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Abstract Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 109 to 5 × 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 109 and 1 × 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 1010vp). Therefore, the maximum tolerated dose was determined to be 1 × 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.

Abstract Purpose This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. Method The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. Results Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. Conclusion The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.

IntroductionData about the impact of varying physical-activity therapy (PAT) intensities and the ideal duration of cognitive behavioral therapy (CBT) on older adults is inadequate. In this umbrella review, we seek to comprehensively synthesize and analyze findings from systematic reviews and meta-analyses regarding the optimal PAT intensity for lowering FOF and the duration of CBT interventions for effectively lowering FOF.MethodsThe PubMed, Web of Science, Cochrane Library, Medline, Embase, and CINAHL databases were searched up to April 2024. AMSTAR 2 was applied to assess the methodological and reporting quality. The quality of evidence for each intervention’s effect was evaluated using GRADE guidelines. A further meta-analysis of the primary studies was conducted to evaluate the effects of PAT intensity and CBT duration.ResultsIn the 18 included studies, 12 were PAT interventions, 3 were multifactorial, and 3 were CBT interventions. The umbrella review found that PAT and CBT interventions can effectively manage FOF. Comparable improvements were reported with low- and moderate-intensity PAT intervention (p

IntroductionLuteolin, a naturally occurring flavonoid compound, demonstrates promising anti-cancer properties. However, its mechanism against non-small-cell lung cancer (NSCLC) remains unknown. This study employed network pharmacology, molecular docking, molecular dynamics simulation (MDS), and in vitro experiments to investigate the potential mechanisms by which luteolin against NSCLC.MethodsInitially, the potential targets of luteolin and NSCLC-related targets were identified from public databases such as TCMSP, GeneCards, OMIM, DrugBank, and TTD. Subsequently, the protein-protein interaction (PPI) network screening and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The binding affinity and stability of luteolin with the core targets were assessed using molecular docking and MDS. Finally, the results were validated by in vitro experiments.ResultsA total of 56 luteolin targets and 2145 NSCLC-related targets were identified. Six core targets, TP53, EGFR, AKT1, TNF, JUN, and CASP3, were screened via the PPI network. The GO and KEGG analyses indicated that luteolin’s activity against NSCLC potentially involves PI3K-Akt, NF-kappa B, and other signaling pathways. Molecular docking revealed that luteolin had high binding affinity with the core targets. MDS confirmed the stable interaction between luteolin and key proteins TP53 and AKT1. in vitro, luteolin significantly inhibited the proliferation and migration of A549 cells, while also inducing apoptosis. In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002.ConclusionLuteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway.

Abstract The aim of the study was to investigate the incidence, prevalence and characteristics of multimorbidity in urban inpatients of different age groups. This study used data from the National Insurance Claim for Epidemiology Research (NICER) to calculate the overall incidence, prevalence, geographic and age distribution patterns, health care burden, and multimorbidity patterns for multimorbidity in 2017. According to our study, the overall prevalence of multimorbidity was 6.68%, and the overall prevalence was 14.87% in 2017. The prevalence of multimorbidity increases with age. The pattern of the geographic distribution of multimorbidity shows that the prevalence of multimorbidity is relatively high in South East China. The average annual health care expenditure of patients with multimorbidity increased with age and rose rapidly, especially among older patients. Patients with cancer and chronic kidney disease have higher treatment costs. Patients with hypertension or ischemic heart disease had a significantly higher relative risk of multimorbidity than other included noncommunicable diseases (NCDs). Hyperlipidemia has generated the highest number of association rules, which may suggest that hyperlipidemia may be both a risk factor for other NCDs and an outcome of them.

Abstract Aim Exploring the influence of patient safety culture on nurses' pain and turnover intention the job as a second victim. Design The study employed a cross‐sectional design. Methods From July 2020 to August 2020, a convenience sampling method was used to select 1525 clinical nurses from hospitals of different levels in Shandong Province as the research subjects, and the general data survey method, patient safety culture scale and the assessment entries on pain in the second victim experience and support scale, using a convenience sampling method. Results Patient safety culture is an influencing factor that affects the second‐victim pain and turnover intention. Among them, the non‐punitive response to errors, open communication, cooperation between different departments, organizational learning and promotion has a statistically significant influence on the second‐victim pain and turnover intention.

BackgroundNeglect is a common form of abuse, and long-term care facilities record higher incidences of this abuse. Given that older adult care workers are the main workforce in these facilities, their neglectful behavior requires public health attention. Internal individual characteristics can lead to older adult abuse, and managing workers who abuse older adults may require various methods. This study aimed to identify the profiles of neglect among older adult care workers in long-term care facilities and explore the influencing factors of neglect.MethodsIn this cross-sectional study, a convenience sample of older adult care workers from 15 long-term care facilities in Shandong Province (N = 421) completed a questionnaire on the characteristics associated with neglect. Latent profile analysis was used to identify distinct neglect profiles and promote the understanding of individual characteristics associated with varying levels of neglect. One-way analysis of variance and multivariate logistic regression analyses were used to examine the population characteristic differences.ResultsOlder adult care workers exhibited three neglect profiles, namely, the “low-risk group,” “medium-risk group,” and “high-risk group.” Males, participants with no employment qualification certificate, and those who did not attend regular training represented the majority of those in the “high-risk group.” Participants with a monthly income of more than ¥ 4,000 and nursing 1–2 older adults simultaneously represented the majority of those in the “low-risk group.”ConclusionLong-term care facility administrators should tailor interventions to individual care worker profiles to reduce neglect behaviors and improve care levels.

Background. This research investigated whether glucose fluctuation (GF) can exacerbate cognitive impairment in streptozotocin-induced diabetic rats and explored the related mechanism. Methods. After 4 weeks of feeding with diets containing high fats plus sugar, the rat model of diabetes mellitus (DM) was established by intraperitoneal injection of streptozotocin (STZ). Then, GF was triggered by means of alternating satiety and starvation for 24 h. The weight, blood glucose level, and water intake of the rats were recorded. The Morris water maze (MWM) test was carried out to appraise the cognitive function at the end of week 12. Moreover, the morphological structure of hippocampal neurons was viewed through HE and Nissl staining, and transmission electron microscopy (TEM) was performed for ultrastructure observation. The protein expression levels of Nrf2, HO-1, NQO-1, Bax, Bcl-2, and Caspase-3 in the hippocampal tissues of rats were measured via Western blotting, and the mRNA expressions of Nrf2, HO-1, and NQO-1 were examined using qRT-PCR. Finally, Western blotting and immunohistochemistry were conducted to detect BDNF levels. Results. It was manifested that GF not only aggravated the impairment of spatial memory in rats with STZ-induced type 2 DM but also stimulated the loss, shrinkage, and apoptosis of hippocampal neurons. Regarding the expressions in murine hippocampal tissues, GF depressed Nrf2, HO-1, NQO-1, Bcl-2, and BDNF but boosted Caspase-3 and Bax. Conclusions. GF aggravates cognitive impairment by inhibiting the Nrf2 signaling pathway and inducing oxidative stress and apoptosis in the hippocampal tissues.

Background: Diabetic liver disease is one of the main complications that leads to the aggravation of diabetes, but it has not received sufficient attention. This study aimed to provide a better understanding of the altered molecular networks in in diabetic rats with liver damage after stem cell therapy. To a certain extent, our research would be instructive, since almost no studies of this kind have been performed on patients with diabetic liver disease after stem cell therapy. Methods: Streptozotocin-induced diabetic rats were treated with adipose-derived stem cells. RNA-Seq analysis was performed on the liver tissues of these animals, and key pathway factors were further identified and validated. Results: RNA-Seq analysis revealed numerous affected signaling pathways and functional categories. The results showed that the network of dual specificity phosphatase 1 (DUSP1), an oxidative stress-related gene, was prominently activated in the liver after stem cell therapy, and the enrichment of genes associated with liver damage, steatosis and fibrosis was also detected. The extracellular regulated protein kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may be involved in this process by regulating the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Conclusions: These data provide novel insights into liver biology, suggest common alterations in the molecular networks during diabetic liver damage, and show the advantages of stem cell therapy, indicating its further application potential for early treatment of diabetic liver damage and delaying the progression of liver fibrosis in the later stage.

ObjectiveTo evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis.MethodsPubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures.ResultsA total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 (CI: 2.18-4.10, I2 = 42.7%, P

Objective: The objective of this systematic review and meta-analysis is to assess the effectiveness and security of Chinese herbal medicine (CHM) in the therapy of painful diabetic neuropathy (PDN).Methods: We searched databases for randomized controlled trials (RCTs) of CHM in the treatment of PDN. Outcome indicators included nerve conduction velocity, clinical efficiency, pain score, TCM syndrome score, and adverse events. Stata 16.0 was used to carry out the Meta-analysis.Results: A total of 21 RCTs with 1,737 participants were included. This meta-analysis found that using CHM as adjuvant treatment or as monotherapy for PDN can improve SCV of median nerve [mean difference (MD) = 3.56, 95% Confidence interval (CI) (2.19, 4.92) ], MCV of median nerve [ MD = 3.82, 95% CI (2.51, 5.12) ], SCV of common peroneal nerve [ MD = 4.16, 95% CI (1.62, 6.70) ], MCV of common peroneal nerve [ MD = 4.37, 95% CI (1.82, 6.93) ], SCV of gastrocnemius nerve [ MD = 4.95, 95% CI (3.52, 6.37) ], SCV of tibial nerve [ MD = 3.17, 95% CI (−2.64, 8.99) ], MCV of tibial nerve [MD = 6.30, 95%CI (5.00, 7.60)] and clinical effective rate [ odds ratio (OR) = 4.00, 95% CI (2.89, 5.52) ] and reduce pain score [standardized mean difference (SMD) = -2.23, 95% CI (-3.04, -1.41) ], TCM syndrome score [ MD = -4.70, 95% CI (-6.61, -2.80) ]. In addition, compared to the control group, adverse events of Chinese medicine intervention occurred less.Conclusion: CHM as adjuvant therapy or single treatment has a good curative effect and is safe for patients with PDN, which is worthy of clinical promotion and use, however; higher quality clinical studies are still needed to prove.Systematic Review Registration:https://www.crd.york.ac.uk/, identifier CRD42022327967

Background Cognitive decline is one of the most widespread chronic complications of diabetes, which occurs in more than half of the patients with type 2 diabetes (T2DM). Emerging evidences have suggested that glucose variability (GV) is associated with the pathogenesis of diabetic complications. However, the influence of acute GV on cognitive dysfunction in T2DM is still controversial. The aim of the study was to evaluate the association between acute GV and cognitive defect in T2DM, and provide a most recent and comprehensive summary of the evidences in this research field. Methods PubMed, Cochrane library, EMBASE, Web of science, Sinomed, China National Knowledge Infrastructure (CNKI), and Wanfang were searched for articles that reported on the association between acute GV and cognitive impairment in T2DM. Results 9 eligible studies were included, with a total of 1263 patients with T2DM involved. Results showed that summary Fisher’s z value was -0.23 [95%CI (-0.39, -0.06)], suggesting statistical significance (P = 0.006). Summary r value was -0.22 [95%CI (-0.37, -0.06)]. A lower cognitive performance was found in the subjects with greater glucose variation, which has statistical significance. Mean amplitude of glycemic excursions (MAGE) was associated with a higher risk of poor functional outcomes. Fisher’s z value was -0.35 [95%CI (-0.43, -0.25)], indicating statistical significance (P = 0.011). Sensitivity analyses by omitting individual studies showed stability of the results. Conclusions Overall, higher acute GV is associated with an increased risk of cognitive impairment in patients with T2DM. Further studies should be required to determine whether targeted intervention of reducing acute GV could prevent cognitive decline.

With the rapid aging of the population, the control of age-related disease susceptibility and prognosis faces greater challenges. There is an urgent need for a strategy to maintain the vitality of elderly people. In this study, the effect of Renshen Guben (RSGB) oral liquid was investigated on an accelerated aging mice model of thyrotoxicosis by conventional detection methods combined with multiomics technology. The results showed that RSGB increased the number of neutrophils and lymphocytes, enhanced the function of lymphocytes, and increased the levels of complement and antimicrobial peptides, which indicated that RSGB improved the immunity of thyrotoxicosis mice at the cellular and molecular levels. RSGB corrected malnutrition in thyrotoxicosis mice by improving anemia, hypoalbuminemia, ion transporters, and vitamin-binding proteins. RSGB significantly reduced the lipotoxicity by reducing the level of fatty acids, triglyceride, sphingolipids, and glucocorticoids, thus increasing the level of docosapentaenoic acid (DPA) and bile acids, which contributed to improve immunosenescence. The intestinal defense ability of thyrotoxicosis mice was enhanced with the increase of bile acids and lactic acid bacteria by the RSGB treatment. The plant metabolomics analysis showed that there were various active components in RSGB oral liquid and medicated serum, including terpenoids, phenolic acids, flavonoids, tannin, alkaloids, organic acids, phenolamines, amino acids, and others. They have antioxidant, immune regulation, and anti-aging effects, which was the material basis of RSGB. Totally, RSGB protected the thyrotoxicosis mice against aging by improving immunosenescence, hypoproteinemia, lipotoxicity, and the intestinal flora. It will be beneficial for improving the disease susceptibility and prognosis of the elderly.

The problem of aging is mainly the increase of age-related diseases, and elderly patients have longer hospitalization and worse prognosis. Poorer nutritional status and immunosenescence may be predisposing and severe factors. The mechanism of the high incidence of diseases and poor prognosis behind aging is complex. Finding suitable aging models is of great significance to find strategies to prevent aging related events. In this study, the relationship between thyrotoxicosis and aging was investigated in mice. The results of routine blood tests and flow cytometry showed that immunosenescence occurred in thyrotoxicosis mice, which was characterized by a significant decrease in neutrophils, lymphocytes, CD4+/CD8+ and CD4+IFN-γ+ lymphocytes. Biochemical examination results showed that there were hypocholesterolemia, hypolipoproteinemia, and hyperlipidemia in thyrotoxicosis mice. Serum proteomics analysis showed that the downregulation of complement and coagulation proteins was another manifestation of declined immunity. Moreover, proteomics analysis showed that many downregulated proteins were related to homeostasis, mainly transport proteins. Their downregulation led to the disturbance of osmotic pressure, ion homeostasis, vitamin utilization, lipid transport, hyaluronic acid processing, and pH maintenance. Serum metabolomics analysis provided more detailed evidence of homeostasis disturbance, especially lipid metabolism disorder, including the downregulation of cholesterol, vitamin D, bile acids, docosanoids, and the upregulation of glucocorticoids, triglycerides, sphingolipids, and free fatty acids. The upregulated lipid metabolites were related to lipotoxicity, which might be one cause of immunosenescence and many aging related syndromes. This study provides evidence for the aging model of thyrotoxicosis mice, which can be used for exploring anti-aging drugs and strategies.

Aurora-A kinase, a serine/threonine mitotic kinase, is reportedly upregulated in skin tissues of individuals with type 2 diabetes mellitus , although its function in diabetes is unclear. C57BL/6 J mice were utilized to establish a type 2 diabetic model and explore the functions of Aurora-A in diabetes. Aurora-A was highly expressed in the pancreas of the diabetic mice as confirmed by western blot. Inhibition of Aurora-A did not affect fasting blood glucose and body weight, but did improve insulin resistance, as indicated by improved oral glucose tolerance, insulin tolerance, and the Homoeostasis Model Assessment-Insulin Resistance index. Blockade of Aurora-A dramatically decreased the number of infiltrating macrophages in the pancreas in parallel with decreases in the levels of serum insulin and interleukin-6 (IL-6) mRNA. The levels of phosphorylated forms of protein kinase B, which are the key mediators of in insulin resistance, were not induced in liver, adipocyte tissues, and skeletal muscle by alisertib treatment. Our findings indicate that suppression of Aurora-A could at least partially enhance insulin sensitivity by decreasing the number of infiltrating macrophages and IL-6 level in a type 2 diabetic mouse model.

Hyperspectral image (HSI) classification is a fundamental and challenging problem in remote sensing and its various applications. However, it is difficult to perfectly classify remotely sensed hyperspectral data by directly using classification techniques developed in pattern recognition. This is partially owing to a multitude of noise points and the limited training samples. Based on multinomial logistic regression (MLR), the local mean-based pseudo nearest neighbor (LMPNN) rule, and the discontinuity preserving relaxation (DPR) method, in this paper, a semi-supervised method for HSI classification is proposed. In pre-processing and post-processing, the DPR strategy is adopted to denoise the original hyperspectral data and improve the classification accuracy, respectively. The application of two classifiers, MLR and LMPNN, can automatically acquire more labeled samples in terms of a few labeled instances per class. This is termed the pre-classification procedure. The final classification result of the HSI is obtained by employing the MLRsub approach. The effectiveness of the proposal is experimentally evaluated by two real hyperspectral datasets, which are widely used to test the performance of the HSI classification algorithm. The comparison results using several competing methods confirm that the proposed method is effective, even for limited training samples.

The key problem for attribute reduction to information systems is how to evaluate the importance of an attribute. The algorithms are challenged by the variety of data forms in information system. Based on rough sets theory we present a new approach to attribute reduction for incomplete information systems and fuzzy valued information systems. In order to evaluate the importance of an attribute effectively, a novel algorithm with rigorous theorem is proposed. Experiments show the effect of proposed algorithm.