% after 10 reuses) relative to the free RuBisCO. The microreactors are further scaled out from one to six in parallel and achieve the production at 15.8 nmol min-1 with an energy conversion efficiency of 3.3 times of rice, showing better performance of this artificial synthesis than NPS in terms of energy conversion efficiency. The exploration of the potential of mass production would benefit both food supply and carbon neutralization.