Development and validation of a new multiplex panel using SNaPshot-based DIP-TriSNP markers for forensic DNA mixtures.

Short tandem repeat analysis is challenging when dealing with unbalanced mixtures in forensic cases due to the presence of stutter peaks and large amplicons. In this research, we propose a novel genetic marker called DIP-TriSNP, which combines deletion/insertion polymorphism (DIP) with tri-allelic single nucleotide polymorphism in less than 230 bp length of human genome. Based on multiplex PCR and SNaPShot, a panel, including 14 autosomal DIP-TriSNPs and one Y chromosomal DIP-SNP, had been developed and applied to genotyping 102 unrelated Han Chinese individuals in Sichuan of China and simulated a mixture study. The panel sensitivity can reach as low as 0.1 ng DNA template, and the minor contributor of DNA can be detected with the highest ratio of 19:1, as indicated by the obtained results. In the Sichuan Han population, the cumulative probability of informative genotypes reached 0.997092, with a combined power of discrimination of 0.999999998801. The panel was estimated to detect more than two alleles in at least one locus in 99.69% of mixtures of the Sichuan Han population. In conclusion, DIP-TriSNPs have shown promising as an innovative DNA marker for identifying the minor contributor in unbalanced DNA mixtures, offering advantages such as short amplifications, increased polymorphism, and heightened sensitivity.

Current Status and Future Direction of Albumin-Bilirubin in Hepatocellular Carcinoma: A Bibliometric Analysis.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common malignant tumor, so we need a convenient and objective way to diagnose and treat HCC. We discuss the current situation, progress, hotspots, and existing problems of Albumin-Bilirubin (ALBI) in HCC, which can provide new ideas for the prevention, diagnosis, and treatment of HCC. METHODS: We adopt Excel 2019 software and visual analysis tools based on Web of Science database search. This manuscript uses VOSviewer, Co-Occurrence13.3 (COOC13.3) software to conduct overall trend analysis, synonym merging, frequency of countries, journals, institutions, funds, dissimilarity matrices, co-occurrence matrices, bimodal matrices, coupling matrices, cluster analysis of topic evolution time zone graphs. RESULTS: A total of 610 papers were included, and the number of papers output showed an overall upward trend. ALBI has been valued by the industry in HCC and plays an important role in diagnosing and treating HCC, even better than the classic Child-Pugh (C-P) grade. At the same time, hot spots in the treatment of HCC and other applications of ALBI were discovered. CONCLUSION: ALBI score is a convenient and objective liver function evaluation index, which plays an important role in the prediction of patient survival rate and prognosis. Promoting the ALBI score in HCC can help doctors judge the patient's condition and improve the diagnosis and precise treatment effect.

ADAR1 prevents ZBP1-dependent PANoptosis via A-to-I RNA editing in developmental sevoflurane neurotoxicity.

It is well established that sevoflurane exposure leads to widespread neuronal cell death in the developing brain. Adenosine deaminase acting on RNA-1 (ADAR1) dependent adenosine-to-inosine (A-to-I) RNA editing is dynamically regulated throughout brain development. The current investigation is designed to interrogate the contributed role of ADAR1 in developmental sevoflurane neurotoxicity. Herein, we provide evidence to show that developmental sevoflurane priming triggers neuronal pyroptosis, apoptosis and necroptosis (PANoptosis), and elicits the release of inflammatory factors including IL-1ß, IL-18, TNF-α and IFN-γ. Additionally, ADAR1-P150, but not ADAR1-P110, depresses cellular PANoptosis and inflammatory response by competing with Z-DNA/RNA binding protein 1 (ZBP1) for binding to Z-RNA in the presence of sevoflurane. Further investigation demonstrates that ADAR1-dependent A-to-I RNA editing mitigates developmental sevoflurane-induced neuronal PANoptosis. To restore RNA editing, we utilize adeno-associated virus (AAV) to deliver engineered circular ADAR-recruiting guide RNAs (cadRNAs) into cells, which is capable of recruiting endogenous adenosine deaminases to promote cellular A-to-I RNA editing. As anticipated, AAV-cadRNAs diminishes sevoflurane-induced cellular Z-RNA production and PANoptosis, which could be abolished by ADAR1-P150 shRNA transfection. Moreover, AAV-cadRNAs delivery ameliorates developmental sevoflurane-induced spatial and emotional cognitive deficits without influence on locomotor activity. Taken together, these results illustrate that ADAR1-P150 exhibits a prominent role in preventing ZBP1-dependent PANoptosis through A-to-I RNA editing in developmental sevoflurane neurotoxicity. Application of engineered cadRNAs to rectify the compromised ADAR1-dependent A-to-I RNA editing provides an inspiring direction for possible clinical preventions and therapeutics.

Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1ß) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.

Safety and efficacy of laser trabeculoplasty compared to drug therapy for the management of open-angle glaucoma: systematic review and meta-analysis study.

BACKGROUND: Intraocular  pressure (IOP) reduction is the approach that is commonly accepted for the control of open-angle glaucoma (OAG). Medical therapy is typically the first-line of treatment. Laser trabeculoplasty (LT) is an alternative therapy; however, whether pharmaco-therapeutic options can be replaced by LT as the first-line is still debatable. METHODS: studies conducted till July 2023 that compared the efficacy of medications and LT for OAG were retrieved from databases such as Embase, PubMed, Cochrane Library, and Web of Science. We completed data extraction for outcomes of interest. The quality of eligible studies was evaluated and random-effects (RE) model was applied for analysis. RESULTS: A total of eighteen trials with 2024 patients were included in the analysis. Overall, there was no statistically significant difference between therapies including laser trabeculoplasty (LT) and drug therapy in terms of successful IOP control (RR:1.30, 95%CI: 0.96, 1.78, P = 0.09, I2 = 96%), and reducing intraocular pressure (IOP) (MD:0.15; 95%CI:-0.55,0.85; P = 0.67, I2 = 62%). A significant reduction in drug therapy need in comparison to the group that received medicine (MD:-1.07; 95%CI;-1.21,-0.93), P < 0.001, with a low heterogeneity level (I2 = 16%). Adverse ocular events were more common in the argon laser group (RR:11.71, 95%CI: 9.93, 23.1; P < 0.001). CONCLUSION: Both LT and topical drug therapy exhibit comparable rates of success and efficacy in reducing intraocular pressure in patients with open-angle glaucoma. Selective LT is considered a safe treatment option with a reduced occurrence of adverse effects on the eyes while eliminating the possible adherence concerns associated with topical medicine and it can be considered a viable initial option for first OAG treatment. KEY MESSAGES: What is known Drug therapy is typically the 1st line of treatment for open-angle glaucoma. Although drugs have been shown to effectively reduce intraocular pressure (IOP), they are associated with a range of ocular and systemic negative effects which contributes to suboptimal adherence to medications. Laser trabeculoplasty (LT) is an alternative therapy; however, whether pharmaco-therapeutic options can be replaced by LT as the first-line is still debatable. What is new In terms of IOP reduction and IOP success rate, LT therapy was comparable in efficacy to drug therapy according to our findings. The safety profile of selective LT was found to be preferable compared to Argon LT.

Development of a self-assessment tool to evaluate the readiness of pharmacy departments for internship training in China: a two-phase study.

OBJECTIVES: Internships in the pharmacy departments of training hospitals represent a crucial stage in the professional development of pharmacy students. However, the quality of internship training varies significantly across training hospitals in China, and there is a lack of standardized readiness evaluation tools. Therefore, the purpose of this study was to develop a self-assessment tool to evaluate the preparedness of training hospitals for providing internship training. METHODS: This study employed an exploratory mixed-methods approach and was conducted in two phases. In the first phase, during 2021, focus groups were conducted with 16 interns from three tertiary hospitals in Henan Province. In 2022, 14 preceptors from tertiary hospitals in various provinces were interviewed either one-on-one or in focus groups. The interview data were analyzed using thematic analysis to compile a set of self-assessment indicators for internship training readiness. Subsequently, the initial draft of the self-assessment tool for internship training readiness was developed by integrating the indicators derived from the interviews and literature review. In the second phase, the Delphi method was utilized. In 2023, the experts participated in two rounds of correspondence (21 experts in the first round and 19 in the second round), and consensus was reached on the indicators of the self-assessment tool after the two rounds. Meanwhile, these experts assessed the current status of internship training in training hospitals across China. RESULTS: The qualitative findings of the first phase included five themes and 22 sub-themes, which were integrated with the indicators derived from the literature review to develop an initial indicator framework for the second phase. This initial framework comprised five domains and 37 items. The second phase involved two rounds of expert surveys, with effective response rates of 90.48% and 89.47%, respectively. Ultimately, the self-assessment tool for evaluating the readiness of pharmacy departments in training hospitals for internships included five dimensions and 35 secondary indicators: (1) organizational structure, (2) training content, (3) training mode, (4) effectiveness evaluation, and (5) emergency management. Additionally, experts assessed the readiness of pharmacy departments in Chinese training hospitals for internships, yielding varied results. Emergency management preparedness scored the highest, followed by organizational structure and training content preparation. However, the modes of internship training and the evaluation of training effectiveness received lower scores. CONCLUSION: The developed tool provides a comprehensive self-assessment checklist for the pharmacy departments of training hospitals and possesses the potential to enhance the development of more effective internship training programs.

Decoding the possible mechanism of action of Paeoniflorigenone in combating Aflatoxin B1-induced liver cancer: an investigation using network pharmacology and bioinformatics analysis.

Moutan cortex has demonstrated antitumor properties attributed to its bioactive compound Paeoniflorigenone (PA). Nevertheless, there is limited research on the efficacy of PA in the prevention and treatment of hepatocellular carcinoma (HCC). We aimed to investigate the potential pharmacological mechanisms of PA in the treatment of Aflatoxin B1 (AFB1)-induced hepatocarcinogenesis using network pharmacology and bioinformatics analysis approaches. Through various databases and bioinformatics analysis approaches, 34 shared targets were identified as potential candidate genes for PA in fighting liver cancer caused by AFB1. Pathway analysis revealed involvement in cell cycle, HIF-1, and Rap1 pathways. A risk assessment model was developed using LASSO regression, showing an association between the identified genes and the tumor immune microenvironment. The genes within the risk model were found to be linked to the immune response in liver cancer. Molecular docking studies indicated that PA interacts with its targets through hydrogen bonding and hydrophobic interactions. This study provides insights into the possible mechanisms of PA in liver cancer treatment and offers a predictive model for assessing the risk level of individuals with liver cancer. These findings have significant implications for the therapeutic strategies in managing liver cancer patients.

A Bibliometric and Visual Analysis of the Current Status and Trends of Forensic Mixed Stain Research.

OBJECTIVES: To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach. METHODS: The literature of forensic mixed stain included in the core collection of Web of Science database from 2011 to 2022 were collected as the study object, and the annual publication number, countrie (region), institution, journal, keywords, etc. were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software. RESULTS: A total of 732 articles on forensic mixed stain were included from 2011 to 2022, with the annual number of articles published and the annual citation frequency showing a steady increase year by year. Among the 59 countries (regions) with the most published articles, the United States ranked first with 246 articles, followed by China with 153 articles. The literature came from 104 journals, and the total number of articles published in the top 10 journals was 633. FORENSIC SCI INT GENET ranked first with 307 articles. Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters, namely the genetic marker development group (blue), the mixed stain typing analysis theory group (red), the sequencing analysis group (yellow), and the case sample research group (green). It can be divided into four development stages in terms of different time periods: early development (2011-2013), middle development (2014-2016), rapid development (2017-2020) and latest development (2021-2022). CONCLUSIONS: The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend. Machine learning, next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years, which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

The Integration of Nanomedicine with Traditional Chinese Medicine: Drug Delivery of Natural Products and Other Opportunities.

The integration of progressive technologies such as nanomedicine with the use of natural products from traditional medicine (TM) provides a unique opportunity for the longed-for harmonization between traditional and modern medicine. Although several actions have been initiated decades ago, a disparity of reasons including some misunderstandings between each other limits the possibilities of a truly complementation. Herein, we analyze some common challenges between nanomedicine and traditional Chinese medicine (TCM). These challenges, if solved in a consensual way, can give a boost to such harmonization. Nanomedicine is a recently born technology, while TCM has been used by the Chinese people for thousands of years. However, for these disciplines, the regulation and standardization of many of the protocols, especially related to the toxicity and safety, regulatory aspects, and manufacturing procedures, are under discussion. Besides, both TCM and nanomedicine still need to achieve a wider social acceptance. Herein, we first briefly discuss the strengths and weaknesses of TCM. This analysis serves to focus afterward on the aspects where TCM and nanomedicine can mutually help to bridge the existing gaps between TCM and Western modern medicine. As discussed, many of these challenges can be applied to TM in general. Finally, recent successful cases in scientific literature that merge TCM and nanomedicine are reviewed as examples of the benefits of this harmonization.

Effects of exergaming on cognitive functions and loneliness of older adults with cognitive frailty.

OBJECTIVES: Cognitive frailty combines physical frailty and cognitive impairment in the absence of dementia. The prompt detection of cognitive frailty and early implementation of preventive interventions may reduce the incidence of dementia. However, intervention studies of exergaming in older adults with cognitive frailty are scant. Therefore, we aim to investigate the effectiveness of exergaming on cognitive functions and loneliness among older adults with cognitive frailty. DESIGN: Quasi-experimental design. METHODS: Participants were recruited from four community settings. The experimental group participated in two 40-min group exergaming sessions weekly for eight weeks; the control group received usual care. The outcome measures were the Montreal Cognitive Assessment (MoCA) and the Chinese Version of the Loneliness Scale. Analyses of covariance were conducted to analyze whether exergaming influenced participants' cognitive functions and loneliness. In addition, the effect size of the posttest of the experimental group relative to its baseline value was calculated to determine the effectiveness of the intervention. RESULT: 69 older adults with cognitive frailty were included, and 35 and 34 were assigned to the experimental and control groups, respectively. The exergaming effectively improved the cognitive function of older adults with cognitive frailty. CONCLUSIONS: Exergaming interventions can effectively improve the cognitive functions of older adults with cognitive frailty but do not positively affect loneliness. We provide evidence to healthcare workers to apply exergaming interventions for older adults with cognitive frailty to improve cognitive function.

A comparison of treatment between mini T-plate and headless cannulated compression screw in calcaneal osteotomy.

PURPOSE: In clinical studies, we discovered that when using headless cannulated compression screw fixation, many patients complain of heel pain and frequently need to have the screws removed, whereas this occurrence is uncommon with plate fixation. This study aims to compare the clinical outcome of a mini T-plate and headless cannulated compression screws in calcaneal osteotomy. METHODS: We reviewed the medical records of patients who had calcaneal osteotomy performed by one senior chief surgeon in our hospital between January 2014 and May 2021. Thirty-nine patients met the selection criteria: 22 were fixed using a mini T-plate through a modified small "L" incision on the lateral aspect of the calcaneus and 17 were fixed using double screws through an oblique incision on the lateral aspect of the calcaneus. Then, we compared the patient demographics, surgical statistics, and postoperative complications in calcaneal osteotomy between a mini T-plate and double 6.5-mm headless cannulated compressed screws. RESULTS: Each patient attained radiographic union. The average age was 49.23±13.80 (range: 24-76) years and the average follow-up duration was 47.07±8.64 (range: 36-66) weeks. The average operation duration and times of intraoperative fluoroscopy were significantly lower in the mini T-plate group (P<0.05). There was a savings of $838.88 per patient when using double screws for fixation. The incidence of hardware-related pain and implant removal was lower in the mini T-plate group (P<0.05). There is no significant difference between the two groups in terms of delayed incision healing and clinical neurological complications (P>0.05). CONCLUSIONS: In calcaneal osteotomy, the operation duration, times of intraoperative fluoroscopy, hardware-related pain, and implant removal rate were lower with mini T-plate fixation than with double screws fixation. Therefore, we consider that the mini T-plate would be a good alternative to double screws in calcaneal osteotomy.

Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy.

Herbal medicines have gained recognition among physicians and patients due to their lower adverse effects compared to modern medicines. They are extensively used to treat various diseases, including cancer, cardiovascular issues, chronic inflammation, microbial contamination, diabetes, obesity, and hepatic disorders, among others. Unfortunately, the clinical application of herbal medicines is limited by their low solubility and inadequate bioavailability. Utilizing herbal medicines in the form of nanocrystals (herbal medicine nanocrystals) has shown potential in enhancing solubility and bioavailability by reducing the particle size, increasing the specific surface area, and modifying the absorption mechanisms. Multiple studies have demonstrated that these nanocrystals significantly improve drug efficacy by reducing toxicity and increasing bioavailability. This review comprehensively examines therapeutic approaches based on herbal medicine nanocrystals. It covers the preparation principles, key factors influencing nucleation and polymorphism control, applications, and limitations. The review underscores the importance of optimizing delivery systems for successful herbal medicine nanocrystal therapeutics. Furthermore, it discusses the main challenges and opportunities in developing herbal medicine nanocrystals for the purpose of treating conditions such as cancer, inflammatory diseases, cardiovascular disorders, mental and nervous diseases, and antimicrobial infections. In conclusion, we have deliberated regarding the hurdles and forthcoming outlook in the realm of nanotoxicity, in vivo kinetics, herbal ingredients as stabilizers of nanocrystals, and the potential for surmounting drug resistance through the utilization of nanocrystalline formulations in herbal medicine. We anticipate that this review will offer innovative insights into the development of herbal medicine nanocrystals as a promising and novel therapeutic strategy.

The Effective Treatment of Purpurin on Inflammation and Adjuvant-Induced Arthritis.

Rubia cordifolia L. (Rubiaceae), one of the traditional anti-rheumatic herbal medicines in China, has been used to treat rheumatoid arthritis (RA) since ancient times. Purpurin, an active compound of Rubia cordifolia L., has been identified in previous studies and exerts antibacterial, antigenotoxic, anticancer, and antioxidant effects. However, the efficacy and the underlying mechanism of purpurin to alleviate RA are unclear. In this study, the effect of purpurin on inflammation was investigated using macrophage RAW264.7 inflammatory cells, induced by lipopolysaccharide (LPS), and adjuvant-induced arthritis (AIA) rat was established to explore the effect of purpurin on joint damage and immune disorders; the network pharmacology and molecular docking were integrated to dig out the prospective target. Purpurin showed significantly anti-inflammatory effect by reducing the content of IL-6, TNF-α, and IL-1ß and increasing IL-10. Besides, purpurin obviously improved joint injury and hypotoxicity in the liver and spleen and regulated the level of FOXP3 and CD4+/CD8+. Furthermore, purpurin reduced the MMP3 content of AIA rats. Network pharmacology and molecular docking also suggested that MMP3 may be the key target of purpurin against RA. The results of this study strongly indicated that purpurin has a potential effect on anti-RA.

The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma.

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Analysis of Genetic Polymorphism and Population Genetic Structure of 57 Autosomal InDel Loci in Beichuan Qiang Population.

OBJECTIVES: To investigate the genetic information of 57 autosomal InDel loci (A-InDels) included in AGCU InDel 60 fluorescence detection kit in the Beichuan Qiang population of Sichuan Province and evaluate its application value in forensic medicine. METHODS: A total of 200 unrelated healthy individuals from Beichuan Qiang population of Sichuan Province were typing detected by AGCU InDel 60 fluorescence detection kit. Allele frequencies and population genetic parameters of the 57 A-InDels were statistically analyzed and compared with the available data of 26 populations. RESULTS: After Bonferroni correction, there was no linkage disequilibrium between the 57 A-InDels, and all loci were in Hardy-Weinberg equilibrium. Except for rs66595817 and rs72085595, the minor allele frequencies of 55 A-InDels were above 0.3. PIC ranged from 0.298 3 to 0.375 0, CDP was 1-2.974 8×10-24, CPEduo was 0.999 062 660, and CPEtrio was 0.999 999 999. The calculation of the genetic distance showed that Beichuan Qiang population had the closest genetic distances with Beijing Han and South China Han populations, but far away from African populations. CONCLUSIONS: The 57 A-InDels in AGCU InDel 60 fluorescence detection kit have a good genetic polymorphism in Beichuan Qiang population of Sichuan Province, which can be used as effective supplemental for individual identification and paternity identification in forensic medicine.

MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation.

BACKGROUND: Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma. METHODS: MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice. RESULTS: Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group. CONCLUSION: In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.

Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3ß. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3ß were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

Construction and evaluation of multidomain attention training to improve alertness attention, sustained attention, and visual-spatial attention in older adults with mild cognitive impairment: A randomized controlled trial.

OBJECTIVES: We aimed to analyze the effects of multidomain attention training on alertness, sustained attention, and visual-spatial attention in older adults with mild cognitive impairment (MCI). DESIGN: The design used in this study was a two-arm, parallel group, double-blind randomized controlled trial. SETTING AND PARTICIPANTS: The participants of the study were seventy-eight older adults with MCI (mean age: 79.5 ± 7.9 years) from retirement centers and community housing for the elderly. INTERVENTION: The participants were randomly assigned to an experimental group (multidomain attention training, n = 39) or an active control group (n = 39). Both groups underwent training sessions for 45 minutes three times per week for 6 weeks (18 sessions in total). MEASURES: The main efficacy indicator was alertness (Trail Making Test Part B), sustained attention (Digit Vigilance Test), and visual-spatial attention (Trail Making Test Part A). The secondary outcome indicators were other cognitive functions (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA] subscales). Measurements were obtained at pretest, posttest, and 3 and 6 months after training. RESULTS: The results were analyzed by a generalized estimating equation (GEE), which indicated that attention outcomes (alertness, sustained attention, and visual-spatial attention) of the experimental group did not improve after training. However, the experimental group displayed a significant improvement in the attention, memory, and orientation of MMSE and MoCA subscales over a period of 6 months and also showed superior results compared with the control group. CONCLUSIONS: Multidomain attention training demonstrated improved alertness and visual-spatial attention for posttest after 6 months. We also outline potential future advances in attention training for improving attention in older adults with MCI.

The Construction and Evaluation of Executive Attention Training to Improve Selective Attention, Focused Attention, and Divided Attention for Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVES: To examine the immediate and long-term effects of executive attention training on selective attention, focused attention, and divided attention in older adults with mild cognitive impairment. METHODS: A double-blind, multisite randomized controlled trial at five sites. Seventy participants (mean age: 78.19 ± 7.22 years) were assigned to an experimental group (executive attention training, n = 35) or an active control group (n = 35). The training duration was the same for both groups (45 minutes per session, 3 times per week, 18 sessions in total). Primary outcome measure was selective attention (Digit Span Task). Secondary outcome measures included focused attention (Stroop Color Word Test) and divided attention (Trail-Making Test Part B). Data were collected at pretest, post-test, 3-month follow-up, and 6-month follow-up. RESULTS: In GEE analysis, findings indicated a significant improvement in selective attention at post-test, whereas divided attention showed significant reducing omission error at 3-month follow-up. There was no significant effect of group in focused attention associated with the executive attention training compared with active control group. CONCLUSION: The executive attention training significantly improved selective attention and divided attention performance. Future studies should identify transfer effects of attention training, and that can employ early screening to provide integrated attention training, and decrease its relevant risks on competency in performing daily activities, such as falling and driving.

Development and effectiveness of virtual interactive working memory training for older people with mild cognitive impairment: a single-blind randomised controlled trial.

BACKGROUND: memory training is a potential intervention for retaining memory and reducing dementia risk in older adults with mild cognitive impairment (MCI). OBJECTIVE: this study examined the effect of virtual interactive working memory training (VIMT) in older adults with MCI. DESIGN: single-blind, two-arm parallel-group, randomised controlled design. SETTING: retirement homes, institutions, and communities. SUBJECTS: a total of 66 older adults with MCI were recruited (mean age: 78.5 ± 7.6 years). METHODS: participants were randomly assigned to the experimental group (VIMT, n = 33) or active control group (n = 33). The VIMT program used the CogniPlus (includes four training modules). Both groups attended 45 min sessions 3 times per week, a total of 36 sessions. The primary outcome was working memory; secondary outcomes were immediate memory, delayed memory, subjective memory complaints and global cognitive function. All variables were measured at pre-test, post-test, and 3-month follow-up. RESULTS: between group, the effect of working memory adjusted mean difference by 1.75 (95% CI: 0.56 to 2.94; P < 0.01) at post-test. The results were analysed by a generalised estimating equation, which indicated that VIMT group significantly improved working memory at post-test (P = 0.01) relative to the active control group. CONCLUSIONS: the applied VIMT program can enable older adults with MCI to maintain their working memory and reduce the rate of cognitive deterioration. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov (no.: NCT02462135).