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A key goal of modern medicine is target-specific therapeutic intervention. However, most drugs lack selectivity, resulting in 'off-target' side effects. To address the requirements of 'targeted therapy,' aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates ( ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor β-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC. [ABSTRACT FROM AUTHOR]

To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019-1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052-3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320-2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046-1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273-1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Currently, immunotherapy is being widely used for treating cancers. However, the significant heterogeneity in patient responses is a major challenge for its successful application. CD8-positive T cells (CD8 + T cells) play a critical role in immunotherapy. Both their infiltration and functional status in tumors contribute to treatment outcomes. Therefore, accurate monitoring of CD8 + T cells, a potential biomarker, may improve therapeutic strategy. Positron emission tomography (PET) is an optimal option which can provide molecular imaging with enhanced specificity. This review summarizes the mechanism of action of CD8 + T cells in immunotherapy, and highlights the recent advancements in PET-based tracers that can visualize CD8 + T cells and discusses their clinical applications to elucidate their potential role in cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Du, Wang, Cui, Wang, Zhao, Li and Li.)

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of the heart and is considered to be the leading cause of morbidity and death in patients with diabetes. Currently, there is no specific treatment or preventive drug for DCM, and there is an urgent need to develop new drugs to treat DCM. Traditional Chinese medicine (TCM) has rich experience in the treatment of DCM, and its characteristics of multi-target, multi-pathway, multi-component, and few side effects can effectively deal with the complexity and long-term nature of DCM. Growing evidence suggests that myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, and advanced glycation end product deposition were the main pathologic mechanisms of DCM. According to the pathological mechanism of DCM, this study revealed the potential of metabolites and prescriptions in TCM against DCM from the perspective of signaling pathways. The results showed that TGF-β/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, and Wnt/β-catenin signaling pathways were the key signaling pathways for TCM treatment of DCM. The aim of this study was to summarize and update the signaling pathways for TCM treatment of DCM, to screen potential targets for drug candidates against DCM, and to provide new ideas and more experimental evidence for the clinical use of TCM treatment of DCM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liu, Liu, Xing, Liu, Wu, Hu and Zhang.)

Context: Helicobacter pylori ( H. pylori ), a spiral-shaped bacterium, is closely associated with chronic, progressive gastric mucosal damage, gastric atrophy, and even gastric cancer (GC). An increasing number of studies have addressed the correlation between long noncoding RNAs (lncRNAs) and H. pylori pathogenicity in GC., Objective: In this study, we found that the expression level of LINC00659 gradually increased in the progression from atrophic gastritis, intestinal metaplasia, and dysplasia to GC in H. pylori -infected patients. Thus, we aimed to further explore the function of LINC00659 in the progression of gastritis to cancer under H. pylori infection., Materials and Methods: StarBase predictions, ribonucleic acid (RNA)-binding protein immunoprecipitation assays, and gene ontology functional annotation (GO)/Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to identify the RNA-binding proteins of LINC00659; moreover, qRT‒PCR, western blotting, RNA interference, and immunofluorescence assays were used to investigate the function of LINC00659., Results: LINC00659 bound directly to the RNA-binding protein polypyrimidine tract-binding protein (PTBP1). Importantly, qRT‒PCR and western blot assays demonstrated that PTBP1 expression increased in the progression from inflammation to cancer in the stomach of H. pylori -infected patients and H. pylori -infected GES-1 cells. However, LINC00659 knockdown downregulated PTBP1 expression and inhibited PTBP1 binding under H. pylori infection. Finally, LINC00659 knockdown significantly reduced H. pylori -induced human gastric epithelial cell senescence and suppressed interleukin (IL)-6 and IL-8 secretion by reducing the phosphorylation level of NF-κB p65., Conclusions: This study indicated that LINC00659 may have the potential to be a novel promising prognostic and therapeutic marker for H. pylori -associated gastric diseases., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Objective: This research aimed to elucidate the relationship between testosterone levels and serum soluble klotho (S-klotho) concentrations in females aged 40-79 years using the National Health and Nutrition Examination Survey (NHANES) dataset., Design: Associations between testosterone and S-klotho were assessed through multivariable linear regression methodologies, spanning nonadjusted, minimally adjusted, and fully adjusted models., Settings: The investigation was conducted as a cross-sectional analysis utilizing the NHANES database., Participants: From 20,146 NHANES participants between 2013 and 2016, 2,444 females met the stipulated inclusion and exclusion criteria., Results: Free androgen index (FAI) showcased a negative correlation with S-klotho levels across all regression models (nonadjusted: β -7.08, 95% CI -13.39- -0.76; minimally adjusted: β -9.73, 95% CI -16.6- -2.84; fully adjusted: β -7.63, 95% CI -14.75-0.51). Conversely, total testosterone did not exhibit significant associations with S-klotho across the models. In the nonadjusted model, estradiol was positively associated with S-klotho concentrations (β 0.14, 95% CI 0.05-0.23), but this significance was not retained in subsequent regression models., Conclusion: Findings suggest that in U.S. females aged 40-79 years, FAI negatively correlates with S-klotho concentrations, while there is the lack of significant associations for total testosterone and estradiol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Zhang, Hao, Du, Ao, Zhu and Huang.)

Background: Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer., Objective: The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice., Methods: Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days., Results: Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment., Conclusion: The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth., Methods: This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes., Results: Of the 3,100,122 women, preterm birth occurred in 9.45% (292,857) population, with post-term birth accounting for 4.54% (140,851). The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001], and higher GWG z-scores (quantile 3: OR: 1.42, 95% CI: 1.41 to 1.44, P < 0.001; quantile 4: OR: 2.79, 95% CI: 2.76 to 2.82, P < 0.001) were positively associated with preterm birth. Low GWG z-score (OR: 1.18, 95% CI: 1.16 to 1.19, P < 0.001) was positively associated with an increased risk of post-term birth. However, higher GWG z-scores (quantile 3: OR: 0.84, 95% CI: 0.83 to 0.85, P < 0.001; quantile 4: 0.59, 95% CI: 0.58 to 0.60, P < 0.001) was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women (OR: 0.96, 95% CI: 0.94 to 0.98, P < 0.001)., Conclusion: Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth., (© 2023. The Author(s).)

Background: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology., Results: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis., Conclusion: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF., (© 2023. The Author(s).)

Background: Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women's perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy., Methods: We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro., Results: Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women's attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate., Conclusions: Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.

By 2040, ~100 million people will have glaucoma. To date, there are a lack of high-efficiency glaucoma diagnostic tools based on visual fields (VFs). Herein, we develop and evaluate the performance of 'iGlaucoma', a smartphone application-based deep learning system (DLS) in detecting glaucomatous VF changes. A total of 1,614,808 data points of 10,784 VFs (5542 patients) from seven centers in China were included in this study, divided over two phases. In Phase I, 1,581,060 data points from 10,135 VFs of 5105 patients were included to train (8424 VFs), validate (598 VFs) and test (3 independent test sets-200, 406, 507 samples) the diagnostic performance of the DLS. In Phase II, using the same DLS, iGlaucoma cloud-based application further tested on 33,748 data points from 649 VFs of 437 patients from three glaucoma clinics. With reference to three experienced expert glaucomatologists, the diagnostic performance (area under curve [AUC], sensitivity and specificity) of the DLS and six ophthalmologists were evaluated in detecting glaucoma. In Phase I, the DLS outperformed all six ophthalmologists in the three test sets (AUC of 0.834-0.877, with a sensitivity of 0.831-0.922 and a specificity of 0.676-0.709). In Phase II, iGlaucoma had 0.99 accuracy in recognizing different patterns in pattern deviation probability plots region, with corresponding AUC, sensitivity and specificity of 0.966 (0.953-0.979), 0.954 (0.930-0.977), and 0.873 (0.838-0.908), respectively. The 'iGlaucoma' is a clinically effective glaucoma diagnostic tool to detect glaucoma from humphrey VFs, although the target population will need to be carefully identified with glaucoma expertise input., Competing Interests: Competing interestsD.T. is the co-inventor of a few patents for deep learning systems on eye diseases. X.Z. and Y.Q. are the co-inventors of patents for deep learning system on glaucoma diagnosis. The other authors declare no competing interests., (© The Author(s) 2020.)

Ethnopharmacological Relevance: Diabetic retinopathy (DR) is a terrible microvascular disorder causing blindness. Retinal inflammation is the early stage in DR, which is believed to play a crucial role in the development of it. Shengpuhuang-tang (ST), a traditional herbal formula, which has effective treatment of fundus bleeding disorder. ST exerts protective effects against DR in rats, but its underlying mechanism of this efficacy remains unknown. Thus, the objective of this study is to examine the mechanism and the efficacy of ST on retinal inflammation in streptozotocin-induced diabetic rats., Materials and Methods: The administration of ST was initiated at 4 weeks after diabetes induction and continued for 12 weeks. Retinal vessel permeability was evaluated by using FITC-dextran and Evans blue. Retinal leukostasis was evaluated with FITC-coupled concanavalin A lectin (ConA). Moreover, western blotting was performed to detect TNF-α, ICAM-1 and the relative expression levels of IκBα, IKKβ, and p65 in vivo., Results: The results showed that the retinal inflammation in streptozotocin-induced diabetic rats was significantly decreased by ST. ST could decreased the expression levels of TNF-α, ICAM-1 and inhibited the expression of p-IKKβ, p-p65 and IκBα. It could also inhibited the nuclear transfer of p65., Conclusions: In conclusion, these data suggested that ST may have potential treatment strategies against early stage of diabetic retinopathy through NF-κB pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to explore the status of prevention and nursing on venous thromboembolism (VTE) among perioperative patients with lung cancer in Chinese hospital., Methods: A self-designed questionnaire was used to investigate 108 head nurses from tertiary hospitals during the first West China Forum on Chest Enhanced Recovery After Surgery (ERAS)., Results: (1) Current status of assessment tools and prevention guidelines: 97.22% of the hospitals have carried out VTE risk assessments for surgical patients with lung cancer, 67.59% of the hospitals have established the nursing prevention specifications of VTE. (2) Current status of screening, precaution and follow-up: 56.48% of the hospitals have taken different approach to screen VTE for lung cancer patients in pre-operative period. 90.74% of the hospitals and 52.78% of the hospitals had VTE prophylaxis for hospitalized and discharged patients, but only 17.59% of hospitals were followed up on the incidence of VTE for discharged patients. (3) There was no statistically significant difference in VTE prevention between different type hospitals (P>0.05). But, all patients in the specialist hospital have been fully implemented on VTE risk assessment and VTE prevention (100.00%)., Conclusions: The clinical staff have already realized the importance of VTE prevention, and the VTE prevention in perioperative patients with lung cancer has received extensive attention. But there is still lack of effective risk assessment tools and standardized guidelines of VTE prevention.

A key goal of modern medicine is target-specific therapeutic intervention. However, most drugs lack selectivity, resulting in 'off-target' side effects. To address the requirements of 'targeted therapy,' aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates (ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438 For further resources related to this article, please visit the WIREs website., (© 2016 Wiley Periodicals, Inc.)