Hydrogel based on M1 macrophage lysate and alginate loading with oxaliplatin for effective immunomodulation to inhibit melanoma progression, recurrence and metastasis.

Despite the monumental success of immunotherapy in treating melanoma clinically, it still confronts significant challenges, chiefly that singular immunomodulatory tactics are insufficient to suppress the recurrence and metastasis of melanoma. Herein, these challenges are addressed by a hydrogel based on M1 macrophage lysate and alginate (M1LMHA) loaded with oxaliplatin (OXA), named M1LMHA@OXA.The results obtained from scanning electron microscopy and confocal microscopy indicate that the structure and morphology of M1LMHA@OXA remain unchanged. Flow cytometry results reveal that M1LMHA@OXA significantly promotes the maturation of dendritic cells (DCs) and enhances the proliferation of T lymphocytes. In a subcutaneous melanoma transplant model, M1LMHA@OXA effectively suppressed tumor growth in comparison to OXA alone and M1LMHA alone. Flow cytometry demonstrated that M1LMHA@OXA markedly increased the number of mature DCs and CD8+ T cells at the tumor site, while significantly reducing the quantity of M2-like tumor-associated macrophages (TAM) and enhancing the presence of M1 macrophages. Enzyme-linked immunosorbent assay (ELISA) results indicated that following treatment with M1LMHA@OXA, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the bloodstream of mice were significantly elevated, whereas interleukin-10 (IL-10) exhibited no significant difference. This outcome further corroborates the ability of M1LMHA@OXA to substantially bolster the immune capability of mice. Similar results have also been observed in a melanoma subcutaneous transplantation recurrence model, and optical imaging of the lungs of mice revealed that M1LMHA@OXA inhibited tumor metastasis to the lungs. Notably, M1LMHA@OXA exhibits an exceptional therapeutic effect on the growth, post-surgical recurrence, and metastasis of the B16F10 melanoma. Therefore, this study provides a straightforward strategy that leverages the cooperative regulation of multiple immune cells to thwart the proliferation, recurrence, and spread of melanoma.

SIX4 Activation in Inflammatory Response Drives the Transformation of Colorectal Epithelium into Inflammation and Tumor via Feedback-Enhancing Inflammatory Signaling to Induce Tumor Stemness Signaling.

Some colorectal cancer patients have experienced normal epithelial transformation into inflammatory and tumor states, but the molecular basis still needs to be further determined. The expression levels of SIX4 are gradually increased in dextran sodium sulfate (DSS) and azoxymethane (AOM)/DSS-induced colonic epithelial inflammation and tumors, respectively, in mice. Targeting SIX4 alleviates intestinal inflammation occurrence and reduces adenoma formation in mice. Clinical sample assays indicated that SIX4 is upregulated in inflammatory bowel disease (IBD) and colorectal cancer (CRC) tissues compared to normal colorectal tissues. In a subsequent study, we found that SIX4, transcriptionally activated by the proinflammatory IL-6/STAT3 signal, binds to c-Jun to transcribe IL-6, thus forming a positive IL-6/STAT3/SIX4/c-Jun feedback loop, which further induces intestinal inflammation occurrence. In addition, elevated SIX4 also induces the expression of DeltaNp63, rather than wild-type p63, by binding to its promoter and thus facilitates the activation of tumor stemness signals, which ultimately leads to the formation of colorectal cancer. Our study first observes that activated SIX4 in inflammation induction drives the transformation of colorectal epithelium into inflammation and tumor, which demonstrates SIX4 as a significant therapeutic target in IBD and colitis-associated colorectal cancer (CAC) and CRC pathogenesis.

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.

SAP130 mediates crosstalk between hepatocyte ferroptosis and M1 macrophage polarization in PFOS-induced hepatotoxicity.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant widely utilized in industrial manufacturing and daily life, leading to significant environmental accumulation and various public health issues. This study aims to characterize spliceosome-associated protein 130 (SAP130) as a key mediator of crosstalk between hepatocytes and macrophages, elucidating its role in PFOS-induced liver inflammation. The data demonstrate that PFOS exposure induces ferroptosis in mouse liver and AML12 cells. During ferroptosis, SAP130 is released from injured hepatocytes into the microenvironment, binding to macrophage-inducible C-type lectin (Mincle) and activating the Mincle/Syk signaling pathway in macrophages, ultimately promoting M1 polarization and exacerbating liver injury. Treatment with the ferroptosis inhibitor Ferrostatin-1 reduces SAP130 release, inhibits Mincle/Syk signaling activation, and mitigates inflammatory response. Furthermore, siSAP130 suppresses the activation of the Mincle signaling pathway and M1 polarization in BMDM cells. Conversely, treatment with the ferroptosis agonist Erastin enhances paracrine secretion of SAP130 and exacerbates inflammation. These findings emphasize the significance of hepatocyte-macrophage crosstalk as a critical pathway for PFOS-induced liver injury in mice while highlighting SAP130 as a pivotal regulator of ferroptosis and inflammation, thereby elucidating the potential mechanism of PFOS-induced liver injury.

Efficacy comparison of multipoint and single point scanning panretinal laser photocoagulation in non-proliferative diabetic retinopathy treatment.

BACKGROUND: Non-proliferative diabetic retinopathy (NPDR) poses a significant challenge in diabetes management due to its microvascular changes in the retina. Laser photocoagulation, a conventional therapy, aims to mitigate the risk of progressing to proliferative diabetic retinopathy (PDR). AIM: To compare the efficacy and safety of multi-spot vs single-spot scanning panretinal laser photocoagulation in NPDR patients. METHODS: Forty-nine NPDR patients (86 eyes) treated between September 2020 and July 2022 were included. They were randomly allocated into single-spot (n = 23, 40 eyes) and multi-spot (n = 26, 46 eyes) groups. Treatment outcomes, including best-corrected visual acuity (BCVA), central macular thickness (CMT), and mean threshold sensitivity, were assessed at predetermined intervals over 12 months. Adverse reactions were also recorded. RESULTS: Energy levels did not significantly differ between groups (P > 0.05), but the multi-spot group exhibited lower energy density (P < 0.05). BCVA and CMT improvements were noted in the multi-spot group at one-month post-treatment (P < 0.05). Adverse reaction incidence was similar between groups (P > 0.05). CONCLUSION: While energy intensity and safety were comparable between modalities, multi-spot scanning demonstrated lower energy density and showed superior short-term improvements in BCVA and CMT for NPDR patients, with reduced laser-induced damage.

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.

Single-cell RNA sequencing reveals special basal cells and fibroblasts in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most predominant type of idiopathic interstitial pneumonia and has an increasing incidence, poor prognosis, and unclear pathogenesis. In order to investigate the molecular mechanisms underlying IPF further, we performed single-cell RNA sequencing analysis on three healthy controls and five IPF lung tissue samples. The results revealed a significant shift in epithelial cells (ECs) phenotypes in IPF, which may be attributed to the differentiation of alveolar type 2 cells to basal cells. In addition, several previously unrecognized basal cell subtypes were preliminarily identified, including extracellular matrix basal cells, which were increased in the IPF group. We identified a special population of fibroblasts that highly expressed extracellular matrix-related genes, POSTN, CTHRC1, COL3A1, COL5A2, and COL12A1. We propose that the close interaction between ECs and fibroblasts through ligand-receptor pairs may have a critical function in IPF development. Collectively, these outcomes provide innovative perspectives on the complexity and diversity of basal cells and fibroblasts in IPF and contribute to the understanding of possible mechanisms in pathological lung fibrosis.

C-phycocyanin reinforces autophagy to block pulmonary fibrogenesis by inhibiting lncIAPF biogenesis.

Pulmonary fibrosis is a chronic and irreversible progressive lung disease caused by various factors, such as age and environmental pollution. With countries stepping into an aging society and the seriousness of environmental pollution caused by global industrialization, the incidence of pulmonary fibrosis is annually increasing. However, no effective drug is available for pulmonary fibrosis treatment. C-phycocyanin (C-PC), extracted from blue-green algae, has good water solubility and antioxidation. This study elucidated that C-PC reinforces autophagy to block pulmonary fibrogenesis by inhibiting long noncoding RNA (lncRNA) biogenesis in vivo and in vitro. Cleavage under targets and release using nuclease (CUT & RUN)-PCR, co-immunoprecipitation (Co-IP), and nuclear-cytoplasmic separation experiments clarified that C-PC blocked the nuclear translocation of activating transcription factor 3 (ATF3) to prevent the binding between ATF3 and transcription factor Smad3, thereby hindering lncIAPF transcription. Human antigen R (HuR) truncation experiment and RNA binding protein immunoprecipitation (RIP) were then performed to identify the binding domain with lncIAPF in the 244-322 aa of HuR. lncIAPF exerted its profibrogenic function through the binding protein HuR, a negative regulator of autophagy. In summary, C-PC promoted autophagy via down-regulating the lncIAPF-HuR-mediated signal pathway to alleviate pulmonary fibrosis, showing its potential as a drug for treating pulmonary fibrosis. Exploring how C-PC interacts with biological molecules will help us understand the mechanism of this drug and provide valuable target genes to design new drugs.

A cross-linked macropore hydrogel based on M1 macrophage lysate and alginate regulates tumor-associated macrophages for the treatment of melanoma.

Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy.

Causal associations of antioxidants with Alzheimer's disease and cognitive function: a Mendelian randomisation study.

BACKGROUND: Circulating antioxidants are associated with a lower risk of Alzheimer's disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR). METHODS: Single nucleotide polymorphisms strongly (p<5×10-8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, ß-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis. RESULTS: Higher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (ß=-0.026, 95% CI -0.044 to -0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses. CONCLUSION: Our results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.

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.

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.

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.

Antidepressant effects of dexmedetomidine compared with ECT in patients with treatment-resistant depression.

OBJECTIVE: This pilot study was designed to investigate the antidepressant effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, in patients with treatment-resistant depression (TRD). The antidepressant effects of dexmedetomidine was compared with ECT, which is widely used in clinical practice for treatment of patients with TRD. METHODS: Seventy six patients with TRD were randomly assigned to receive 10 sessions of DEX infusions or electroconvulsive therapy (ECT) treatment. The primary outcome was the changes of depression severity determined by the improvement of 24-item Hamilton Depression Rating Scale (HDRS-24). The second outcomes were the rates of therapeutic response (reduction in HDRS-24 ≥ 50 %) and remission (HDRS-24 ≤ 10 and reduction in HDRS-24 ≥ 60 %) at posttreatment and after 3 months of follow-up visits. RESULTS: We found that 10 sessions of DEX infusions or ECT treatments significantly improved HDRS-24 scores at posttreatment and after 3 months of follow-up visits compared with the baseline. In addition, there was no significant difference between DEX infusions and ECT treatments regarding HDRS-24 at these evaluating points. Furthermore, the depression severity dropped to mild after 2 sessions of DEX infusion. In contrast, at least 6 sessions of ECT treatment were needed to achieve a same level. Finally, the rates of therapeutic response and remission were comparable between the two groups. No serious adverse events were observed. CONCLUSIONS: Based on current published evidence, we conclude that DEX exhibits rapid and durable antidepressant properties similar to ECT but with fewer side effects.

Advance of tolerance engineering on microbes for industrial production.

Industrial microbes have become the core of biological manufacturing, which utilized as the cell factory for production of plenty of chemicals, fuels and medicine. However, the challenge that the extreme stress conditions exist in production is unavoidable for cell factory. Consequently, to enhance robustness of the chassis cell lays the foundation for development of bio-manufacturing. Currently, the researches on cell tolerance covered various aspects, involving reshaping regulatory network, cell membrane modification and other stress response. In fact, the strategies employed to improve cell robustness could be summarized into two directions, irrational engineering and rational engineering. In this review, the metabolic engineering technologies on enhancement of microbe tolerance to industrial conditions are summarized. Meanwhile, the novel thoughts emerged with the development of biological instruments and synthetic biology are discussed.

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.

Test-Retest Reliability and Random Measurement Error of the Multifactorial Memory Questionnaire in Older Adults With Subjective Memory Complaints.

To examine the psychometric properties of the Multifactorial Memory Questionnaire (MMQ) in older adults with subjective memory complaints. The three MMQ subscale (Satisfaction, Ability, and Strategy) was administered twice, with a 3-month interval. The test-retest reliability was examined using intraclass correlation coefficients (ICCs). The random measurement error was examined by calculating the standard error of measurement (SEM) and minimal detectable change (MDC95). The test-retest reliabilities of the three MMQ subscales were generally acceptable. The SEM of the three MMQ subscales was higher than the acceptable criterion of 10%. Despite the influence of random measurement error, the change scores of the three MMQ subscales may represent true changes if they are larger than the MDC95 of 13.2 (Satisfaction), 18.4 (Ability), and 16.9 (Strategy). The MMQ appears to be a reliable measure for use in research settings, but may not yet be suitable for clinical use.

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.

The Underling Mechanisms Exploration of Rubia cordifolia L. Extract Against Rheumatoid Arthritis by Integrating Network Pharmacology and Metabolomics.

Purpose: Rubia cordifolia L. (RC) is a classic herbal medicine for the treatment of rheumatoid arthritis (RA) and has been used since ancient times. The ethanol extract of Rubia cordifolia L. (RCE) showed obvious anti-RA effects in our previous study. However, further potential mechanisms require more exploration. We aimed to investigate the mechanism of RCE for the treatment of RA by integrating metabolomics and network pharmacology in this study. Methods: An adjuvant-induced arthritis (AIA) rat model was established, and we evaluated the therapeutic effects of RCE. Metabolomics of serum and urine was used to identify the differential metabolites. Network pharmacology was applied to determine the key metabolites and potential targets. Finally, the potential targets and compounds of RCE were verified by molecular docking. Results: The results indicated that RCE suppressed foot swelling and alleviated joint damage and also had anti-inflammatory properties by inhibiting the expressions of tumor necrosis factor (TNF)-α, Interleukin (IL)-1ß, prostaglandin E2 (PGE2), and P65. Ten and seven differential metabolites were found in the serum and urine, respectively, of rats. Six key targets, ie, phospholipase A2 group IIA (PLA2G2A), phospholipase A2 group X (PLA2G10), cytidine deaminase (CDA), uridine-cytidine kinase 2 (UCK2), charcot-leyden crystal galectin (CLC), and 5',3'-nucleotidase, mitochondrial (NT5M), were discovered by network pharmacology and metabolite analysis and were found to be related to glycerophospholipid metabolism and pyrimidine metabolism. Molecular docking confirmed that the favorable compounds showed affinities with the key targets, including alizarin, 6-hydroxyrubiadin, ruberythric acid, and munjistin. Conclusion: This study revealed the underlying mechanisms of RCE and provided evidence that will allow researchers to further investigate the functions and components of RCE against RA.