Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

Global Research Trends in Adipose Stem Cell Tissue Engineering: A Scientometric Research.

Adipose Stem Cell Tissue Engineering (ASCTE) has emerged as a promising field of research in recent years. To gain comprehensive insights into this field, we conducted a comprehensive bibliometric analysis using Web of Science Core Collection and various bibliometric tools, including CiteSpace, VOS viewer, and R-Bibliometrix. Our analysis focuses on the historical development and evolution of active topics in ASCTE from a time-dynamics perspective, covering 4522 publications, 3924 academic institutions, and 873 journals, with significant growth observed over the past two decades. In terms of the global research landscape, the United States and China dominate the field. Shanghai Jiao Tong University, the University of Pittsburgh, and Ming Ho University are the top three institutions contributing to research in this area. Biomaterials is identified as the central journal in terms of cocitation analysis. Our analysis also reveals new areas of development, such as 3D printing, platelet lysate, and clinical practice, as well as current trends in hydrogels, nanomaterials, and extracellular vesicles. These findings point to exciting prospects for future ASCTE research. Unlike previous subjective reviews, our bibliometric analysis provides an objective assessment of the current state and emerging trends in ASCTE research, allowing researchers to identify popular research areas and explore new directions in this dynamic field.

Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol.

BACKGROUND: The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. METHODS: To address these gaps in knowledge, we conducted a comprehensive analysis of microarray and RNA-seq datasets to elucidate shared biomarkers and biological pathways involved in the pathogenesis of kidney stones and diabetes. An assortment of bioinformatic approaches was employed to illuminate the common molecular markers and associated pathways, thereby contributing to the identification of innovative therapeutic targets. Further investigation into the molecular mechanisms of resveratrol in preventing these conditions was conducted using molecular docking simulation and first-principles calculations. RESULTS: The study identified 11 potential target genes associated with kidney stones and diabetes through the intersection of genes from weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. Among these, Interleukin 11 (IL11) emerged as a pivotal hub gene and a potential diagnostic biomarker for both conditions, particularly in males. Expression analysis of IL11 demonstrated elevated levels in kidney stones and diabetes groups compared to controls. Additionally, IL11 exhibited correlations with specific cell types and differential expression in normal and pathological conditions. Gene set enrichment analysis (GSEA) highlighted significant disparities in biological processes, pathways, and immune signatures associated with IL11. Moreover, molecular docking simulation of resveratrol towards IL11 and a first-principles investigation of Ca adsorption on the resveratrol surface provided structural evidence for the development of resveratrol-based drugs for these conditions. CONCLUSIONS: Overall, this investigation illuminates the discovery of common molecular mechanisms underlying kidney stones and diabetes, unveils potential diagnostic biomarkers, and elucidates the significance of IL11 in these conditions. It also provides insights into IL11 as a promising therapeutic target and highlights the role of resveratrol. Nonetheless, further research is warranted to enhance our understanding of IL11 targeting mechanisms and address any limitations in the study.

[Effect of BBM gene on callus growth and ginsenoside content in Panax quinquefolius].

Baby Boom(BBM) gene is a key regulatory factor in embryonic development and regeneration, cell proliferation, callus growth, and differentiation promotion. Since the genetic transformation system of Panax quinquefolius is unstable with low efficiency and long period, this study attempted to transfer BBM gene of Zea mays to P. quinquefolius callus by gene gunship to investigate its effect on the callus growth and ginsenoside content, laying a foundation for establishing efficient genetic transformation system of P. quinquefolius. Four transgenic callus of P. quinquefolius with different transformation events were obtained by screening for glufosinate ammonium resistance and molecular identification by PCR. The growth state and growth rate of wild-type and transgenic callus were compared in the same growth period. The content of ginsenoside in transgenic callus was determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The results showed that transgenic callus growth rate was significantly higher than that of wild-type callus. In addition, the content of ginsenoside Rb_1, Rg_1, Ro, and Re was significantly higher than that in wild-type callus. The paper preliminarily proved the function of BBM gene in promoting growth rate and increasing ginsenoside content, which provided a scientific basis to establish a stable and efficient genetic transformation system for Panax plants in the future.

ZmnMAT1, a nuclear-encoded type I maturase, is required for the splicing of mitochondrial Nad1 intron 1 and Nad4 intron 2.

Maturases can specifically bind to intron-containing pre-RNAs, folding them into catalytic structures that facilitate intron splicing in vivo. Plants possess four nuclear-encoded maturase-related factors (nMAT1-nMAT4) and some maturases have been shown to involve in the splicing of different mitochondrial group II introns; however, the specific biological functions of maturases in maize are largely uncharacterized. In this study, we identified a maize ZmnMAT1 gene, which encodes a mitochondrion-localized type I maturase with an RT domain at N-terminus and an X domain at C-terminus. Loss-of-function mutation in ZmnMAT1 significantly reduced the splicing efficiencies of Nad1 intron 1 and Nad4 intron 2, and showed arrested embryogenesis and endosperm development, which may be related to impaired mitochondrial ultrastructure and function due to the destruction of the assembly and activity of complex I. Direct physical interaction was undetectable between ZmnMAT1 and the proteins associated with the splicing of Nad1 intron 1 and/or Nad4 intron 2 by yeast two-hybrid assays, suggesting the complexity of group II intron splicing in plants.

Development and validation of a novel model for predicting the survival of bladder cancer based on ferroptosis-related genes.

The role of ferroptosis, a new form of cell death, in bladder cancer (BC) has not been sufficiently studied. This study aimed to establish a prognostic prediction model for BC patients based on the expression profile of ferroptosis-related genes (FRG). The expression profiles of BC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A total of 80 differentially expressed genes (DEGs) related to FRG were identified among which 37 DEGs were found to have a prognostic value. Eleven genetic markers including SLC2A12, CDO1, JDP2, MAFG, CAPG, RRM2, SLC2A3, SLC3A2, VDAC2, GCH1, and ANGPTL7 were identified through the LASSO regression analysis. The ROC curve analysis showed that the AUC was 0.702, 0.664, and 0.655 for the 1-year, 3-year, and 5-year survival outcomes, respectively. The prediction performance was verified in the TCGA-testing set and external set GSE13507. Multivariate Cox proportional hazards analysis showed that the risk score was an independent prognostic predictor. Moreover, we found differences in gene mutation, gene expression, and immune cell infiltration between the high and low-risk groups of BC patients. Finally, a nomogram was constructed by integrating clinical features and FRG signatures to predict the survival outcomes of BC patients. In addition, the differential expression of FRG mRNA and protein was verified through PCR and HPA online site. The characteristics of 11 FRG genes were examined and a prognostic nomogram for predicting the overall survival of BC was established.

Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking.

Restless legs syndrome (RLS) is a neurological motor disorder with a high prevalence. The treatment efficacy of RLS is unsatisfactory. Radix Paeoniae Alba (RPA) can effectively treat RLS symptoms such as the discomfort of the legs. RPA has great potential for the development of new medications for RLS. Hence, we explored the mechanism of RPA in the treatment of RLS using network pharmacology and molecular docking. The active components and targets of RPA were obtained from the Traditional Chinese Medicine System Pharmacology database and analysis platform and PharmMapper platform. The RLS-related targets were found in GeneCards, OMIM, DrugBank, and DisGeNET databases. The overlapping targets of RPA and RLS were then collected. The "active components-overlapping targets" network was built, and network topology analysis was performed. Furthermore, Cytoscape 3.9.1 software was used to screen the key components of RPA in the treatment of RLS. Protein-protein interaction was performed using the Search Tool for the Retrieval of Interacting Genes. The gene ontology functions and Kyoto Encyclopedia of Genes and Genomes signaling pathways were analyzed using ClusterProfiler, PathView, and other R packages to reveal the main mechanism of RPA in treating RLS. Component and protein structures were downloaded from the Traditional Chinese Medicine System Pharmacology and Protein Data Bank databases, respectively. The AutoDock 4.2.6 software was used for molecular docking. A total of 12 active components and 109 targets of RPA, as well as 2387 RLS-related targets, were collected. Following that, 47 overlapping targets were obtained. Furthermore, 5 key components and 12 core targets were screened. The results of gene ontology functions were as follows: 2368 biological processes, 264 molecular functions, and 164 cellular components. A total of 207 Kyoto Encyclopedia of Genes and Genomes signaling pathways were obtained, including the lipid and atherosclerosis pathway, the endocrine resistance pathway, the prolactin signaling pathway, and the IL-17 signaling pathway. The components and the core targets completed molecular docking stably. RPA has multi-component, multi-target, and multi-pathway characteristics in treating RLS, which could provide a basis for future research and improve clinical efficacy.

Immunohistochemistry scoring of breast tumor tissue microarrays: A comparison study across three software applications.

Digital pathology can efficiently assess immunohistochemistry (IHC) data on tissue microarrays (TMAs). Yet, it remains important to evaluate the comparability of the data acquired by different software applications and validate it against pathologist manual interpretation. In this study, we compared the IHC quantification of 5 clinical breast cancer biomarkers-estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6)-across 3 software applications (Definiens Tissue Studio, inForm, and QuPath) and benchmarked the results to pathologist manual scores. IHC expression for each marker was evaluated across 4 TMAs consisting of 935 breast tumor tissue cores from 367 women within the Nurses' Health Studies; each women contributing three 0.6-mm cores. The correlation and agreement between manual and software-derived results were primarily assessed using Spearman's ρ, percentage agreement, and area under the curve (AUC). At the TMA core-level, the correlations between manual and software-derived scores were the highest for HER2 (ρ ranging from 0.75 to 0.79), followed by ER (0.69-0.71), PR (0.67-0.72), CK5/6 (0.43-0.47), and EGFR (0.38-0.45). At the case-level, there were good correlations between manual and software-derived scores for all 5 markers (ρ ranging from 0.43 to 0.82), where QuPath had the highest correlations. Software-derived scores were highly comparable to each other (ρ ranging from 0.80 to 0.99). The average percentage agreements between manual and software-derived scores were excellent for ER (90.8%-94.5%) and PR (78.2%-85.2%), moderate for HER2 (65.4%-77.0%), highly variable for EGFR (48.2%-82.8%), and poor for CK5/6 (22.4%-45.0%). All AUCs across markers and software applications were ≥0.83. The 3 software applications were highly comparable to each other and to manual scores in quantifying these 5 markers. QuPath consistently produced the best performance, indicating this open-source software is an excellent alternative for future use.

Omega-3 Polyunsaturated Fatty Acids, Gut Microbiota, Microbial Metabolites, and Risk of Colorectal Adenomas.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are thought to protect against colorectal adenoma (CRA) development. We aimed to further understand the underlying mechanisms by examining the relationships between ω-3 PUFAs and the gut microbiota on CRAs. We assessed the mucosal microbiota via bacterial 16S rRNA sequencing among 217 CRA cases and 218 controls who completed PUFA intake questionnaires. The overall microbial composition was assessed by α-diversity measurements (diversity, richness, and evenness). Global metabolomics was conducted using a random subset of case−control pairs (n = 50). We compared microbiota and metabolite signatures between cases and controls according to fold change (FC). Odds ratios (OR) and confidence intervals (CI) were estimated from logistic regression for associations of ω-3 PUFAs and the microbiota with CRAs. We observed an inverse association between overall ω-3 PUFA intake and CRAs, especially for short-chain ω -3 PUFAs (OR = 0.45, 95% CI: 0.21, 0.97). Such inverse associations were modified by bacterial evenness (p-interaction = 0.03). Participants with higher levels (FC > 2) of bile acid-relevant metabolites were more likely to have CRAs than the controls, and the correlation between bile acids and bacterial diversity differed by case−control status. Our findings suggest that ω-3 PUFAs are inversely associated with CRA development, and the association may be modified by gut microbiota profiles.

Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses' Health Studies.

BACKGROUND: The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiologic cohorts. METHODS: We followed women with invasive breast cancer from the Nurses' Health Studies with available data on tumor PTEN expression (n = 4,111) and PIK3CA mutation (n = 2,930). PTEN expression was evaluated by IHC and digitally scored (0%-100%). Pyrosequencing of six hotspot mutations of PIK3CA was performed. RESULTS: We found loss of PTEN expression (≤10%) occurred in 17% of cases, and PIK3CA mutations were detected in 11% of cases. After adjusting for clinical and lifestyle factors, PTEN loss was not associated with worse breast cancer-specific mortality among all samples [HR, 0.85; 95% confidence intervals (CI), 0.71-1.03] or among estrogen receptor (ER)-positive tumors (HR, 0.99; 95% CI, 0.79-1.24). However, among ER-negative tumors, PTEN loss was associated with lower breast cancer-specific mortality (HR, 0.68; 95% CI, 0.48-0.95). PIK3CA mutation was not strongly associated with breast cancer-specific mortality (HR, 0.89; 95% CI, 0.67-1.17). Compared with tumors without PTEN loss and without PIK3CA mutation, those with alterations (n = 540) were not at higher risk (HR, 1.07; 95% CI, 0.86-1.34). However, women with both PTEN loss and PIK3CA mutation (n = 38) were at an increased risk of breast cancer-specific mortality (HR, 1.65; 95% CI, 0.83-3.26). CONCLUSIONS: In this large epidemiologic study, the PTEN-mortality association was more pronounced for ER-negative tumors, and the joint PTEN loss and PIK3CA mutation may be associated with worse prognosis. IMPACT: Further studies with a larger sample of ER-negative tumors are needed to replicate our findings and elucidate underlying mechanisms.

Efficacy and safety of high-voltage versus standard-voltage pulsed radiofrequency ablation for patients with neuropathic pain: protocol for a systematic review and meta-analysis.

INTRODUCTION: Pulsed radiofrequency (PRF) ablation is commonly used for the treatment of neuropathic pain (NP). However, it is unclear whether increasing the output voltage of PRF can safely improve its efficacy. This study aims to compare the efficacy and safety of high-voltage PRF ablation and standard-voltage PRF ablation for the treatment of patients with NP. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Library, conference proceedings for relevant abstracts, clinical trials registers (ClinicalTrials.gov) and the WHO's International Clinical Trial Registry Platform (from the date of inception until 15 March 2022). Only randomised controlled trials will be included. Two reviewers (YJ and GF) will independently perform study screening and selection, data extraction, risk-of-bias assessment and quality-of-evidence assessment. The primary outcome of this meta-analysis will be the efficiency rate in patients with NP. The secondary outcomes will include numeric rating scale score, visual analogue scale score, time to take effect, rescue drug dosage, quality of life using the health questionnaire (SF-36) and the incidence of adverse events. Meta-analyses will be conducted using standard meta-analysis software (RevMan V.5.3, The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark). ETHICS AND DISSEMINATION: The requirement for ethical approval was waived as our systematic review will be based on the published literature. The results of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022297804.

Role of skeletal muscle satellite cells in the repair of osteoporotic fractures mediated by ß-catenin.

BACKGROUND: Osteoporosis is a metabolic disease, and osteoporotic fracture (OPF) is one of its most serious complications. It is often ignored that the influence of the muscles surrounding the fracture on the healing of OPF. We aimed to clarify the role of skeletal muscle satellite cells (SMSCs) in promoting OPF healing by ß-catenin, to improve our understanding of SMSCs, and let us explore its potential as a therapeutic target. METHODS: Skeletal muscles were obtained from control non-OPF or OPF patients for primary SMSCs culture (n = 3, 33% females, mean age 60 ± 15.52). Expression of SMSCs was measured. In vivo, 3-month-old female C57BL/6 mice underwent OVX surgery. Three months later, the left tibia fracture model was again performed. The control and the treatment group (n = 24, per group, female). The treatment group was treated with an agonist (osthole). Detection of SMSCs in muscles and fracture healing at 7, 14, and 28 three time points (n = 8, 8, 8, female). To further clarify the scientific hypothesis, we innovatively used Pax7-CreERT2/+ ;ß-cateninfx/fx transgenic mice (n = 12, per group, male). Knock out ß-catenin in SMSC to observe the proliferation and osteogenic differentiation of SMSCs, and OPF healing. In vitro primary cells of SMSCs from 3-month-old litter-negative ß-cateninfx/fx transgenic mice. After adenovirus-CRE transfection, the myogenic and osteogenic differentiation of SMSC was observed. RESULTS: We find that human SMSCs reduced proliferation and osteogenic differentiation in patients with OPF (-38.63%, P < 0.05). And through animal experiments, it was found that activation of ß-catenin promoted the proliferation and osteogenic differentiation of SMSC at the fracture site, thereby accelerating the healing of the fracture site (189.47%, P < 0.05). To prove this point of view, in the in vivo Pax7-CreERT2/+ ;ß-cateninfx/fx transgenic mouse experiment, we innovatively found that knocking out ß-catenin in SMSC will cause a decrease in bone mass and bone microstructure, and accompanied by delayed fracture healing (-35.04%, P < 0.001). At the same time, through in vitro SMSC culture experiments, it was found that their myogenic (-66.89%, P < 0.01) and osteogenic differentiation (-16.5%, P < 0.05) ability decreased. CONCLUSIONS: These results provide the first practical evidence for a direct contribution of SMSCs to promote the healing of OPF with important clinical implications as it may help in the treatment of delayed healing and non-union of OPFs, and mobilization of autologous stem cell therapy in orthopaedic applications.

Diabetes Risk Reduction Diet and Survival after Breast Cancer Diagnosis.

Type II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65-0.97; P trend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58-0.76; P trend < 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer-specific mortality (HR = 0.77; 95% CI = 0.62-0.95) and overall mortality (HR = 0.85; 95% CI = 0.74-0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors. SIGNIFICANCE: This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.

Effect of High-Dispersible Graphene on the Strength and Durability of Cement Mortars.

Graphene's outstanding properties make it a potential material for reinforced cementitious composites. However, its shortcomings, such as easy agglomeration and poor dispersion, severely restrict its application in cementitious materials. In this paper, a highly dispersible graphene (TiO2-RGO) with better dispersibility compared with graphene oxide (GO) is obtained through improvement of the graphene preparation method. In this study, both GO and TiO2-RGO can improve the pore size distribution of cement mortars. According to the results of the mercury intrusion porosity (MIP) test, the porosity of cement mortar mixed with GO and TiO2-RGO was reduced by 26% and 40%, respectively, relative to ordinary cement mortar specimens. However, the TiO2-RGO cement mortars showed better pore size distribution and porosity than GO cement mortars. Comparative tests on the strength and durability of ordinary cement mortars, GO cement mortars, and TiO2-RGO cement mortars were conducted, and it was found that with the same amount of TiO2-RGO and GO, the TiO2-RGO cement mortars have nearly twice the strength of GO cement mortars. In addition, it has far higher durability, such as impermeability and chloride ion penetration resistance, than GO cement mortars. These results indicate that TiO2-RGO prepared by titanium dioxide (TiO2) intercalation can better improve the strength and durability performance of cement mortars compared to GO.

Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics.

The delivery of peptides or protein drugs via the oral route has always presented a significant challenge. Here, nanoparticles for the oral delivery of liraglutide are prepared. The nanoparticles are composed of the biodegradable carrier materials chitosan and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA). In addition, CSKSSDYQC (CSK) and hemagglutinin-2 (HA2) are introduced into the particles to improve the in vivo bioavailability of liraglutide. The size of the nanoparticles is less than 200 nm, and the encapsulation efficiency is approximately 80%. Compared with the subcutaneously injected liraglutide solution group (100%), the relative bioavailability of the nanoparticle group modified with CSK and HA2 reached 10.12%, which is 2.53 times that of the oral liraglutide solution group. In vivo imaging results showed that pHPMA/HA2-CSK chitosan nanoparticles (pHPMA/HA-CCNPs) are retained in the gastrointestinal tract for up to 12 h, which is beneficial for oral absorption. CSK and HA2 modified pHPMA/chitosan nanoparticles significantly improved liraglutide oral bioavailability and therefore have the potential to be applied for oral administration of peptides and proteins.

Synchronous multiple primary lung cancers with shared EGFR mutation but differential imaging findings and pathological subtypes: A case report.

Lung cancer is a leading cause of cancer mortality worldwide. As the incidence of lung cancer increases in recent years, the number of patients diagnosed with synchronous multiple primary lung cancers (SMPLC) is also rising. SMPLC diagnosis is often made based on the clinical course, imaging findings, and histologic and molecular features. Standard lobectomy is the main therapeutic modality for SMPLC. Because maximum retention of lung function is essential, sublobectomy is also a commonly used surgical strategy when appropriate. The question is how to optimize the sequence of lobectomy and sublobectomy for patients with SMPLC. Thoracoscope lobectomy for the primary lesion plus sublobectomy for the secondary lesions is the most commonly used approach. Here we present a case of SMPLC with sublobectomy followed by lobectomy.

Corrigendum: Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF-Tg Mice Model.

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