Apoptotic metabolites ameliorate bone aging phenotypes via TCOF1/FLVCR1-mediated mitochondrial homeostasis.

Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.

CpG Methylation of Receptor Activator NF-κB (RANK) Gene Promoter Region Delineates Senescence-Related Decrease of RANK Gene Expression.

While the rapid decrease in estrogen is well known as the main cause of postmenopausal osteoporosis in women, the precise pathogenesis of senile osteoporosis in the elderly regardless of gender is largely unknown. The age-related epigenetic regulation of receptor activator NF-κB (RANK) gene expression was investigated with the use of a high-passaged mouse osteoclast progenitor cell line, RAW264.7, as an in vitro model of aging. In the RAW264.7 cells after repeated passages, receptor RANK expression was downregulated, resulting in decreased soluble RANK ligand (sRANKL)-induced osteoclastogenesis, expression of tartrate-resistant acid phosphatase-5b (TRAcP) and cathepsin K (CTSK). Methylation-specific PCR and bisulfite mapping revealed hypermethylation of CpG-loci located in the RANK gene promoter in multiple-passaged cells. ICON probe-mediated in situ assessment of methylated-cytosine at the CpG loci revealed an increase in the percentage of methylated RAW264.7 cells in the RANK gene in a passage-dependent manner. Conversely, upon treatment with demethylating agent 5-aza-2-deoxycytidine (5-aza-dC), high-passaged RAW264.7 cells displayed restored expression of the RANK gene, osteoclastogenesis, TRAcP and CTSK. Ex vivo cultures of splenic macrophages from young (10.5 W) and aged (12 M) mice also showed that CpG methylation was predominant in the aged animals, resulting in reduced RANK expression and osteoclastogenesis. Reduced RANK expression by age-related accumulation of DNA methylation, albeit in a limited population of osteoclast precursor cells, might be, at least in part, indicative of low-turnover bone characteristic of senile osteoporosis.

Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.

With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs. However, Prx1-driven Bmi-1 overexpression showed a contrasting phenotype to Prx1-driven Bmi-1 knockout in BMSCs. Regarding mechanism, Bmi-1-RING1B bound to DNMT3A and promoted its ubiquitination and inhibited DNA methylation of Runx2 at the region from 45047012 to 45047313 bp, thus promoting the osteogenic differentiation of BMSCs. Moreover, Bmi-1-EZH2 repressed the transcription of Cebpa by promoting H3K27 trimethylation at the promoter region -1605 to -1596 bp, thus inhibiting the adipogenic differentiation of BMSCs. It is also found that Prx1-driven Bmi-1 overexpression rescued the SOP induced by Prx1-driven Bmi-1 knockout in BMSCs. Thus, Bmi-1 functioned as a hub protein in the epigenetic regulation of BMSCs differentiation to delay bone aging. The Prx1-driven Bmi-1 overexpression in BMSCs can be used as an approach for the translational therapy of SOP.

Effectiveness of bone-filled mesh bag technology and angle vertebroplasty in the treatment of osteoporotic thoracic vertebral compression fractures in the elderly.

OBJECTIVE: To evaluate the effectiveness, pain level, and lung function in elderly patients with osteoporotic thoracic vertebral compression fractures using bone filling mesh bag technology compared to curved vertebroplasty. METHODS: This retrospective analysis reviewed 72 elderly patients with osteoporotic thoracic vertebral compression fractures treated at Xindu District People's Hospital of Chengdu between February 2021 and January 2022. The patients were separated into two groups according to surgery approach: an observation group using bone filling mesh bag technology and a control group using curved vertebroplasty. The overall response rate, pain degree, pulmonary function, life quality grades, surgical indicators, and bone cement leakage rates of the two groups were evaluated. RESULTS: The variation in overall response rate (P=0.420), pain degree (P=0.270), pulmonary function (peak expiratory flow: P=0.660, forced expiratory volume in the first second: P=0.775, forced vital capacity: 0.062), and life quality grades (physical health: P=0.949, social function: P=0.935, physiological function: P=0.970, vitality: P=0.778) between the observation group and the control group after treatment was not statistically meaningful. The Cobb angle (P<0.001) and vertebral height (P<0.001) of patients in the observation group were significantly higher than those in the control group after therapy. The leakage rates of bone cement (intervertebral disc leakage, paravertebral vein leakage, paravertebral soft tissue leakage) of patients in the observation group were notably lower than those in the control group after therapy (P=0.029). CONCLUSION: Bone filling mesh bag technology offers significant improvements in Cobb angle and vertebral height for treating elderly patients with osteoporotic thoracic vertebral compression fractures, and reduced the leakage rate of bone cement. This technique achieves comparable therapeutic outcomes to curved vertebroplasty.

Acupuncture for senile insomnia: A systematic review of acupuncture point.

OBJECTIVE: Insomnia is one of the most common diseases among the elderly. The elderly with long-term insomnia are more likely to have symptoms such as vertigo, fatigue, and immunity decline. Acupuncture is increasingly being used to treat insomnia. The purpose of this review is to summarize the critical acupoints in the treatment of senile insomnia and evaluate the effectiveness of the treatment. To provide a research basis for acupuncture treatment of senile insomnia in the future. METHODS: We will search the clinical studies on acupuncture in the treatment of senile insomnia published by CNKI (China National Knowledge Infrastructure), Wanfang (Wan Fang Data Knowledge Service Platform), CSTJ (China Science and Technology Journal Database), Pubmed, and ScienceDirect before December 31, 2023. Acupoint will be analyzed using TCMISS (TCM Inheritance Assistance Platform). RESULTS: 265 literatures were retrieved, and 94 were selected as the criteria. The results showed that there were 90 acupoints related to treatment. The acupoints with the highest frequency were shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), neiguan (PC6), xinshu (BL15), taixi (KI3), and sishencong (EX-HN1) anmian (JLSXX-QX), shenshu (BL23). The most frequently used meridians were bladder meridian (BL), governor vessel (GV), and stomach meridian (ST). They were mainly distributed in the lower limbs and head. The most frequent specific points are the five transport points and source points. The most frequently used combinations are "shenmen (HT7) - sanyinjiao (SP6)", "shenmen (HT7) - baihui (GV20)", and "shenmen (HT7) - neiguan (PC6)". Association rule analysis showed that the acupoints with the highest confidence were shenmen (HT7), neiguan (PC6), and sanyinjiao (SP6). Network topology analysis showed that sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) were the core acupuncture points for the treatment of senile insomnia. CONCLUSION: The primary Acupuncture acupoints for senile insomnia are shenmen (HT7), sanyinjiao (SP6), baihui (GV20), zusanli (ST36), and neiguan (PC6), indicating that these acupoints have a strong correlation with senile insomnia. Sanyinjiao (SP6), zusanli (ST36), and shenmen (HT7) may be the core acupuncture acupoints for the treatment of senile insomnia.

Effect of Comprehensive Rehabilitation Training Based on Balance Function on Postoperative Recovery and Function of Hip Fracture in the Elderly: A Systematic Review and Meta-Analysis.

Introduction: In China, the proportion of the elderly population is gradually increasing, followed by the increasing medical demands of elderly patients. Hip fracture is a common fracture in the elderly. The elderly are prone to serious postoperative complications, resulting in failure to restore normal hip function, which seriously affects patients' quality of life and further increases their mortality rate. Thus, hip fracture represents a remarkable public health issue within the realm of geriatric medical care. Significance: This study systematically evaluated the impact of comprehensive rehabilitation training, with a focus on balance function, on elderly individuals with hip fractures' postoperative recovery and functional outcomes. Result: Results showed a significant difference in BBS scores favoring comprehensive rehabilitation training based on balance function over conventional intervention. Similarly, AM-PAC scores favored the balance-focused training. TUTG meta-analysis indicated its adoption in comprehensive rehabilitation training. FIM scores showed improvement with balance-focused training. Harris score meta-analysis also favored this approach. A funnel plot analysis revealed potential publication bias, likely due to study heterogeneity and limited publications. Conclusions: In conclusion, comprehensive rehabilitation training centered around balance function displayed clinical efficacy in enhancing postoperative hip joint function in elderly hip fracture patients. This approach improved balance, coordination, and posture control, facilitating lower limb function recovery and overall prognosis. It holds promise as a valuable treatment approach.

Network analysis combined with experimental assessment to explore the therapeutic mechanisms of New Shenqi Pills formula targeting mitochondria on senile diabetes mellitus.

Background: The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM's renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics. Aims: The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment. Methods: Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet ß cells. Results: In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, ß-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3ß protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet ß cells. Conclusion: Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3ß pathway plays an important regulatory role in this process.

Effects of comprehensive exercise training on frailty, negative emotions and physical functions of elderly patients with diabetes.

Objective: To evaluate the effects of comprehensive exercise training on frailty, negative emotions and physical functions of elderly patients with diabetes. Methods: This is a retrospective study. A total of 140 elderly patients with T2DM in The No.2 Hospital of Baoding were selected from December, 2021 to June, 2023 and randomly divided into two groups, with 70 patients in each group. The control group was given routine nursing and routine exercise education, and the study group was additionally given comprehensive exercise training. Tilburg frailty indicator (TFI), emotional status, physical functions, grip strength, fasting blood glucose and patient satisfaction were compared and analyzed between the two groups. Results: Before the intervention, TFI showed no significant differences between the two groups (p>0.05). After the intervention, physical, psychological and social frailty in the study group were significantly lower than those in the control group, with statistically significant differences (p= 0.00). SAS and SDS scores reduced significantly in the study group compared with those in the control group after the intervention, with statistically significant differences (p=0.00). After the intervention, the grip strength was significantly larger while the fasting blood glucose was significantly lower in the study group compared with those in the control group, with statistically significant differences (p=0.00). Patient satisfaction in the study group was higher than in the control group, with a statistically significant difference(p=0.03). Conclusion: Comprehensive exercise training for elderly patients with diabetes is beneficial to improving their frail state, negative emotions, blood glucose levels and physical functions. It has significant clinical application value.

Assessing the current situation and the influencing factors affecting perceived stigma among older patients after leukemia diagnosis.

BACKGROUND: Psychological problems are becoming increasingly prominent among older patients with leukemia, with patients potentially facing stigmatization after diagnosis. However, there is limited research on the stigma experienced by these patients and the factors that may contribute to it. AIM: To investigate the stigma faced by older patients after being diagnosed with leukemia and to analyze the potential influencing factors. METHODS: A retrospective analysis was conducted using clinical data obtained from questionnaire surveys, interviews, and the medical records of older patients with leukemia admitted to the Hengyang Medical School from June 2020 to June 2023. The data obtained included participants' basic demographic information, medical history, leukemia type, family history of leukemia, average monthly family income, pension, and tendency to conceal illness. The Chinese versions of the Social Impact Scale (SIS), Perceived Social Support Scale (PSSS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were used to assess indicators related to stigma, social support, and mental health status. We used Pearson's correlation coefficient to analyze the strength and direction of the relationship between the scores of each scale, and regression analysis to explore the factors related to the stigma of older patients with leukemia after diagnosis. RESULTS: Data from 120 patients with leukemia aged 65-80 years were analyzed. The total score on the SIS and PSSS was 43.60 ± 4.07 and 37.06 ± 2.87, respectively. The SAS score was 58.35 ± 8.32 and the SDS score was 60.58 ± 5.97. The stigma experienced by older leukemia patients was negatively correlated with social support (r = -0.691, P < 0.05) and positively correlated with anxiety and depression (r = 0.506, 0.382, P < 0.05). Age, education level, smoking status, average monthly family income, pension, and tendency to conceal illness were significantly associated with the participants' level of stigma (P < 0.05). Age, smoking status, social support, anxiety, and depression were predictive factors of stigmatization among older leukemia patients after diagnosis (all P < 0.05), with a coefficient of determination (R2) of 0.644 and an adjusted R2 of 0.607. CONCLUSION: Older patients commonly experience stigmatization after being diagnosed with leukemia. Factors such as age, smoking status, social support, and psychological well-being may influence older patients' reported experience of stigma.

Systemic Vascular Parameters in Ocular Pseudoexfoliation.

Background Pseudoexfoliation syndrome (PEX) is characterized by a dandruff-like substance in the anterior chamber, composed of various glycoproteins that have an unclear origin. Its deposition is observed on the pupillary margin, lens zonules, and trabecular meshwork. Proteomic studies have identified numerous proteins in the affected individuals, suggesting associations with systemic conditions like heart disease, stroke, and Alzheimer's disease. However, the systemic associations of PEX remain inconclusive, particularly in regions like southern India. Materials and methods A cross-sectional study was conducted on 114 participants. Pseudoexfoliation was graded as mild, moderate, and severe as per standard photographic grading. Systemic examinations included blood pressure measurements, electrocardiography (ECG), and blood investigations for serum lipid profile, fasting and postprandial blood sugar levels, and serum C-reactive protein levels. Small incision cataract surgery was performed for all the patients. Intraoperative complications and postoperative status were recorded. Results Thirty-eight patients (33.3%) had mild PEX, 44 (38.6%) had moderate PEX, and 32 (28.1%) had severe PEX. Hypertension was present in 54 participants (47.4%), diabetes in 21 (18.4%), coronary artery disease in nine (7.9%), and cerebrovascular accidents in three (2.6%). The mean systolic blood pressure was 140.39 mmHg and the mean diastolic blood pressure was 90.37 mmHg. Systolic blood pressure exceeded 140 mmHg in 29 participants (90.6%) with severe PEX, while diastolic blood pressure surpassed 90 mmHg in 26 participants with severe PEX, both with a p-value of 0.001. Mean fasting and postprandial blood sugar levels were 103.80 ± 31.81 mg/dl and 131.72 ± 48.24 mg/dl, respectively. Serum lipid profiles showed mean low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), cholesterol, and triglyceride levels of 103.00 ± 34.49 mg/dl, 29.04 ± 15.51 mg/dl, 172.73 ± 43.34 mg/dl, and 129.33 ± 64.65 mg/dl respectively. Electrocardiographic results indicated that 54 participants (47.37%) had abnormal ECG including rate abnormality in 13.2%, conduction defects in 12.3%, ischemic changes in 10.5%, and structural defects in 11.4%. Eighty-seven percent of patients had non-dilating pupils and iris atrophy, 13.2% had zonular dialysis and intraoperatively, 78% had capsulorhexis extension, 49.12% had difficult nucleus prolapse, and 28.95% had posterior capsular rent. Conclusion This study highlights the significantly elevated parameters of systemic vascular diseases in PEX patients, like elevated blood pressure and more frequent cardiac anomalies, emphasizing the need for comprehensive systemic evaluation and careful preoperative assessment for ocular comorbidities.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

[Impaired hemostasis in elderly and senile patients with mesenteric thrombosis in COVID-19.]

In the treatment of coronavirus infections, it is important not only to understand the course of the disease, but also to understand what is happening in the human body, especially in the circulatory system, that is, which disorders lead to deterioration and further complications. Hemostasis disorder in COVID-19 plays an important role in the etiology and clinical manifestations of the disease. The ability to identify factors and risk groups for the development of thrombotic complications, the ability to dynamically interpret peripheral blood parameters and coagulograms, knowledge of diagnostic criteria for possible hemostasis disorders (for example, DIC syndrome, sepsis-associated coagulopathy, antiphospholipids, hemophagocytosis and hypercoagulation syndrome) are necessary to determine the indications for the test. Differentiated prescribing of clinically justified therapy (including anticoagulants and blood components) is important, which determines the complexity of treatment and prognosis for patients with COVID-19. This article is a review of the literature on the topic of hemostasis disorders in elderly and senile patients with mesenteric thrombosis in COVID 19 over the past few years.

Prescription glucocorticoid medication and iridocyclitis are associated with an increased risk of senile cataract occurrence: a Mendelian randomization study.

Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.

Distinct patterns of plaque and microglia glycosylation in Alzheimer's disease.

Glycosylation is the most common form of post-translational modification in the brain. Aberrant glycosylation has been observed in cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) cases, including dysregulation of terminal sialic acid (SA) modifications. While alterations in sialylation have been identified in AD, the localization of SA modifications on cellular or aggregate-associated glycans is largely unknown because of limited spatial resolution of commonly utilized methods. The present study aims to overcome these limitations with novel combinations of histologic techniques to characterize the sialylation landscape of O- and N-linked glycans in autopsy-confirmed AD post-mortem brain tissue. Sialylated glycans facilitate important cellular functions including cell-to-cell interaction, cell migration, cell adhesion, immune regulation, and membrane excitability. Previous studies have not investigated both N- and O-linked sialylated glycans in neurodegeneration. In this study, the location and distribution of sialylated glycans were evaluated in three brain regions (frontal cortex, hippocampus, and cerebellum) from 10 AD cases using quantitative digital pathology techniques. Notably, we found significantly greater N-sialylation of the Aß plaque microenvironment compared with O-sialylation. Plaque-associated microglia displayed the most intense N-sialylation proximal to plaque pathology. Further analyses revealed distinct differences in the levels of N- and O-sialylation between cored and diffuse Aß plaque morphologies. Interestingly, phosphorylated tau pathology led to a slight increase in N-sialylation and no influence of O-sialylation in these AD brains. Confirming our previous observations in mice with novel histologic approach, these findings support microglia sialylation appears to have a relationship with AD protein aggregates while providing potential targets for therapeutic strategies.

Zhuang-Gu-Fang promotes osteoblast differentiation via myoblasts and myoblast-derived exosomal miRNAs:miR-5100, miR-126a-3p, miR-450b-5p, and miR-669a-5p.

BACKGROUND: Senile osteoporosis (SOP) is an age-related systemic metabolic bone disorder. Previous studies have proved that Zhuang-Gu-Fang (ZGF) modulates myokines, stimulates osteogenic differentiation, and mitigates osteoporosis. OBJECTIVE: To elucidate the mechanism by which ZGF promotes osteogenic differentiation via myoblast and myoblast exosomal microRNAs (miRNAs) and investigate its potential implications in senile osteoporosis. METHODS: Characterization of ZGF and ZGF serum using UHPLC-MS/MS. An alkaline phosphatase (ALP) activity assay and staining techniques were employed to corroborate the impacts of ZGF on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via myoblasts. Subsequently, exosomes derived from myoblasts were isolated through ultracentrifugation. The effects of ZGF on the BMSCs' osteogenic differentiation were substantiated through ALP activity, alizarin red staining, and a quantitative real-time polymerase reaction system (qRT-PCR). Selected miRNAs were identified via high-throughput sequencing and subjected to differential expression analysis, and subsequently validated through qRT-PCR. The senescence-accelerated (SAMP6) mice were selected as the SOP models. qRT-PCR analyses were further conducted to confirm the expression levels of these selected miRNAs in the muscle and bone tissues of the SAMP6 mice, and the protein expression of osteogenesis-related transcription factors OCN and Osterix in its bone tissue was evaluated by immunofluorescence staining analysis (IF). RESULTS: ZGF may enhance the osteogenic differentiation of BMSCs through myoblasts and myoblast-derived exosomes. High-throughput sequencing, differential expression analysis, and subsequent qRT-PCR validation identified four miRNAs that stood out due to their significant differential expression: miR-5100, miR-142a-3p, miR-126a-3p, miR-450b-5p and miR-669a-5p. Moreover, the mice experiment corroborated these findings, which revealed that ZGF not only up-regulated the expression of miR-5100, miR-450b-5p and miR-126a-3p in muscle and bone tissues but also concurrently down-regulated the expression of miR-669a-5p in these tissues. IF staining analysis indicated that ZGF can significantly increase the protein expression of the osteogenic transcription factors OCN and Osterix in the bone tissue of mice with SOP. CONCLUSIONS: ZGF can promote osteogenic differentiation of osteoblasts, regulate bone metabolism, and thereby delay the process of SOP. Perhaps, its mechanism is to upregulate myoblast-derived exosomes miR-5100, miR-126a-3p, and miR-450b-5p or downregulate miR-669a-5p. This study reports for the first time that myoblast exosomes miR-669a-5p and miR-450b-5p are novel targets for the regulation of osteoblastic differentiation and the treatment of SOP.

Based on the relationship between anxiety of existential meaninglessness, hope level, and fear of progression, explored the effect of preoperative nursing with Orem theory in the senile cataract population.

Background: Cataracts, characterized by a decrease in vision due to the clouding of the lens, can progress to blindness in advanced stages. The rising incidence of cataract cases has led to a significant number of patients experiencing negative emotions associated with vision loss, thereby diminishing their quality of life. In clinical practice, it is imperative for healthcare professionals to consider the psychological well-being of cataract patients. Currently, there is a scarcity of research focusing on psychological evaluations, such as assessing feelings of meaninglessness among individuals with cataracts. Objective: This study aims to investigate the factors influencing the anxiety of existential meaninglessness and to explore the relationships among existential anxiety, Herth hope index levels and fear of progression in the elderly cataract-affected population. Additionally, it evaluates the effectiveness of Orem's nursing care strategies. Methods: Utilizing a sociodemographic questionnaire, the Existential Meaninglessness Anxiety Scale (EM-A), Herth Hope Index Level Scale, and the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), this research employed convenience sampling for a cross-sectional and intervention study. The retrospective study sample comprised 1,029 individuals, while the intervention study included 317. The intervention design assessed psychological changes in existential meaninglessness following Orem's preoperative nursing interventions. Multiple linear regression analysis was employed to ascertain the determinants of EM-A within the population of elderly patients with senile cataracts. Pearson correlation analysis elucidated the relationship between EM-A, levels of hope, and the FoP-Q-SF among this demographic. Subsequent investigations, utilizing a t-test, evaluated the effects by comparing the data before and after the implementation of the interventions. Results: The correlation between EM-A, hope levels, and FoP-Q-SF was statistically significant (p < 0.05). Factors such as age, education level, alcohol consumption habits, hope levels, and FoP-Q-SF scores significantly affected EM-A scores (p < 0.05). Orem's nursing framework significantly reduced existential anxiety (p < 0.05). Conclusion: Among elderly patients with cataracts, existential anxiety was generally moderate. Hope levels and fear of progression were closely associated with the EM-A. The novel Orem preoperative care model effectively addresses clinical issues. In clinical practice, it is crucial to address psychological problems and enhance patients' quality of life.

Clinical study on the influence of phacoemulsification on retinal structure of senile cataract based on data mining.

BACKGROUND: With the improvement of the level of science and technology, diagnosis and treatment technology of ophthalmology has continuously improved, especially with the rise of optical coherence tomography. Alternative methods have enabled clinicians to obtain more information and make greater breakthroughs in the occurrence and development of many ophthalmic diseases. OBJECTIVE: To investigate changes in retinal structure in the macular area of senile diabetic cataract patients undergoing cataract phacoemulsification. METHODS: This was a prospective cohort study. A total of 68 cataract patients (78 eyes) who voluntarily received phacoemulsification combined with intraocular lens implantation in the Department of Ophthalmology of our hospital from December 2018 to December 2021 were selected. They were divided into A (diabetic) and B (non-diabetic) according to whether they were complicated with diabetes. There were 24 cases (28 eyes) in A and 44 cases (50 eyes) in B. Cataract patients were collected before and after surgery. Day, 1 week, and 1 month, data on the average thickness of the fovea retina and thickness of the retinal nerve fiber layer around the optic disc (average thickness, nasal thickness, topic side thickness, upper thickness, and lower thickness) were statistically analyzed analyze. RESULTS: The average retinal thickness of the macular fovea in Group A was found to be greater than that of Group B, however, there was no statistically significant difference between the two groups. At week one and week thirty, Group A's layer of retinal nerve fibers surrounding the optic disc thickened; there was no discernible difference between the two groups. One week and one month following surgery, however, showed a one-week difference in upper thickness compared to preoperative days. There was no discernible change between the preoperative and 1-day times. CONCLUSION: Both diabetic cataract patients and simple age-related cataract patients will have different degrees of increased foveal retinal thickness after surgery. However, the foveal retinal thickness of patients with diabetes increases more.