Analysis of the trajectory and influencing factors of kinesiophobia in elderly patients during the rehabilitation phase of limb fractures.

OBJECTIVES: To explore the trajectory and influencing factors of kinetophobia in elderly patients with limb fracture during the rehabilitation period. METHODS: In this retrospective study, we retrieved the follow-up records of 150 elderly patients with limb fractures from our hospital's electronic medical record system. We collected the demographic data and Tampa Scale for Kinesiophobia (TSK) scores of patients at postoperative day 1 (T0), 1 week (T1), 3 weeks (T2), 6 weeks (T3), and 12 weeks (T4) to track changes in kinesiophobia over time. We used Mplus 8.3 software to fit the development trajectory types of kinesiophobia based on TSK scores at time points T0 to T4 using a Latent Class Growth Model (LCGM). After selecting the best fitting model, logistic regression analysis was performed to identify the risk factors for kinesiophobia in different types. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare the predictive value of relevant influencing factors for kinetophobia in elderly patients recovering from limb fracture. RESULTS: The TSK scores decreased steadily from T0 to T4 [(46.03±7.88) at T0, (41.14±8.89) at T1, (34.61±5.64) at T2, (29.95±6.79) at T3, and (26.71±5.03) at T4], [F (4, 745) = 193.1, P < 0.001]. We identified the trajectory of changes in kinesiophobia symptoms through LCGM, gradually establishing models with 1 to 5 categories. By integrating the results of relevant fit indices, we ultimately selected the best fitting model with 2 categories. Among them, 119 patients in Class 1 (79.3%) showed a slow and continuous decline in kinesiophobia symptoms from T0 to T4, while 31 patients in Class 2 (20.7%) exhibited rapid decline followed by rebound in kinesiophobia symptoms. Logistic regression showed that older the age (OR = 1.219), per capita monthly income < 3000 yuan (OR = 12.657), numeric rating scale (NRS), patients with higher NRS (OR = 2.401) and higher self-efficacy (OR = 1.212) were more likely to be in Class 1. The ROC curve results show that the combined above indicators have a higher predictive value for the changes in fear of movement in elderly patients with lower limb fractures during the rehabilitation period (AUC = 0.934), compared to age (AUC = 0.694), per capita monthly income (AUC = 0.654), NRS score (AUC = 0.812), and self-efficacy (AUC = 0.811) as individual indicators. CONCLUSION: As the recovery time progresses for elderly patients with limb fractures, the overall trend of kinesiophobia scores decreases. Kinesiophobia presents with two different trajectories, with age, average monthly income, NRS score, and self-efficacy being important factors influencing the trajectory categories of kinesiophobia changes.

Research Progress of Novel Inorganic Nanomaterials in the Diagnosis and Treatment of Alzheimer's Disease.

The global increase in the number of Alzheimer's disease (AD) patients has posed numerous treatment challenges. Six Food and Drug Administration-approved medications (e.g., donepezil and memantine) have demonstrated some efficacy but are primarily used to alleviate symptoms. The etiology of AD is unknown, and the blood-brain barrier restricts drug penetration, which severely restricts the use of various therapeutic agents. With their high targeting, long-lasting effect, and multifunctionality, inorganic nanomaterials provide a novel approach to the treatment of AD. A review of inorganic nanoparticles in the diagnosis and therapy of AD. This paper reviews the research literature on the use of inorganic nanomaterials in the treatment of AD. Gold nanoparticles, superparamagnetic iron oxide nanoparticles, magnetic nanoparticles, carbon nanotubes, and quantum dots are among the inorganic nanomaterials studied. As knowledge of the origins of AD remains limited, the majority of studies on inorganic nanomaterials have primarily focused on interventions on Aß proteins. Adjusting and enhancing the properties of these inorganic nanomaterials, such as core-shell structure design and surface modification, confer benefits for the treatment of AD. Inorganic nanoparticles have a wide spectrum of therapeutic potential for AD. Despite their potential benefits, however, the safety and translation of inorganic nanomaterials into clinical applications remain formidable obstacles.

Non-Specific Elevated Serum Free Fatty Acids in Lung Cancer Patients: Nutritional or Pathological?

IMPORTANCE: The reprogramming of lipid metabolism is a significant feature of tumors, yet the circulating levels of fatty acids in lung cancer patients remain to be explored. Moreover, the association between fatty acid levels and related factors, including nutritional intake, tumor metabolism, and tumor immunity, has been rarely discussed. OBJECTIVES: To explore the differences in serum free fatty acids between lung cancer patients and healthy controls, and investigate the factors associated with this phenomenon. DESIGN AND PARTICIPANTS: A case-control study enrolled 430 primary lung cancer patients and 430 healthy controls. The whole population had a medium [Q1, Q3] age of 48.0 [37.0, 58.9] years, with females comprising 56% of the participants. The absolute quantification of 27 serum free fatty acids (FFAs) was measured using a liquid chromatography-mass spectrometry (LC-MS/MS) detection. Data, including dietary intake, blood indicators, and gene expression of lung tissues, were obtained from questionnaires, blood tests, and RNA-sequencing. Statistical differences in FFA levels between lung cancer patients and healthy controls were investigated, and related contributing factors were explored. RESULTS: Levels of 22 FFAs were significantly higher in lung cancer patients compared to those in healthy controls, with fold changes ranging from 1.14 to 1.69. Lung cancer diagnosis models built with clinical and FFA features yielded an area under the receiver operating characteristic curve (AUROC) of 0.830 (0.780-0.880). Total fatty acids (TFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) showed no significant dietary-serum associations, indicating that the elevations might not be attributed to an excessive intake of relevant fatty acids from the diet. For RNA-sequencing of lung tissues, among the 68 lipid metabolism genes, 26 genes showed significant upregulation (FDR < 0.05), while 33 genes exhibited significant downregulation, indicating the involvement of the fatty acids in the tumor metabolism. Through joint analysis with immune cells and inflammatory factors in the blood, fatty acids might exert suppressing effects on tumor immunity. CONCLUSIONS: Lung cancer patients had elevated levels of serum free fatty acids compared to healthy individuals. The elevations might not be attributed to an excessive intake of relevant fatty acids from the diet but related to pathological factors of tumor metabolism and immunity. These findings will complement research on fatty acid metabolism of lung cancer and provide insights into potential intervention targets.

A study on the effect of clinical intervention of evidence-based nursing measures on complications in patients after breast-conserving surgery.

BACKGROUND: Breast-conserving surgery is an important treatment for breast cancer, which not only eradicates the disease, but also protects the integrity of the breast, however, postoperative nausea and vomiting often bother patients. OBJECTIVE: This study examines the effects of evidence-based nursing practices on nausea and vomiting in patients after breast-conserving surgery, with the aim of providing new perspectives for clinical nursing practice. METHODS: One hundred and sixty patients who underwent breast-conserving surgery from January 2023 to December 2023 in Fudan University Shanghai Cancer Center were enrolled. The patients were divided into an intervention group (evidence-based nursing group) and a control group (conventional nursing group) using the random number table method, both groups comprised 80 patients. The control group used conventional nursing methods, and the intervention group added evidence-based nursing intervention on this basis. Comparative analysis focused on the incidence of nausea and vomiting, quality of life metrics, and postoperative satisfaction. RESULTS: In the intervention group, notably lower incidence rates of postoperative nausea and vomiting were observed compared to the control group within both the 0-24 hour and 24-48-hour postoperative periods (P< 0.05). Furthermore, the intervention group exhibited significantly higher scores across all five dimensions as well as the overall score of the FACT-B scale in comparison to the control group (P< 0.05), accompanied by heightened satisfaction with the nursing staff. CONCLUSION: This study demonstrated the positive clinical intervention effects of evidence-based nursing measures and emphasized their importance in improving postoperative nausea and vomiting and quality of life. Future studies are expected to incorporate evidence-based nursing practices into nursing care to improve patient recovery and overall quality of care.

Chirality-driven strong thioredoxin reductase inhibition.

Overexpression of thioredoxin reductase (TXNRD) plays crucial role in tumorigenesis. Therefore, designing TXNRD inhibitors is a promising strategy for targeted anticancer drug development. However, poor selectivity has always been a challenge, resulting in unavoidable toxicity in clinic. Herein we demonstrate a strategy to develop highly selective chiral metal complexes-based TXNRD inhibitors. By manipulating the conformation of two distinct weakly interacting groups, we optimize the compatibility between the drug and the electrophilic group within the active site of TXNRD to enhance their non-covalent interaction, thus effectively avoids the poor selectivity deriving from covalent drug interaction, on the basis of ensuring the strong inhibition. Detailed experimental and computational results demonstrate that the chiral isomeric drugs bind to the active site of TXNRD, and the interaction strength is well modulated by chirality. Especially, the meso-configuration, in which the two large sterically hindered active groups are positioned on opposite sides of the drug, exhibits the highest number of non-covalent interactions and most effective inhibition on TXNRD. Taken together, this work not only provides a novel approach for developing highly selective proteinase inhibitors, but also sheds light on possible underlying mechanisms for future application.

Impact analysis of dust evolution pattern and determination of key ventilation parameters in highland highway construction tunnels.

In order to study the influence of ventilation parameters on the ventilation of plateau highway construction tunnels, a highway tunnel construction section in Yunnan is taken as the research background, and Fluent software is used for simulation. The results of the study show that: under the conditions of press-in ventilation, the wind speed in the center of the vortex area in the wind flow field is smaller than the wind speed in the surrounding area, and with the diffusion of the flow field, the average wind speed in the tunnel section gradually decreases, and ultimately stabilizes at the level of 0.5 m/s. After blasting, the dust mass concentration on the return side of the tunnel is higher than that on the duct side. Dust with a particle size of 30 µm or more settled rapidly within 100 m from the boring face, while dust with a particle size of 30 µm or less gradually diffused outward under the action of the wind flow. In the vicinity of the tunnel boring face, reducing the distance from the air outlet to the boring face and increasing the air velocity can improve the dust removal effect. This conclusion can provide theoretical basis and certain guidance for the evolution of dust and dust prevention in the tunnel construction process in plateau area.

Clinical Guidelines on Compression Therapy in Venous Diseases.

BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (grade I), moderate (grade IIa and IIb), and weak (grade III) recommendations based on high-quality (class A), moderate-quality (class B), and low-quality (class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on 7 fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome (PTS), chronic venous insufficiency (CVI), varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (grade I) and 17 were based on high-quality (class A) evidence, highlighting the need for further research of the use of compression therapy.

Doughnut-shaped bimetallic Cu-Zn-MOF with peroxidase-like activity for colorimetric detection of glucose and antibacterial applications.

Metal-organic frameworks (MOFs), especially bimetallic MOFs, have attracted widespread attention for simulating the structure and function of natural enzymes. In this study, different morphologies of bimetallic Cu-Zn-MOF with different peroxidase (POD)-like activities were prepared by simply controlling the molar ratio of Cu2+ and Zn2+. Among them, the doughnut-shaped Cu9-Zn1-MOF exhibited the largest POD-like activity. Cu9-Zn1-MOF was combined with glucose oxidase to construct a sensitive and selective glucose colorimetric biosensor with a linear detection range of 10-300 µM and a detection limit of 7.1 µm. Furthermore, Cu9-Zn1-MOF can efficiently convert hydrogen peroxide (H2O2) into hydroxyl radicals that effectively kill both gram-negative and gram-positive bacteria at low H2O2 level. The results of this study may promote the synthesis of bimetallic MOFs and broaden their applications in the biomedical field.

Taking the Express Lane: Student Attitudes Towards Tracking in Ob/Gyn Residency.

We sought to determine the subspecialty interests of fourth-year medical students (MS4s) matched to Ob/Gyn and evaluate their attitudes towards residency tracking. Matched MS4s completed a survey regarding subspecialization, confidence in that choice, and desire for tracking. A total of 922 MS4s completed the survey. Of these, 474 (51.4%) desired subspecialty training, but were less confident in their choice compared with those desiring generalist careers (60.0/100 vs. 64.9/100, P =0.003). Those seeking subspecialty training were more likely to desire tracking (15.2% vs. 39.5%, P <0.001). In conclusion, 51% of MS4s desired subspecialty training over generalist careers. Almost 40% of these students are interested in tracking.

Clinical outcomes and aortic remodeling after Castor single-branched stent-graft implantation for type B aortic dissections involving left subclavian artery.

Background: The left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic endovascular aortic repair (TEVAR). The Castor single-branched stent graft is designed to treat type B aortic dissection (TBAD) to retain the LSA during TEVAR. This study investigates clinical outcomes, aortic remodeling, and abdominal aortic perfusion patterns after TEVAR with the novel Castor device. Methods: From November 2020 to June 2023, 29 patients with TBAD involving the LSA were treated with the Castor single-branched stent graft. In-hospital clinical outcome and aortic computed tomography angiography (CTA) data were analyzed. CTA was performed preoperatively and at follow-up to observe stent morphology; branch patency; endoleak; change in true lumen (TL), false lumen (FL), and transaortic diameters; and abdominal aortic branch perfusion pattern. Results: The technical success rate was 96.6%. One failure was that the branch section did not completely enter the LSA and the main body migrated distally. No in-hospital mortality, paraplegia, or stroke occurred. During follow-up, one type Ib endoleak, four distal new entry tears, and one recurrent type A dissection arose from a new entry tear at the ascending aorta, no stent migration was observed, and the branch patency rate was 100%. At the thoracic aorta, TL diameters significantly increased, FL diameters markedly decreased, and FL was partially or completely thrombosed in most patients at follow-up. At the abdominal aorta, we observed 33.3% of TL growth and 66.7% of TL stabilization or shrinkage. The initial TL ratio at iliac bifurcation negatively predicted abdominal TL growth after TEVAR with a cutoff of 21.0%. Of the 102 abdominal aortic branches, 94.1% of the branches showed no change in perfusion pattern, 3.9% of the branches had an increased TL perfusion, and 2.0% of the branches had an increased FL contribution. Conclusion: The Castor unibody single-branched stent graft offers an efficient endovascular treatment for TBAD involving the LSA. TEVAR with the Castor device effectively induced thoracic FL thrombosis and thoracic TL enlargement and resulted in abdominal TL growth when the initial TL ratio at iliac bifurcation is less than 21.0%. Abdominal aortic branch perfusion patterns remain relatively stable after TEVAR with the Castor stent graft.

Icotinib in a lung adenocarcinoma patient with acquired EGFR 19del/C797S mutation-mediated resistance to osimertinib: a case report.

Based on the FLAURA and AURA III trials, compared to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), osimertinib provides a longer overall survival benefit for patients with untreated EGFR mutated non-small cell lung cancer. Similar to other EGFR-TKIs, drug resistance is, however, inevitable. The most common mechanism of acquired resistance to first-line osimertinib therapy is the C797S mutation, which accounts for 6% of cases. In view of the current challenges of the development of the next generation of EGFR inhibitors, the mechanism of third-generation targeted drug resistances and targeted strategies are key for further exploration. Our case report discusses a female patient with advanced lung adenocarcinoma carrying the EGFR exon19 E746_A750delinsIP mutation who received osimertinib as first-line therapy and acquired C797S resistance during treatment. The patient was then treated with icotinib for 8 months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.

CEACAM6 expression and function in tumor biology: a comprehensive review.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily protein primarily expressed on epithelial surfaces and myeloid cells. It plays a significant role in cancer progression by inhibiting apoptosis, promoting drug resistance, and facilitating cancer cell invasion and metastasis. Overexpression of CEACAM6 has been observed in various cancers, including lung, breast, colorectal, and hepatocellular cancers, and is associated with poorer overall survival and disease-free survival. Its differential expression on tumor cell surfaces makes it a promising cancer marker. This review aims to provide a comprehensive summary of CEACAM6's role in different cancer types, its involvement in signaling pathways, and recent advancements in CEACAM6-targeted treatments.

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway.

Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1ß, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.

A new species and a replacement name in Cynanchum (Apocynaceae, Asclepiadeae) from China.

Cynanchumpingtaoi S.Jin Zeng, G.D.Tang & Miao Liao, sp. nov. (Apocynaceae) from Yunnan Province, China, is described and illustrated based on morphological and molecular evidence. Its deeply cordate to reniform leaves and campanulate, large flowers show that it is a member of former Raphistemma Wall., which has been included in Cynanchum L.. It is different from all former Raphistemma species by the broadly ovate corolla lobes, purple-red corolla and connivent corona tip slightly exceeding the corolla throat. Meanwhile, Cynanchumlonghushanense G.D.Tang & Miao Liao, nom. nov. is proposed as replacement name for Raphistemmabrevipedunculatum Y.Wan, which was considered a synonym of Cynanchumhooperianum (Blume) Liede & Khanum but is here reinstated as a distinct species because of significant morphological differences.

Disulfide-constrained peptide scaffolds enable a robust peptide-therapeutic discovery platform.

Peptides present an alternative modality to immunoglobulin domains or small molecules for developing therapeutics to either agonize or antagonize cellular pathways associated with diseases. However, peptides often suffer from poor chemical and physical stability, limiting their therapeutic potential. Disulfide-constrained peptides (DCP) are naturally occurring and possess numerous desirable properties, such as high stability, that qualify them as drug-like scaffolds for peptide therapeutics. DCPs contain loop regions protruding from the core of the molecule that are amenable to peptide engineering via direct evolution by use of phage display technology. In this study, we have established a robust platform for the discovery of peptide therapeutics using various DCPs as scaffolds. We created diverse libraries comprising seven different DCP scaffolds, resulting in an overall diversity of 2 x 1011. The effectiveness of this platform for functional hit discovery has been extensively evaluated, demonstrating a hit rate comparable to that of synthetic antibody libraries. By utilizing chemically synthesized and in vitro folded peptides derived from selections of phage displayed DCP libraries, we have successfully generated functional inhibitors targeting the HtrA1 protease. Through affinity maturation strategies, we have transformed initially weak binders against Notch2 with micromolar Kd values to high-affinity ligands in the nanomolar range. This process highlights a viable hit-to-lead progression. Overall, our platform holds significant potential to greatly enhance the discovery of peptide therapeutics.

Extensive Stage Small-Cell Lung Cancer with Cystic Brain Metastases: A Report of Two Cases.

Objective: Cystic brain metastases (BMs) are rare in small cell lung cancer (SCLC), and there are limited data on the treatment and prognosis of cystic BMs. Whole brain radiotherapy has been the mainstay for BMs since several years. Immune checkpoint inhibitors in extensive stage small cell lung cancer (ES-SCLC) have been shown to be suitable for patients who experienced better overall survival and progress-free survival and have been approved as the first-line treatment for ES-SCLC. In this report, we described two ES-SCLC patients developed cystic BMs after immunotherapy, after which the patients continued to treat the primary lesion with immune checkpoint inhibitors and the cystic BMs with radiotherapy. Case Description: Two male patients were diagnosed with ES-SCLC at the first admission and were subsequently treated with immunotherapy plus platinum therapy, during which cystic BMs developed. One patient received whole brain radiotherapy and the other received whole brain radiotherapy and Gamma knife radiosurgery (GKRS). Immunotherapy was continued after the brain lesions were controlled. It has been 33 months since the first patient was diagnosed and is now in stable condition. The other patient achieved an overall survival of 30 months. Conclusion: This report describes two patients with cystic brain metastases in ES-SCLC. Whole brain radiotherapy has a good effect on local control of cystic brain metastases in small cell lung cancer and can significantly improve the symptoms of patients. At the same time, we treat immunotherapy as the first-line treatment, and then perform cross-immunotherapy after disease progression, combined with anti-vascular targeting drugs. The patient did not develop severe iRAEs.

Comparison of metabolic rates of ropivacaine in cerebrospinal fluid as inferred from plasma concentrations between elderly patients and young patients.

BACKGROUND: With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. METHODS: Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18-30 years old and 75-90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aß protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. RESULTS: The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aß protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. CONCLUSIONS: This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people.

Role of MARK2 in the nervous system and cancer.

Microtubule-Affinity Regulating Kinase 2 (MARK2), a member of the serine/threonine protein kinase family, phosphorylates microtubule-associated proteins, playing a crucial role in cancer and neurodegenerative diseases. This kinase regulates multiple signaling pathways, including the WNT, PI3K/AKT/mTOR (PAM), and NF-κB pathways, potentially linking it to cancer and the nervous system. As a crucial regulator of the PI3K/AKT/mTOR pathway, the loss of MARK2 inhibits the growth and metastasis of cancer cells. MARK2 is involved in the excessive phosphorylation of tau, thus influencing neurodegeneration. Therefore, MARK2 emerges as a promising drug target for the treatment of cancer and neurodegenerative diseases. Despite its significance, the development of inhibitors for MARK2 remains limited. In this review, we aim to present detailed information on the structural features of MARK2 and its role in various signaling pathways associated with cancer and neurodegenerative diseases. Additionally, we further characterize the therapeutic potential of MARK2 in neurodegenerative diseases and cancer, and hope to facilitate basic research on MARK2 and the development of inhibitors targeting MARK2.

Mining significant local spatial association rules for multi-category point data.

Spatial association rule mining can reveal the inherent laws of spatial object interdependence and is an important part of spatial data mining. Most of the existing algorithms for mining local spatial association rules are oriented towards the spatial association between two categories of points and cannot fully reflect the spatial heterogeneity of complex spatial relations among multiple categories of points. In addition, the interactions between points in different categories are often asymmetrical. However, the existing algorithms ignore this asymmetry. To address the above problems, an algorithm for mining local spatial association rules for point data of multiple categories based on position quotients is proposed. First, the proximity relationship between points is determined by an adaptive filter, and the spatial weight value is given according to Gaussian kernel function. Then, the multivariate local colocation quotient of each point is calculated to measure the strength of the local regional spatial association rule. Finally, the Monte Carlo simulation function is used to generate a random sample distribution to test the significance of the results. The algorithm is verified on artificial simulation data and real Point of Interest (POI) data. The experimental results show that the algorithm can identify significant association regions of different spatial association rules for point sets.

Network pharmacology to unveil the mechanism of suanzaoren decoction in the treatment of alzheimer's with diabetes.

BACKGROUND: Suanzaoren Decoction (SZRD), a well-known formula from traditional Chinese medicine, has been shown to have reasonable cognitive effects while relaxing and alleviating insomnia. Several studies have demonstrated significant therapeutic effects of SZRD on diabetes and Alzheimer's disease (AD). However, the active ingredients and probable processes of SZRD in treating Alzheimer's with diabetes are unknown. This study aims to preliminarily elucidate the potential mechanisms and potential active ingredients of SZRD in the treatment of Alzheimer's with diabetes. METHODS: The main components and corresponding protein targets of SZRD were searched on the TCMSP database. Differential gene expression analysis for diabetes and Alzheimer's disease was conducted using the Gene Expression Omnibus database, with supplementation from OMIM and genecards databases for differentially expressed genes. The drug-compound-target-disease network was constructed using Cytoscape 3.8.0. Disease and SZRD targets were imported into the STRING database to construct a protein-protein interaction network. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the intersection of genes. Molecular docking and molecular dynamics simulations were conducted on the Hub gene and active compounds. Gene Set Enrichment Analysis was performed to further analyze key genes. RESULTS: Through the Gene Expression Omnibus database, we obtained 1977 diabetes related genes and 622 AD related genes. Among drugs, diabetes and AD, 97 genes were identified. The drug-compound-target-disease network revealed that quercetin, kaempferol, licochalcone a, isorhamnetin, formononetin, and naringenin may be the core components exerting effects. PPI network analysis identified hub genes such as IL6, TNF, IL1B, CXCL8, IL10, CCL2, ICAM1, STAT3, and IL4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that SZRD in the treatment of Alzheimer's with diabetes is mainly involved in biological processes such as response to drug, aging, response to xenobiotic, and enzyme binding; as well as signaling pathways such as Pathways in cancer, Chemical carcinogenesis - receptor activation, and Fluid shear stress and atherosclerosis. Molecular docking results showed that licochalcone a, isorhamnetin, kaempferol, quercetin, and formononetin have high affinity with CXCL8, IL1B, and CCL2. Molecular dynamics simulations also confirmed a strong interaction between CXCL8 and licochalcone a, isorhamnetin, and kaempferol. Gene Set Enrichment Analysis revealed that CXCL8, IL1B, and CCL2 have significant potential in diabetes. CONCLUSION: This study provides, for the first time, insights into the active ingredients and potential molecular mechanisms of SZRD in the treatment of Alzheimer's with diabetes, laying a theoretical foundation for future basic research.