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Ming-Zhu Chen,1,&ast; Xiao-Lei Chen,2,&ast; Qin Xu,3 Xiao-Dong Cao,2 Meng-Yu Wang,1 Rong Cao1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 2Nursing Department, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 3School of Nursing, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Xu, School of Nursing, Nanjing Medical University, No. 101 of Longmian Road, Jiangning District, Nanijing, 211166, People’s Republic of China, Tel +86 25-86869553, Fax +86 25-86869555, Email qinxu@njmu.edu.cn Xiao-Dong Cao, Email dongdonger99@163.comObjective: To explore the mediating effects of perceived social support between frailty and self-perceived burden (SPB) in elderly patients with diabetes and to provide a theoretical basis for reducing that burden.Methods: A total of 169 elderly patients with diabetes who were hospitalised in the endocrinology department of a third-class hospital in Wuxi between May 2020 and July 2022 were included in this study using the convenience sampling method. Patients were assessed by the general information questionnaire, the Chinese version of the Tilburg frailty inventory (TFI), the Self-Perceived Burden Scale (SPBS) and the Perceived Social Support Scale (PSSS). The SPSS 22.0 software was used for Pearson’s correlation analysis and multiple linear regression analysis. Model four of the SPSS PROCESS was used for mediating the effect analysis.Results: The SPBS of elderly patients with diabetes was positively correlated with the TFI (P < 0.01) and negatively correlated with the PSSS (P < 0.01). The results of the Bootstrap test showed that the mediating effect of the PSSS on the relationship between the TFI and the SPBS in elderly patients with diabetes was 0.296 (95% CI: 0.007, 0.066), and the mesomeric effect accounted for 17.3% of the total effect.Conclusion: The debilitation of elderly patients with diabetes can be reduced by decreasing their SPB through perceived social support. This can be achieved through comprehensive interventions by nurses.Keywords: elderly patients with diabetes, frailty, self-perceived burden, mediating effects

Jian-Jun Wu,1 Ping-An Zhang,1 Ming-Zhe Chen,2 Yi Zhang,1 Wei-Sha Du,1 Xiao-Ning Li,1 Guo-Chao Ji,1 Liang-Duo Jiang,3 Yang Jiao,4,&ast; Xin Li5,&ast; 1Respiratory Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Infectious Disease Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3Respiratory Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Respiratory Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Glaucoma Department, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Li, Glaucoma Department, Eye Hospital, China academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email doudou8295@163.comBackground: Some patients with chronic obstructive pulmonary disease (COPD) benefit from glucocorticoid (GC) treatment, but its mechanism is unclear.Objective: With the help of the Gene Expression Omnibus (GEO) database, the key genes and miRNA-mRNA related to the treatment of COPD by GCs were discussed, and the potential mechanism was explained.Methods: The miRNA microarray dataset (GSE76774) and mRNA microarray dataset (GSE36221) were downloaded, and differential expression analysis were performed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs). The protein interaction network of the DEGs in the regulatory network was constructed with the STRING database, and the key genes were screened through Cytoscape. Potential downstream target genes regulated by differentially expressed miRNAs (DEMs) were predicted by the miRWalk3.0 database, and miRNA-mRNA regulatory networks were constructed. Finally, some research results were validated.Results: ① Four DEMs and 83 DEGs were screened; ② GO and KEGG enrichment analysis mainly focused on the PI3K/Akt signalling pathway, ECM receptor interaction, etc.; ③ CD2, SLAMF7, etc. may be the key targets of GC in the treatment of COPD; ④ 18 intersection genes were predicted by the mirwalk 3.0 database, and 9 pairs of miRNA-mRNA regulatory networks were identified; ⑤ The expression of miR-320d-2 and TFCP2L1 were upregulated by dexamethasone in the COPD cell model, while the expression of miR-181a-2-3p and SLAMF7 were downregulated.Conclusion: In COPD, GC may mediate the expression of the PI3K/Akt signalling pathway through miR-181a-2-3p, miR-320d-2, miR-650, and miR-155-5p, targeting its downstream signal factors. The research results provide new ideas for RNA therapy strategies of COPD, and also lay a foundation for further research.Keywords: COPD, GC, GEO database, miRNA-mRNA, DEMs, DEGs

Suthershinii G,1,&ast; Weiling Amanda Tan,2,&ast; Ainsley Ryan Yan Bin Lee,2 Matthew Zhixuan Chen3 1Department of Biological Sciences, National University of Singapore, Singapore, Singapore; 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 3Division of Geriatric Medicine, Department of Medicine, National University Hospital, Singapore&ast;These authors contributed equally to this workCorrespondence: Matthew Zhixuan Chen, Division of Geriatric Medicine, Department of Medicine, National University Hospital, 1E Kent Ridge Road, Tower Block, Level 10 Department of Medicine, 119228, Singapore, Tel +65 6779 5555, Email zhixuan_matthew_chen@nuhs.edu.sgBackground: Chronic heart failure (CHF) is a debilitating condition that affects millions worldwide. It is accompanied by a myriad of adverse consequences, such asdiminishing of quality of life and deterioration of mental health. Caregivers play a pivotal role in helping CHF patients manage their conditions and symptoms, as a result the physical, mental and emotional state of caregivers have a direct impact on CHF patients and the management of this condition.Purpose: This systematic review aims to synthesize data about the effectiveness of behavioral interventions targeted at patients with chronic heart failure (CHF) and/or informal caregivers of CHF patients to improve overall management and treatment of CHF in the population.Patients and Methods: Three databases were searched for published studies and studies that included evaluated outcomes of interventions that targeted CHF patients or informal caregivers. All randomized controlled trials, trials of either experimental or quasi-experimental design were included. Studies that only involved formal caregivers, patient populations of adolescents/young adults and patients with non-chronic conditions were excluded.Results: Across the 21 included studies, no study reported a significant improvement in all three domains of quality of life (QoL), depression and loneliness of caregivers while only three studies reported a significant improvement in two outcomes. Within each domain, heterogeneity in measures limited quantitative pooling.Conclusion: This review provides data on the efficacy of interventions targeted at CHF patients and/or informal caregivers. It also highlights successful interventions and its features. Following this, additional resources need to be invested and directed towards implementing these interventions.Keywords: caregiver burden, chronic care, multidisciplinary care, psychosocial

Background: Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV incidence in men.Methods: 4996 uncircumcised, HIV-negative men aged 15-49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00425984.Findings: Baseline characteristics of the men in the intervention and control groups were much the same at enrollment. Retention rates were much the same in the two groups, with 90-92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0.66 cases per 100 person-years in the intervention group and 1.33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16-72; p=0.006). The as-treated efficacy was 55% (95% CI 22-75; p=0.002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30-77; p=0.003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3.6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up.Interpretation: Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men. [ABSTRACT FROM AUTHOR]

Background: Haemorrhoids remain a highly prevalent condition in Australia, affecting 39% of the adult Australian population. While haemorrhoidectomy remains the gold standard in the management of haemorrhoids, newer techniques such as haemorrhoid artery ligation-recto anal repair (HAL-RAR) are emerging as promising management modalities. We compare the efficacy of non-Doppler guided (non-DG) HAL-RAR versus Doppler-guided (DG) HAL-RAR in the management of haemorrhoids., Methods: This study was registered with PROSPERO (CRD42022353806) and adhered to PRISMA 2020 guidelines. We conducted a systematic review using Medline, Embase and Cochrane database for comparative studies between Doppler-guided HAL-RAR and non-Doppler-guided HAL-RAR in accordance with the PRISMA 2020 statement for reporting systematic reviews., Results: Five studies were included in our systematic review and meta-analysis. There was no clinically significant difference in operative times (SMD 0.46, 9% CI -3.16 0 4.08, P = 0.804) or post-operative bleeding (P = 0.142) between the two groups. DG HAL-RAR patients were more likely to have post-operative urinary retention (P < 0.001). Non-DG patients were less likely to experience recurrence (OR 5.12, P < 0.001)., Conclusion: Our review of non-DG HAL-RAR compared to DG HAL-RAR reflects the non-inferiority of the non-DG HALRAR procedure. We hope that these results would provide a guide to clinicians performing HAL-RAR, and would provide some cost savings for institutions who are unable to procure the necessary equipment for DG HAL-RAR., (© 2024 Royal Australasian College of Surgeons.)

Background: Healthcare providers have faced challenges for patients with moderate and severe chronic obstructive pulmonary disease (COPD) in conducting their pulmonary rehabilitation due to dyspnea and exercise intolerance. Neuromuscular electrical stimulation (NMES) has been used to improve the muscle group's power and endurance without adding pulmonary workload, which might be used as a potential adjuvant rehabilitation method and thus to improve patients' pulmonary functions., Methods: This was a systematic review and meta-analysis of randomized controlled trials. Data were retrieved from PubMed, CINAHL, Academic Search Complete, Cochrane Library, and Airiti Library databases from the inception of the database to December 2022. The Cochrane Collaboration tool was used to assess the risk of bias. Two reviewers independently assessed, extracted, and appraised the included studies. Then, the grading of recommendations, assessment, development, and evaluation (GRADE) methodology was used for assessing the certainty of evidence. The pooled estimates were calculated using a random-effects model., Results: In total, 19 studies involving 589 moderate to severe COPD patients were analyzed. Compared with controls, adding NMES to pulmonary rehabilitation could significantly increase exercise capacity, physical activity function, and health-related quality of life (HRQoL) (all p < 0.05). The GRADE results showed low to very low certainty of evidence levels., Conclusion: NMES could improve exercise capacity and reduce the perceived sensation of dyspnea during exercise and is recommended as an effective adjuvant training modality in the rehabilitation for moderate to severe COPD patients., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest in this study., (Copyright © 2024. Published by Elsevier Ltd.)

Fibroblast growth factor 21 (FGF21) is a promising target for treatment of obesity-associated diseases including metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. We evaluated the effects of the bispecific anti-FGF21-β klotho (KLB) agonist antibody bFKB1 in a preclinical model of MASH and atherosclerosis. Low-density lipoprotein receptor knockout (Ldlr-/-).Leiden mice received a high-fat diet for 20 weeks, followed by treatment with an isotype control antibody or bFKB1 for 12 weeks. Effects on plasma risk markers and (histo)pathology of liver, adipose tissue, and heart were evaluated alongside hepatic transcriptomics analysis. bFKB1 lowered body weight (-21%) and adipose tissue mass (-22%) without reducing food intake. The treatment also improved plasma insulin (-80%), cholesterol (-48%), triglycerides (-76%), alanine transaminase (ALT: -79%), and liver weight (-43%). Hepatic steatosis and inflammation were strongly reduced (macrovesicular steatosis -34%; microvesicular steatosis -100%; inflammation -74%) and while the total amount of fibrosis was not affected, bFKB1 did decrease new collagen formation (-49%). Correspondingly, hepatic transcriptomics and pathway analysis revealed the mechanistic background underlying these histological improvements, demonstrating broad inactivation of inflammatory and profibrotic transcriptional programs by bFKB1. In epididymal white adipose tissue, bFKB1 reduced adipocyte size (-16%) and inflammation (-52%) and induced browning, signified by increased uncoupling protein-1 (UCP1) protein expression (8.5-fold increase). In the vasculature, bFKB1 had anti-atherogenic effects, lowering total atherosclerotic lesion area (-38%). bFKB1 has strong beneficial metabolic effects associated with a reduction in hepatic steatosis, inflammation, and atherosclerosis. Analysis of new collagen formation and profibrotic transcriptional programs indicate that bFKB1 treatment may have antifibrotic potential in a longer treatment duration as well., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: The optimal surgical technique for treating tibial plateau fractures remains controversial. This study aimed to compare the outcomes of arthroscopy-assisted reduction and internal fixation (ARIF) to those of open reduction and internal fixation (ORIF) in treating tibial plateau fractures., Methods: This systematic review and meta-analysis were conducted to compare surgical outcomes between ARIF versus ORIF for patients with tibial plateau fractures. Relevant studies, comprising randomized controlled trials (RCTs) and non-RCTs, were identified through searches in Cochrane CENTRAL, PubMed, and Embase databases. Risk of bias assessments were conducted using the revised Cochrane risk-of-bias tool for RCTs (RoB 2.0), Newcastle Ottawa scales for non-RCTs, and Joanna Briggs Institute Critical Appraisal Checklist for case series studies. Data synthesis utilized a random-effects model meta-analysis. The primary outcome assessed was functional outcomes, with complications considered as secondary outcomes., Results: There were fifteen studies (one RCT and fourteen non-RCTs) included in this study, comprising a total of 969 participants (548 in the ARIF group and 421 in the ORIF group). Although patients in the ARIF group showed a trend towards better functional outcomes compared to the ORIF group, the difference was not statistically significant (Hospital for special surgery score, mean difference (MD) = 5.13, 95% confidence interval (CI)=-1.67 to 11.92, I²=83%; Knee society score, MD = 5.84, 95% CI=-1.18 to 12.86, I²=74%). No significant differences were noted in infection, stiffness, DVT, and overall complications between two groups. The ARIF group included ten case series studies with a total of 302 patients. The pooled mean Rasmussen Radiological Score was 16.59 (95% CI, 15.72 to 17.50), and the pooled mean Rasmussen Clinical Score was 27.38 (95% CI, 26.45 to 28.33)., Conclusion: The findings of this study reveal no significant difference in clinical outcomes and complication rates between ARIF and ORIF. Additionally, this study found that the complication rate for patients undergoing ARIF falls within previously reported ranges. This suggests that ARIF is a reliable and effective surgical option for treating tibial plateau fractures, even in cases involving high-energy trauma., (© 2024. The Author(s).)

Background: To evaluate if comprehensive geriatric assessment (CGA)-guided care improves health-related quality of life (HRQL) in older adults with cancer compared to usual care., Methods: Relevant randomized controlled trials (RCTs) were identified through biomedical databases. Meta-analyses using DerSimonian-Laird model summarized the difference in the mean change of HRQL scores from baseline across various time points, with evidence certainty assessed by the GRADE tool. Logistic regression via generalized estimating equations analyzed predictors of HRQL improvement., Results: Potential improvement in the global HRQL score by CGA-guided care at 3 months (Cohen's d 0.27, 95 % CI -0.03-0.58, moderate certainty), could not be excluded. Larger RCTs or those mandating CGA before initiating anti-cancer treatment were predictors of improved HRQL., Conclusion: The effects of CGA-guided care on HRQL were variable. Larger RCTs and those mandating pre-treatment CGA tended to report improved HRQL., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aimed to analyze the effect of proximal neck angulation on the biomechanical indices of abdominal aortic aneurysms (AAA) and to investigate its impact on the risk of AAA rupture., Methods: CT angiography (CTA) data of patients with AAA from January 2015 to January 2022 were collected. Patients were divided into three groups based on the angle of the proximal neck: Group A (∠β ≤ 30°), Group B (30°<∠β ≤ 60°), and Group C (∠β > 60°). Biomechanical indices related to the rupture risk of AAA were analyzed using computational fluid dynamics modeling (CFD-Post) based on the collected data., Results: Group A showed slight turbulence in the AAA lumen with a mixed laminar flow pattern. Group B had a regular low-speed eddy line characterized by cross-flow dominated by lumen blood flow and turbulence. In Group C, a few turbulent lines appeared at the proximal neck, accompanied by eddy currents in the lumen expansion area following the AAA shape. Significant differences were found in peak wall stress, shear stress, and the maximum blood flow velocity impact among the three groups. The maximum blood flow velocity at the angle of the proximal neck impact indicated the influence of the proximal neck angle on the blood flow state in the lumen., Conclusion: As the angle of the proximal neck increased, it caused stronger eddy currents and turbulent blood flow due to a high-speed area near the neck. The region with the largest diameter in the abdominal aortic aneurysm was prone to the highest stress, indicating a higher risk of rupture. The corner of the proximal neck experienced the greatest shear stress, potentially leading to endothelial injury and further enlargement of the aneurysm., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight., Methods: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis., Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-I and APO A-II, were confirmed using enzyme-linked immunosorbent assay., Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: We investigated whether double-bundle (DB) anterior cruciate ligament (ACL) reconstruction (ACLR) combined with anterolateral ligament reconstruction (ALLR) improved clinical and radiological outcomes in patients at high risk of ACL failure. The primary outcome was graft failure, and secondary outcomes included knee stability and patient-reported outcome measures (PROMs)., Patients and Methods: Fifty-two patients who underwent DB ACLR combined with ALLR were included in this retrospective cohort study. Preoperative risk factors, including femorotibial angle (FTA), lateral tibial slope (LTS), medial tibial slope (MTS), and meniscal tears, were assessed using X-ray and magnetic resonance imaging (MRI). The grade of post-operative pivot shift, Lysholm score, and Tegner activity score were used to assess clinical outcomes. The minimum follow up duration was 2 years., Results: The cohort (mean age, 26.1 ± 9.4 years; 51.9% male) had a mean follow-up duration of 28.9 ± 3.4 months. Preoperatively, 57.8% had lateral meniscus (LM) tears, and 61.0% had a grade 2-3 pivot shift. Postoperatively, no graft failures or revision cases occurred during follow-up. Approximately 90.4% of the patients exhibited a negative pivot shift (p < 0.001), with Lysholm and Tegner activity scores of 92.5 ± 6.1 and 5.1 ± 2.0. The medial meniscus (MM) tear group had a significantly smaller FTA than the intact group (p = 0.043). No significant differences in PROMs were found between the LM tear and intact LM groups or between the high and low MTS or LTS groups (p = n.s.)., Conclusion: DB ACLR combined with ALLR had satisfactory clinical outcomes in patients at high risk of ACL failure, with no graft failures observed during a mean follow-up duration of 2.4 years. The technique effectively reduced the postoperative pivot shift, regardless of preoperative risk factors., Study Design: Level IV, retrospective therapeutic case-series., Trail Registration: ethical approval number, 202300134B0; ethical committee, the Institutional Review Board of Chang Gung Medical Foundation., (© 2024. The Author(s).)

A convenient method for the synthesis of perdeuterated alkyl amides/amines is disclosed. Perdeuterated acetyl amides can be achieved by a hydrogen-deuterium (H/D) exchange protocol with Pt/C as a catalyst and D 2 O as a deuterium source under mild conditions. After removal or reduction of the acetyl group, this protocol can provide perdeuterated primary, secondary, and tertiary amines, which are difficult to achieve via other methods.

Current human health risk assessments of soil arsenic (As) contamination rarely consider bioaccessibility (IVBA), which may overestimate the health risks of soil As. The IVBA of As (As-IVBA) may differ among various soil types. This investigation of As-IVBA focused As from geological origin in a typical subtropical soil, lateritic red soil, and its risk control values. The study used the SBRC gastric phase in vitro digestion method and As speciation sequential extraction based upon phosphorus speciation extraction method. Two construction land sites (CH and HD sites) in the Pearl River Delta region were surveyed. The results revealed a high content of residual As (including scorodite, mansfieldite, orpiment, realgar, and aluminum arsenite) in the lateritic red soils at both sites (CH: 84.9%, HD: 91.7%). The content of adsorbed aluminum arsenate (CH: 3.24%, HD: 0.228%), adsorbed ferrum arsenate (CH: 8.55%, HD: 5.01%), and calcium arsenate (CH: 7.33%, HD: 3.01%) were found to be low. The bioaccessible As content was significantly positively correlated with the As content in adsorbed aluminum arsenate, adsorbed ferrum arsenate, and calcium arsenate. A small portion of these sequential extractable As speciation could be absorbed by the human body (CH: 14.9%, HD: 3.16%), posing a certain health risk. Adsorbed aluminum arsenate had the highest IVBA, followed by calcium arsenate, and adsorbed ferrum arsenate had the lowest IVBA. The aforementioned speciation characteristics of As from geological origin in lateritic red soil contributed to its lower IVBA compared to other soils. The oxidation state of As did not significantly affect As-IVBA. Based on As-IVBA, the carcinogenic and non-carcinogenic risks of soil As in the CH and HD sites decreased greatly in human health risk assessment. The results suggest that As-IVBA in lateritic red soil should be considered when assessing human health risks on construction land., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Older adults make up half of those with cancer and are prone to mood disorders, such as depression and severe anxiety, resulting in negative repercussions on their health-related quality-of-life (HRQOL). Educational interventions have been shown to reduce adverse psychological outcomes. We examined the effect of educational interventions on the severity of psychological outcomes in older adults with cancer (OAC) in the community., Method: This PRISMA-adherent systematic review involved a search of PubMed, MedLine, Embase and PsycINFO for randomised controlled trials (RCTs) that evaluated educational interventions impacting the severity of depression, anxiety and HRQOL in OAC. Random effects meta-analyses and meta-regressions were used for the primary analysis., Results: Fifteen RCTs were included. Meta-analyses showed a statistically insignificant decrease in the severity of depression (SMD = -0.30, 95%CI: -0.69; 0.09), anxiety (SMD = -0.30, 95%CI: -0.73; 0.13) and improvement in overall HRQOL scores (SMD = 0.44, 95%CI: -0.16; 1.04). However, subgroup analyses revealed that these interventions were particularly effective in reducing the severity of depression and anxiety in specific groups, such as OAC aged 60-65, those with early-stage cancer, those with lung cancer and those treated with chemotherapy. A systematic review found that having attained a higher education and income level increased the efficacy of interventions in decreasing the severity of adverse psychological outcomes., Conclusion: Although overall meta-analyses were statistically insignificant, subgroup meta-analyses highlighted a few specific subgroups that the educational interventions were effective for. Future interventions can be implemented to target these vulnerable groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objectives: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years., Methods: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes., Results: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life)., Conclusions: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes., Clinical Trial Registration: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838., Citation: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med . 2024;20(6):947-957., (© 2024 American Academy of Sleep Medicine.)

To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The incidence and mortality of cancer is increasing worldwide with studies reporting that cumulative risk of cancer rises as age increases. Against the backdrop of the increasing prevalence of cancer amongst older patients, we conducted a systematic review and meta-analysis examining the depression-mortality relationship in older adults with cancer (OAC)., Materials and Methods: This PRISMA-adherent systematic review involved a systematic search of PubMed, Medline, EMBASE, and PsycINFO for prospective and retrospective cohort studies comparing the risk of all-cause and cancer-related mortality among OAC with depression. Random effects meta-analyses and meta-regressions were used for the primary analysis., Results: From 5,280 citations, we included 14 cohort studies. Meta-analyses of hazard ratios (HRs) showed an increased incidence of all-cause mortality in OAC with depression (pooled HR: 1.40; 95% confidence interval [CI]: 1.25, 1.55). Subgroup analyses of other categorical study-level characteristics were insignificant. While risk of cancer-related mortality in OAC with depression was insignificantly increased with a pooled HR of 1.21 (95% CI: 0.98, 1.49), subgroup analysis indicated that risk of cancer-related mortality in OAC with depression significantly differed with cancer type. Our systematic review found that having fewer comorbidities, a higher education level, greater socioeconomic status, and positive social supportive factors lowered risk of all-cause mortality in OAC with depression., Discussion: Depression in OAC significantly increases risk of all-cause mortality and cancer-related mortality among different cancer types. It is imperative for healthcare providers and policy makers to recognize vulnerable subgroups among older adults with cancer to individualize interventions., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any personal, commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: This study investigated the clinical risk factors for peripheral neuropathy induced by docetaxel and albumin-bound paclitaxel (AP) in patients with breast cancer., Methods: This prospective observational study recruited 268 patients between March 2019 and December 2020. Patient information was obtained through the query system for laboratory test results, patient consultations, and scale evaluations. Neuropathic symptoms were followed up throughout and until 3 months after taxane chemotherapy. Univariate and multivariate analyses were used to find the risk factors for overall and moderate-severe taxane-induced peripheral neuropathy (TIPN)., Results: Cumulative dose (odds ratio [OR] = 3.533, 95% confidence interval [CI]: 1.797-6.944, p < 0.001), body mass index (BMI) (OR = 2.926, 95% CI: 1.621-5.281, p < 0.001), body surface area (BSA) (OR = 1.724, 95% CI: 1.011-2.941, p = 0.045), and hypocalcemia (OR = 4.899, 95% CI: 1.518-15.811, p = 0.008) all increased the risk of TIPN. Only cumulative dose (OR = 2.577, 95% CI: 1.161-5.719, p = 0.020) and BSA (OR = 2.040, 95% CI: 1.073-3.877, p = 0.030) were independent risk factors for moderate-severe TIPN., Conclusion: Cumulative dose, BMI, BSA, and hypocalcemia are all risk factors for overall TIPN, whereas cumulative dose and BSA are risk factors for moderate-severe TIPN. Patients with breast cancer who have high BMI, large BSA, hypocalcemia, and large cumulative dose may be at risk of TIPN, and intervention measures must be actively carried out for them., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: Jinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of human histone deacetylase-2 (HDAC2). However the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear., Objective: To explore the target of Jinwei decoction to enhance the anti-inflammatory effect of GC on COPD through microRNA155-5p (miR-155-5p) by network pharmacology and experimental verification., Methods: The TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-155-5p. COPD-related genes were identified by searching GeneCards, Grugbank and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. A COPD cell model was established by 5% cigarette smoke extract (CSE)- induced bronchial epithelial cell (BEAS-2B), and the results of network pharmacology were verified by in vitro experiments., Results: Two hundred thirty-one active ingredients, 352 Jinwei decoction drug targets, 5949 miR-155-5p target genes, 8286 COPD target genes, and 127 intersection genes were identified. Twelve core proteins of PPI networks may be involved. GO enrichment analysis showed that regulation of membrane potential， response to steroid hormone, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, and other signaling pathways. The molecular docking results showed that quercetin, luteolin and stigmasterol have higher affinity with PTGS2, HIF1A and AKT1. The results of cell experiments revealed that Jinwei decoction not only enhances the anti- inflammatory effect of GC in the COPD cell model but also reverses the high expression of miR-155-5p、PI3k、Akt, and low expression of HDAC2, thereby inhibiting the inflammatory response of COPD., Conclusion: Jinwei decoction can regulate HDAC2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-155-5p. Its mechanism of action may be related to its effect on the PI3K-Akt through miR-155-5p., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A sensitive, robust, and highly efficient analytical methodology involving solid phase extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry was successfully established to detect 13 monoalkyl phthalate esters (MPAEs) in aquatic organisms and seawater. After the organisms were preprocessed using enzymatic deconjugation with β-glucuronidase, extraction, purification, and qualitative and quantitative optimization procedures were performed. Under optimal conditions, the limits of detection varied from 0.07 to 0.88 μg/kg (wet weight) and 0.04-1.96 ng/L in organisms and seawater, respectively. Collectively, MPAEs achieved acceptable recovery values (91.0-102.7%) with relative standard deviations less than 10.4% and matrix effects ranging from 0.93 to 1.07 in the above matrix. Furthermore, MPAEs and phthalate esters were detected by the developed methodology and gas chromatography-triple quadrupole tandem mass spectrometer in practical samples, respectively. Mono-n-butyl phthalate and mono-iso-butyl phthalate were the most predominant congeners, accounting for 24.8-35.2% in aquatic organisms and seawater. Comprehensive health and ecological risks were higher after the MPAEs were incorporated than when phthalate esters were considered separately, and greater than their risk threshold. Therefore, the risks caused by substances and their metabolites in multiple media, with analogous structure-activity relationships, should be considered to ensure the safety of aquatic organisms and consumers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The ability to target specific tissues and to be internalized by cells is critical for successful nanoparticle-based targeted drug delivery. Here, we combined "stealthy" rod-shaped poly(2-oxazoline) (POx) nanoparticles of different lengths with a cancer marker targeting nanobody and a fluorescent cell internalization sensor via a heat-induced living crystallization-driven self-assembly (CDSA) strategy. A significant increase in association and uptake driven by nanobody-receptor interactions was observed alongside nanorod-length-dependent kinetics. Importantly, the incorporation of the internalization sensor allowed for quantitative differentiation between cell surface association and internalization of the targeted nanorods, revealing unprecedented length-dependent cellular interactions of CDSA nanorods. This study highlights the modularity and versatility of the heat-induced CDSA process and further demonstrates the potential of POx nanorods as a modular nanomedicine platform.

Background: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA)., Methods: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded., Results: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication., Conclusions: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects., Trial Registration: ISRCTN34355813. Registered on 25/01/2021., (© 2024. The Author(s).)

The use of patient-derived xenografts (PDXs) in cancer research is increasing due to their ability to closely mimic the features of patient tumors. The ability to quickly and robustly measure protein expression levels in these tissues is a key methodology required in a broad range of experimental designs. Western blotting (WB) is a cost effective and simple tool that is highly specific and sensitive for detecting and quantifying individual proteins, posttranslational modifications and aberrant signaling pathways. Here, we described a method to assess protein expression in PDX tissues using WB to detect proteins involved in cell growth signaling pathways., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Breast cancer, especially the aggressive triple-negative subtype, poses a serious health threat to women. Unfortunately, effective targets are lacking, leading to a grim prognosis. Research highlights the crucial role of c-MYC overexpression in this form of cancer. Current inhibitors targeting c-MYC focus on stabilizing its G-quadruplex (G4) structure in the promoter region. They can inhibit the expression of c-MYC , which is highly expressed in triple-negative breast cancer (TNBC), and then regulate the apoptosis of breast cancer cells induced by intracellular ROS. However, the clinical prospects for the application of such inhibitors are not promising. In this research, we designed and synthesized 29 acridone derivatives. These compounds were assessed for their impact on intracellular ROS levels and cell activity, followed by comprehensive QSAR analysis and molecular docking. Compound N 8 stood out, significantly increasing ROS levels and demonstrating potent anti-tumor activity in the TNBC cell line, with excellent selectivity shown in the docking results. This study suggests that acridone derivatives could stabilize the c-MYC G4 structure. Among these compounds, the small molecule N 8 shows promising effects and deserves further investigation.

Approximately 1%-2% of patients with colorectal cancer (CRC) develop para-aortic lymph node (PALN) metastases, which are typically considered markers of systemic disease, and are associated with a poor prognosis. The utility of PALN dissection (PALND) in patients with CRC is of ongoing debate and only small-scale retrospective studies have been published on this topic to date. This systematic review aimed to determine the utility of resecting PALN metastases with the primary outcome measure being the difference in survival outcomes following either surgical resection or non-resection of these metastases. A comprehensive systematic search was undertaken to identify all English-language papers on PALND in the PubMed, Medline, and Google Scholar databases. The search results identified a total of 12 eligible studies for analysis. All studies were either retrospective cohort studies or case series. In this systematic review, PALND was found to be associated with a survival benefit when compared to non-resection. Metachronous PALND was found to be associated with better overall survival as compared to synchronous PALND, and the number of PALN metastases (2 or fewer) and a pre-operative carcinoembryonic antigen level of <5 was found to be associated with a better prognosis. No PALND-specific complications were identified in this review. A large-scale prospective study needs to be conducted to definitively determine the utility of PALND. For the present, PALND should be considered within a multidisciplinary approach for patients with CRC, in conjunction with already established treatment regimens., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: In the most severe stage of endometriosis, Stage IV, intestinal involvement is common. The true prevalence of endometriotic disease of the appendix in this population is not well described. A macroscopically normal looking appendix may harbour endometriosis., Aims: Our study aims to assess the role of routinely performing appendicectomy in Stage IV endometriosis surgery, and the histopathological prevalence of true appendiceal endometriosis in this population., Methods: This is a retrospective study of women undergoing surgery for Stage IV endometriosis between 2018 to 2022 in a tertiary public hospital in New South Wales, Australia. Patient demographics, age and post-operative complications were retrospectively retrieved from hospital medical records. Inclusion criteria were women with Stage IV endometriosis who underwent routine appendicectomy as part of their endometriosis surgery. Exclusion criteria were women who did not have Stage IV endometriosis, those who had cancer surgery or emergency surgery for endometriosis. The primary outcome of this study was to determine the incidence of appendiceal endometriosis. Secondary outcomes included post-operative complications and length of stay., Results: Sixty-seven patients were included. The mean age was 36 years. All patients also underwent bowel resection for colorectal endometriosis. There were 35.8% who had confirmed appendiceal endometriosis on histopathology. Post-operative complications included port site infections, colitis, urinary tract infection and ureteric injury. There were no complications related to appendicectomy. Mean length of stay was 4.4 days., Conclusion: Laparoscopic appendicectomy can be safely performed at time of laparoscopic surgical excision of Stage IV endometriosis and should be routinely considered in a subset of Stage IV endometriosis patients with colorectal involvement undergoing surgery., (© 2023 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance( P =0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog&#95;Macro2 and Prog&#95;Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks( P <0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.

Background: With increasing life expectancy, there is an increasing proportion of nonagenarians undergoing both elective and emergency surgical procedures. The decision as to whom will benefit from surgical procedures is however difficult to ascertain and still remains a challenge to clinicians. This study is aimed to evaluate the clinical outcomes of colonoscopy in the nonagenarian population, and to determine if the outcomes are acceptable for us to continue to offer such interventions., Methods: Retrospective study of patients of Dr. G.R (Gastroenterologist) and Dr. W.B (Colorectal Surgeon) between 1 January 2018 and 31 November 2022. All patients who were ≥90 years old and had a colonoscopy was included in the study. Exclusion criteria were patients who were less than 90 years old, had a flexible sigmoidoscopy or colonoscopy as part of their surgical procedure., Primary Outcome Measures: post-colonoscopy complications and length of stay., Secondary Outcome Measures: reasons for colonoscopy, significant colonoscopy findings, 30-day morbidity and mortality., Results: Sixty patients were included in the study. Median age was 91 (90-100) years old. 33.3% of the patients were males. Seventy percent of the patients were ASA 3. Median length of hospital stay was 1 day. 11.7% of patients were found to have colorectal malignancy. There were no complications after the colonoscopy. There were no 30-day re-admission, morbidity or mortality., Conclusion: Colonoscopy can be performed safely in carefully selected nonagenarian patients with acceptable low complication rates., (© 2023 Royal Australasian College of Surgeons.)

Glassy and liquid state metal-organic frameworks (MOFs) are emerging type of materials subjected to intense research for their rich physical and chemical properties. In this report, we obtained the first glassy MOF that involves metal-carboxylate cluster building units via multi-stage structural transformations. This MOF is composed of linear [Mn 3 (COO) 6 ] node and flexible pyridyl-ethenylbenzoic linker. The crystalline MOF was first perturbed by vapor hydration and thermal dehydration to give an amorphous state, which can go through a glass transition at 505 K into a super-cooled liquid. The super-cooled liquid state is stable through a wide temperature range of 40 K and has the largest fragility index of 105, giving a broad processing window. Remarkably, the super-cooled liquid can not only be quenched into glass, but also recrystallize into the initial MOF when heated to a higher temperature above 558 K. The mechanism of the multi-stage structural transformations was studied by systematic characterizations of in situ X-ray diffraction, calorimetry, rheological, spectroscopic and pair-distribution function analysis. These multi-stage transformations not only represent a rare example of high temperature coordinative recognition and self-assembly, but also provide new MOF processing strategy through crystal-amorphous-liquid-crystal transformations., (© 2023 Wiley-VCH GmbH.)

Objective: To investigate the association between the prevalence of cyclosporin A-induced gingival overgrowth and the expression of the epithelial-to-mesenchymal transition factors in the gingival tissues of renal transplant patients., Background: Gingival overgrowth (GO) is a frequent complication in organ transplant patients treated with the immunosuppressant cyclosporin A (CsA). The epithelial-to-mesenchymal transition (EMT) is considered a factor contributing to CsA-induced GO. However, current knowledge on this topic is sparse., Methods: Sixty-three renal transplant patients were divided into two groups according to the occurrence of GO: those with gingival overgrowth (GO+ group) and those without gingival overgrowth (GO- group). Data on age, sex, and use of immunosuppressant and calcium channel blocker medications, serum creatinine values, peak concentrations of blood CsA, and gingival hyperplasia scores were recorded to identify clinically pathogenic factors. Gingival tissues from five patients with CsA-induced GO and five healthy subjects were selected for histomorphological observation with hematoxylin-eosin staining, Masson staining, and immunohistochemical staining. The mRNA expression of EMT factors was detected with reverse transcription-quantitative PCR., Results: The use of CsA significantly increased the prevalence of GO in renal transplant patients. The expression of α-SMA, SMAD4, and TGM2 was upregulated and that of E-cadherin was downregulated in the gingival tissues of patients with CsA-induced GO compared with those of the corresponding controls., Conclusion: Treatment with CsA is closely related to the occurrence of GO in renal transplant patients and EMT plays an important role in CsA-induced gingival tissue hyperplasia., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Reticular chemistry provides opportunities to design solid-state electrolytes (SSEs) with modular tunability. However, SSEs based on modularly designed crystalline metal-organic frameworks (MOFs) often require liquid electrolytes for interfacial contact. Monolithic glassy MOFs can have liquid processability and uniform lithium conduction, which is promising for the reticular design of SSE without liquid electrolytes. Here, we develop a generalizable strategy for the modular design of noncrystalline SSEs based on a bottom-up synthesis of glassy MOFs. We demonstrate such a strategy by linking polyethylene glycol (PEG) struts and nanosized titanium-oxo clusters into network structures termed titanium alkoxide networks (TANs). The modular design allows the incorporation of PEG linkers with different molecular weights, which give optimal chain flexibility for high ionic conductivity, and the reticular coordinative network provides a controlled degree of cross-linking that gives adequate mechanical strength. This research shows the power of reticular design in noncrystalline molecular framework materials for SSEs.

Introduction: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship., Methods and Materials: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes., Results: There were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN., Conclusion: More than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To systematically evaluate the risk factors of depression and anxiety in older adults with cancer., Method: This PRISMA-adherent systematic review (PROSPERO CRD42022372747) involved a systematic database search for prospective and retrospective cohort studies., Results: We included 33 cohort studies with 31 evaluating depression and seven evaluating anxiety. Systematic synthesis yielded various protective and exacerbating factors for depression and anxiety amongst older adults with cancer. These factors span a range of domains: (1) Cancer and associated treatment-related factors; (2) Medical, physical and functional factors; (3) Demographic factors and; (4) Social and lifestyle factors. At the individual-level, the most significant factors were the presence of chronic medical comorbidities, having pre-existing psychological symptoms, and poor baseline physical and functional status. Within the social unit, the degree of social support and presence of a partner were most significant., Conclusion: The deleterious impact comorbid psychological symptoms can have on older adults with cancer can be profound. In this review, we highlight a range of protective and exacerbating factors identified from cohort studies that may enable policymakers to tailor and individualise interventions to manage depression, anxiety and associated burden in this vulnerable population. The relative paucity of studies evaluating anxiety highlights an important research gap., Competing Interests: Declaration of Competing Interest 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 © 2023 Elsevier Inc. All rights reserved.)

Background: Accurate staging for rectal cancer is pertinent with recent introduction of rectum-sparing approaches for patients showing complete clinical response on restaging. Positron emission tomography(PET) is used in detection of recurrence or metastasis, but its value in routine preoperative rectal cancer staging remains unclear. Studies report that preoperative PET altered the stage in 39% and changed the management in 17-27% of patients. Our study aims to look at the utility of PET in routine preoperative staging of rectal cancer within 2 two colorectal units, and to determine if PET did result in a change in management., Methods: Patients in Nepean Hospital (NSW) and Peter MacCallum Cancer Centre (VIC) who were diagnosed with rectal cancer between 1 January 2017 and 31 December 2021 were included in this retrospective study. All patients who did not have a PET scan were excluded. PET scan results were then compared with MRI and CT results., Results: Three hundred and fifty-seven patients were included in the study. 30.3% of the patients had Stage 3 rectal cancer. 71.7% received neoadjuvant therapy. PET scan provided additional information in 55.5% of patients when compared with CT and MRI alone; 18.2% of the PET findings resulted in an altered management for the patient., Conclusion: PET scan can be a valuable tool in accurate staging, especially for ambiguous or equivocal lesions on CT. Our study demonstrated that additional information from PET scan resulted in an altered management plan in 18.2% of the patients. PET/MRI as a newer modality may be more accurate with reduced radiation exposure., (© 2022 Royal Australasian College of Surgeons.)

Introduction: Substance P (SP) is a neuropeptide released from the nervous fibers in response to injury. In addition to its association with pain and reactions to anxiety and stress, SP exerts various physiological functions by binding to the neurokinin-1 receptor (NK1R). However, the expression and role of SP in reparative dentinogenesis remain elusive. Here, we explored whether SP is involved in odontoblastic differentiation during reparative dentinogenesis., Methods: Dental pulp stem cells (DPSCs) were isolated from healthy human dental pulp tissues and subjected to odontoblastic differentiation. The expression of SP and NK1R during odontoblastic differentiation was investigated in vitro. The effects of SP on odontoblastic differentiation of DPSCs were evaluated using alizarin red staining, alkaline phosphatase staining, and real-time polymerase chain reaction. After direct pulp capping with mineral trioxide aggregate, the expression of SP and NK1R during reparative dentin formation in rats were identified using histological and immunohistochemical staining., Results: SP and NK1R expression increased during the odontoblastic differentiation of DPSCs. SP translocated to the nucleus when DPSCs were exposed to differentiation medium. NK1R was always present in the nuclei of DPSCs and odontoblast-like cells. Additionally, we discovered that 10 -8  M SP marginally enhanced the odontoblastic differentiation of DPSCs, and that these effects could be impaired by the NK1R antagonist. Furthermore, SP and NK1R were expressed in odontoblast-like and dental pulp cells during reparative dentin formation in vivo., Conclusions: SP contributes to odontoblastic differentiation during reparative dentin formation by binding to the NK1R., (Copyright © 2023. Published by Elsevier Inc.)

LncRNA CASC15 has been determined as a novel tumor-related lncRNA in many cancers. However, the in-detail role of CASC15 remains elusive in esophageal squamous cell carcinoma (ESCC). CASC15 expression level was detected in 113 ESCC tissues and paired adjacent normal tissues and in human ESCC cell lines. The effects of CASC15 on ESCC proliferation, migration, and invasion were assessed using CCK-8 and transwell assays. In addition, the potential downstream molecules of CASC15 were searched and confirmed by software algorithms, RT-qPCR, western blot, dual-luciferase reporter, and rescue experiments. CASC15 was upregulated in ESCC tissues and cell lines. CASC15 overexpression was associated with poorer prognosis in ESCC patients. Functionally, CASC15 knockdown inhibited cell proliferation, migration, and invasion of ESCC cells. Mechanistically, it was confirmed that CASC15 acts as competing endogenous RNA for miR-33a-5p to regulate PTGS2 expression. In addition, rescue assay showed that miR-33a-5p knockdown or PTGS2 overexpression abolished the cell proliferation, migration, and invasion inhibition role of CASC15 knockdown. In conclusion, this study indicates that CASC15 was upregulated in ESCC and CASC15 knockdown hindered ESCC progression through targeting the miR-33a-5p/PTGS2 axis. CASC15 might serve as a novel biomarker and therapeutic target for ESCC., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Objectives: Multicomponent exercise program have shown to improve function and cognition in older adults but studies on pre-frail older adults in the primary care setting are limited. This study aimed i) to evaluate impact of 6 months exercise (Ex) versus complementary effect of 3 months of cognitive stimulation therapy (CST) to 6 months of Ex (Ex+CST) on physical function, muscle mass and cognition versus control group at 3, 6 and 12 months ii) inflammatory biomarkers such as Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α)., Design: Cluster randomised control trial., Setting and Intervention: Pre-frail older adults ≥ 65 years attending primary care clinic. Two intervention groups i) Ex 6 months ii) CST 3 months with Ex 6 months., Measurements: At 0, 3, 6 and 12 months, questionnaires (on demographics, physical function, cognition, and depression) were administered and physical function assessment (gait speed, short physical performance battery (SPPB) test, handgrip strength, five times sit-to-stand (5x-STS)) was conducted. Muscle mass and its surrogates such as phase angle and body cell mass were measured using bioelectrical impedance analysis machine. Inflammatory biomarkers were measured at 0 and 3 months., Results: Data from 190 participants was analysed at 3 months (111 control, 37 Ex and 41 Ex+CST). At 3 months, significant improvement in cognition was seen only in the Ex+CST group whereas improvements in depression, gait speed, SPPB and 5x-STS were seen in both the Ex and Ex+CST groups. At 6 months, the Ex+CST group improved in cognition and depression whereas improvement in frailty and muscle mass indices were seen in both the interventions groups. At 12 months, both the interventions groups had better perceived health, gait speed and less decline in muscle mass compared with control groups. Both the Ex and Ex+CST had significant association with TNF-α at 3 months (β -2.71 (95% CI -4.80 - -0.62); p = 0.012 and β -1.74 (95% CI -3.43 - -0.06); p = 0.043 respectively)., Conclusion: Combined Ex+CST had significant improvement in cognition whereas the intervention groups improved in depression, physical function, muscle mass, frailty, perceived health and TNF-α levels. With growing evidence of the benefits of multicomponent interventions at primary care level, incorporating it into mainstream care with action plans on long-term sustainability and scalability should be a priority for every country., Competing Interests: The authors declare no conflict of interest.