Cancer cost-related subjective financial distress among breast cancer: a scoping review.

PURPOSE: This article provided a comprehensive scoping review, synthesizing existing literature on the financial distress faced by breast cancer patients. It examined the factors contributing to financial distress, the impact on patients, coping mechanisms employed, and potential alleviation methods. The goal was to organize existing evidence and highlight possible directions for future research. METHODS: We followed the scoping review framework proposed by the Joanna Briggs Institute (JBI) to synthesize and report evidence. We searched electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, for relevant literature. We included English articles that met the following criteria: (a) the research topic was financial distress or financial toxicity, (b) the research subjects were adult breast cancer patients, and (c) the article type was quantitative, qualitative, or mixed-methods research. We then extracted and integrated relevant information for reporting. RESULTS: After removing duplicates, 5459 articles were retrieved, and 43 articles were included based on the inclusion and exclusion criteria. The articles addressed four main themes related to financial distress: factors associated with financial distress, impact on breast cancer patients, coping mechanisms, and potential methods for alleviation. The impact of financial distress on patients was observed in six dimensions: financial expenses, financial resources, social-psychological reactions, support seeking, coping care, and coping lifestyle. While some studies reported potential methods for alleviation, few discussed the feasibility of these solutions. CONCLUSIONS: Breast cancer patients experience significant financial distress with multidimensional impacts. Comprehensive consideration of possible confounding factors is essential when measuring financial distress. Future research should focus on exploring and validating methods to alleviate or resolve this issue.

A new classification for emergency critically ill patients and analysis of their adverse events during intrahospital transport: A cluster analysis.

BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.

Critical miRNAs in regulating pulmonary hypertension: A focus on Signaling pathways and therapeutic Targets.

Pulmonary hypertension (PH) is complex disease as a result of obstructive pulmonary arterial remodeling, which in turn results in elevated pulmonary arterial pressure (PAP) and subsequent right ventricular heart failure, eventually leading to premature death. However, there is still a lack of a diagnostic blood-based biomarker and therapeutic target for PH. Because of the difficulty of diagnosis, new and more easily accessible prevention and treatment strategy are being explored. New target and diagnosis biomarkers should also allow for early diagnosis. In biology, miRNAs are short endogenous RNA molecules that are not coding. It is known that miRNAs can regulate gene expression and affect a variety of biological processes. Besides, miRNAs have been proven to be a crucial factor in PH pathogenesis. miRNAs have various effects on pulmonary vascular remodeling and are expressed differentially in various pulmonary vascular cells. Nowadays, it has been shown to be critical in the functions of different miRNAs in the pathogenesis of PH. Therefore, clarifying the mechanism of miRNAs regulating pulmonary vascular remodeling is of great importance to explore new therapeutic targets of PH and improve the survival qualify and time of patients. This review is focused on the role, mechanism, and potential therapeutic targets of miRNAs in PH and puts forward possible clinical treatment strategies.

Establishment of a simplified score for predicting risk during intrahospital transport of critical patients: A prospective cohort study.

AIMS AND OBJECTIVES: To establish a simple score that enables nurses to quickly, conveniently and accurately identify patients whose condition may change during intrahospital transport. BACKGROUND: Critically ill patients may experience various complications during intrahospital transport; therefore, it is important to predict their risk before they leave the emergency department. The existing scoring systems were not developed for this population. DESIGN: A prospective cohort study. METHODS: This study used convenience sampling and continuous enrolment from 1 January, 2019, to 30 June, 2021, and 584 critically ill patients were included. The collected data included vital signs and any condition change during transfer. The STROBE checklist was used. RESULTS: The median age of the modelling group was 74 (62, 83) years; 93 (19.7%) patients were included in the changed group, and 379 (80.3%) were included in the stable group. The five independent model variables (respiration, pulse, oxygen saturation, systolic pressure and consciousness) were statistically significant (p < .05). The above model was simplified based on beta coefficient values, and each variable was assigned 1 point, for a total score of 0-5 points. The AUC of the simplified score in the modelling group was 0.724 (95% CI: 0.682-0.764); the AUC of the simplified score in the validation group (112 patients) was 0.657 (95% CI: 0.566-0.741). CONCLUSIONS: This study preliminarily established a simplified scoring system for the prediction of risk during intrahospital transport from the emergency department to the intensive care unit. It provides emergency nursing staff with a simple assessment tool to quickly, conveniently and accurately identify a patient's transport risk. RELEVANCE TO CLINICAL PRACTICE: This study suggested the importance of strengthening the evaluation of the status of critical patients before intrahospital transport, and a simple score was formed to guide emergency department nurses in evaluating patients.

A gene chip study suggests that miR-17-3p is associated with diabetic foot ulcers.

Background of the Study Diabetic foot ulcers (DFUs) are severe effect of diabetes. This research aimed to discover the role of micro-ribonucleic acid (miRNA) in treating DFUs involved in maggot debridement therapy (MDT) via a miRNA chip study. A miRNA chip approach was adopted. Patients with diabetes (type 1 or 2) who had at least one-foot ulcer (current or previous) were enrolled in the study. The alterations of miRNA expressions in the granulation tissue during treatment with MDT were measured. Following MDT, the increased expression of miR17-92 was verified in vivo. The miR-17-3p expression increased, and Flk-1 (vascular endothelial growth factor) expression was significantly reduced in patients with DFUs who received MDT (P < 0.01). Results from human umbilical vein endothelial cells that excrete or secrete showed consistency with in vitro findings (P < 0.001, P < 0.05). The overexpression of miR-17-3p demonstrated inhibitory activity on tube formation (P < 0.05). When DFUs were treated with MDT, it revealed that miR-17-3p had a negative regulatory effect on Flk-1.

Maggot debridement therapy stimulates wound healing by altering macrophage activation.

The purpose of this study is to determine the impact of maggot debridement therapy (MDT) on macrophages during the healing process of diabetic foot ulcers (DFU). The activation phenotype of macrophages during wound healing following MDT was evaluated using double staining immunohistochemistry (IHC). In addition, markers associated with macrophage activation were discovered using immunoblotting and real-time polymerase chain reaction (PCR). During the process of diabetic wound healing following MDT, the presence and over-expression of M2 macrophages were observed, while the under-expression of M1 macrophages was noted. In addition, the activation markers of macrophages exhibited a correlation with the indicated Th1/Th2 cytokines. MDT interventions have the potential to modulate macrophage activity, thereby aiding in the healing of diabetic foot wounds.

Mammalian Target of Rapamycin as the Therapeutic Target of Vascular Proliferative Diseases: Past, Present, and Future.

ABSTRACT: The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key pathological characteristic of vascular proliferative diseases. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays an important role in regulating cell growth, motility, proliferation, and survival, as well as gene expression in response to hypoxia, growth factors, and nutrients. Increasing evidence shows that mTOR also regulates VSMC proliferation in vascular proliferative diseases and that mTOR inhibitors, such as rapamycin, effectively restrain VSMC proliferation. However, the molecular mechanisms linking mTOR to vascular proliferative diseases remain elusive. In our review, we summarize the key roles of the mTOR and the recent discoveries in vascular proliferative diseases, focusing on the therapeutic potential of mTOR inhibitors to target the mTOR signaling pathway for the treatment of vascular proliferative diseases. In this study, we discuss mTOR inhibitors as promising candidates to prevent VSMC-associated vascular proliferative diseases.

Relationship between family support, serum lipid knowledge and quality of life in Chinese breast cancer women with adjuvant endocrine therapy.

BACKGROUND: Serum lipid management is an important health management goal for breast cancer patients with endocrine therapy, and serum lipid knowledge is a substantial factor influencing patients' serum lipid management behavior. The aim of this study was to explore the relationship between family support, serum lipid knowledge and quality of life in breast cancer women with endocrine therapy. METHODS: Through convenience sampling, 301 women who had been treated in the First Affiliated Hospital of China Medical University and Liaoning Cancer Hospital were selected to fill in the questionnaire of knowledge-attitude-practice (KAP) on serum lipids, family support questionnaire (FSQ), and the functional assessment of cancer therapy-breast cancer (FACT-B). Pearson correlation coefficient was used to analyze the correlation between the three. Multiple linear regression model was used to analyze the influencing factors of quality of life in breast cancer patients with endocrine therapy. RESULTS: The average score of KAP on serum lipids was 42.62 ± 7.333, the average score of family support was 12.55 ± 2.390, and the average score of quality of life was 97.13 ± 21.347, all above the medium level. Family support of breast cancer women with endocrine therapy was positively correlated with serum lipid knowledge and quality of life. Disease stage, family support, and serum lipid knowledge were the influencing factors of quality of life of breast cancer women with endocrine therapy. CONCLUSION: Good family support is associated with better serum lipid knowledge in breast cancer women with endocrine therapy. Therefore, interventions that aim to improve the level of family support may be one way to improve the knowledge level of serum lipid, prevent cardiovascular and cerebrovascular diseases, and improve the quality of life.

Demand preferences for health management services in a population of older adults with visual impairment in China: a conjoint analysis.

BACKGROUND: Visual impairment (VI) seriously affects the quality of life of the older adults. It is important to formulate appropriate health management strategies for the older adults with VI to help delay the disease development and progression, and improve life quality. The aim of this study was to understand the demand preference for health management services of the older adults with VI, and to provide a reference for the development of future health management strategies in this population. METHODS: The conjoint analysis method was used to analyze demand preferences for health management services of the older adults with VI. 11 keywords were extracted after literature analyzed, 6 keywords were selected as the attributes of health management strategy after expert discussion and the level of each attribute was determined. Then 18 representative virtual health management strategies were formed by combination of different attribute levels through orthogonal design, and older adults with VI were asked to score. A total of 334 older adults with VI who attended the ophthalmology department of the First Affiliated Hospital of China Medical University and the Fourth People's Hospital of Shenyang from February 27, 2021 to June 30, 2021were enrolled in this study by stratified sampling. Of the 334 included people, 80 had grade 1 VI, 80 had grade 2 VI, 84 had grade 3 VI, and 90 had grade 4 VI. RESULTS: The relative importance of health management services ranked by older adults with VI was continuing care (24.033%), visual aid application (19.61%), health education (16.241%), preventive healthcare (15.667%), safety management (12.757%), and rehabilitation training (11.392%). The utility values of each level of continuing care, safety management and preventive healthcare were positive, whereas the utility values of each level of visual aid application, health education and rehabilitation training were negative. The relative importance and utility values of health management services were different for the older adults with different grades of VI. CONCLUSIONS: From the whole group, the older adults with VI have a higher preference for continuing care and a lower preference for rehabilitation training. The preference of the older adults with different grades of VI is different, so medical workers can formulate corresponding health management strategies according to their different demand preferences, and carry out hierarchical health management. Services that they preferred should be satisfied as much as possible in the health management strategy, while the reasons for the services with lower preference can be explored and make targeted improvement to meet the demand preferences of them.

Survey of the demand for care services for older people and the training needs of their care workers: a cross-sectional study in Northeast China.

BACKGROUND: The older population is increasingly utilizing professional healthcare services, while the requirements for caregivers are becoming more demanding. Therefore, it is important to be mindful not only of the service needs of older people but also to consider the training needs of their care workers. The present study aimed to investigate the care service needs for older people and the training needs of their care workers. METHODS: A cross-sectional questionnaire was used to survey 589 residents of 6 nursing homes and 2 geriatric hospitals, 415 medical staff from 7 geriatric hospitals, 5 nursing homes, and 1 community institution, and 372 nursing assistants from 21 nursing institutions in northeast China. RESULTS: The service with the greatest demand and that with which users were most satisfied was regular visits by healthcare personnel, which was the case for 87.27% of the care recipients. Of the medical staff, 75.42% had training needs related to geriatric healthcare, while the most requested training content was the comprehensive assessment of old people. The most requested method for the delivery of training was by self-study online video courses. Of nursing assistants, only 53.4% had obtained the relevant practicing certificate. While 83.6% participated in relevant training, 86% expressed the need for additional training. The majority of this category of staff wished to receive training in everyday care routines, and the majority wanted to learn by way of practical training. CONCLUSIONS: The care needs of the older population are diverse, and the work performed by healthcare personnel is increasing in scope. The existing training system for such care personnel is not perfect, and the demand for training is high. Existing training methods and content require improvement.

[Factors Affecting the Surgical Level of Major Amputations in Patients with Severe Diabetic Foot].

Objective: To investigate the main factors affecting the surgical level of major amputations in patients with severe diabetic foot. Methods: A case-control study was conducted to analyze the clinical data of severe diabetic foot patients who had major amputations and were admitted to the Intensive Care Unit (ICU), Air Force Hospital of PLA Eastern Theater Command between July 2020 and July 2022. According to their surgical level of amputation, patients were divided into transtibial amputation (TT) group and transfemoral amputation (TF) group. Correlation analysis was performed with the clinical data of the patients, and multivariate logistic regression was performed to screen for relevant factors affecting the surgical level of major amputation. Results: The data of 48 patients with major amputations were collected, including 15 patients in the TT group and 33 patients in the TF group. The proportion of patients who had cardiovascular and cerebrovascular complications in the TT group was lower than that in the TF group (26.67% [4/15] vs. 57.58% [19/33], P<0.05), the proportion of patients who had lower extremity arterial intervention history was higher in the TT group than that in the TF group (40% [6/15] vs. 9.09% [3/33], P<0.05), and the proportion of patients who had elevated creatinine level was lower in the TT group than that in the TF group (70.31±22.98 vs. 127.98±108.38, P<0.05). Moreover, the history of lower extremity arterial intervention may be an independent protective factor for determining the surgical level of major amputations (odds ratio [ OR]=0.15, 95% confidence interval [ CI]: 0.03-0.72, P=0.018). Conclusion: History of cardiovascular and cerebrovascular diseases, serum creatinine level and history of lower extremity arterial intervention are the main factors affecting the surgical level of major amputations in patients with severe diabetic foot, and the history of lower extremity arterial intervention may be an independent protective factor.

Genome-wide identification and transcriptional characterization of DNA methyltransferases conferring temperature-sensitive male sterility in wheat.

BACKGROUND: DNA methyltransferase (DMT) genes contribute to plant stress responses and development by de novo establishment and subsequent maintenance of DNA methylation during replication. The photoperiod and/or temperature-sensitive genic male sterile (P/TGMS) lines play an important role in hybrid seed production of wheat. However, only a few studies have reported on the effect of DMT genes on temperature-sensitive male sterility of wheat. Although DMT genes have been investigated in some plant species, the identification and analysis of DMT genes in wheat (Triticum aestivum L.) based on genome-wide levels have not been reported. RESULTS: In this study, a detailed overview of phylogeny of 52 wheat DMT (TaDMT) genes was presented. Homoeolog retention for TaDMT genes was significantly above the average retention rate for whole-wheat genes, indicating the functional importance of many DMT homoeologs. We found that the strikingly high number of TaDMT genes resulted mainly from the significant expansion of the TaDRM subfamily. Intriguingly, all 5 paralogs belonged to the wheat DRM subfamily, and we speculated that tandem duplications might play a crucial role in the TaDRM subfamily expansion. Through the transcriptional analysis of TaDMT genes in a TGMS line BS366 and its hybrids with the other six fertile lines under sterile and fertile conditions, we concluded that TaCMT-D2, TaMET1-B1, and TaDRM-U6 might be involved in male sterility in BS366. Furthermore, a correlation analysis showed that TaMET1-B1 might negatively regulate the expression of TaRAFTIN1A, an important gene for pollen development, so we speculated regarding an epigenetic regulatory mechanism underlying the male sterility of BS366 via the interaction between TaMET1-B1 and TaRAFTIN1A. CONCLUSIONS: Our findings presented a detailed phylogenic overview of the DMT genes and could provide novel insights into the effects of DMT genes on TGMS wheat.

Development and Evaluation of the Psychosocial Adaptation Questionnaire among Patients with Chronic Skin Disease.

BACKGROUND/OBJECTIVE: Chronic skin disease (CSD) often has physiological, psychological, and social impacts, which requires the patient to adjust to achieve psychosocial adaptation (PSA). As a standardized assessment instrument was lacking, we developed a PSA questionnaire for patients with CSD (PSAQ-CSD). METHODS: According to the steps of questionnaire development, a systematic process of scoping review, qualitative research, content validity expert review, testing in a sample of 321 adults, item analysis, and classical test theory methods were applied. RESULTS: Following item analysis and exploratory factor analyses, 18 items were eventually entered into the model of confirmatory factor analyses, with a cumulative contribution of 65.435%. Three subscales were developed: emotional, self-cognitive, and social dimensions. Item analysis, exploratory factor analyses, and content validity expert review narrowed the subscales to 8, 6, and 4 items, respectively. CONCLUSIONS: The 18-item PSAQ-CSD has been confirmed to have good internal consistency reliability and convergent and discriminant validity. It may be a useful tool to evaluate the PSA among patients with CSD and provide a basis for further research.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

CXCL2, a new critical factor and therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Previous studies have shown that inflammatory chemokines are involved in the physiological functions of cytoskeletal reorganization, cell migration, adhesion and immune responses. However, in the past decade, there have been studies showing that inflammatory chemokines play a key role in CVD. Importantly, CXC motif chemokine ligand 2 (CXCL2) has been shown to be involved in the pathogenesis of cardiovascular disease. CXCL2 exerts its effects on the cardiovascular system by mediating inflammatory responses, but the specific signaling pathways by which CXCL2 exerts its effects in CVD remain unknown and need to be further investigated. This review aims to investigate the expression changes of CXCL2 in acute myocardial infarction (AMI), atherosclerosis (AS), obesity, diabetes and ischemic stroke (IS) and its potential key role in cardiovascular disease in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Factors influencing medication-taking behaviour with adjuvant endocrine therapy in women with breast cancer: A qualitative systematic review.

AIMS: To explore the experience and feelings associated with the endocrine therapy treatment trajectory in women with breast cancer and what affects medication taking behaviour. DESIGN: Qualitative systematic review. DATA SOURCES: Qualitative studies were extracted from PubMed, EMBASE, CINAHL, PsycINFO from inception of each database until February 2019. REVIEW METHODS: The systematic search method SPIDER (sample, phenomenon of interest, design, evaluation, research type) was used. Thematic synthesis of the qualitative data was used. RESULTS: A total of 478 were identified in the initial search. Only 17 articles met inclusion criteria and were included in this review. Five analytical themes and 17 descriptive subthemes were identified. CONCLUSIONS: The systematic review highlights knowledge, balancing the scales, self-efficacy and support influence medication taking behaviour to women with breast cancer. IMPACT: The medication taking behaviour of breast cancer women can be classified into four types: acceptance/persistence, bearing/suffering, hesitation/adjustment, refusing/abandoning. The four types can switch from one to another. Medication taking behaviour is affected by knowledge, balancing the scales, self-efficacy, and support. The medical institutions, communities, and families can gain knowledge of the treatment experiences of women to better understand medication taking behaviour and those at risk for non-adherence. Women wanted different types and amounts of information. Healthcare providers should be aware of patient preferences and take targeted interventions to help them receive treatment.

[Vasovagal syncope or postural orthostatic tachycardia syndrome in children with neurological symptoms at disease onset: a clinical analysis of 88 cases].

OBJECTIVE: To study the clinical features of vasovagal syncope (VVS) and postural orthostatic tachycardia syndrome (POTS) in children with neurological symptoms at disease onset. METHODS: A retrospective analysis was performed on the medical data of 88 children with the initial symptoms of the nervous system, such as transient loss of consciousness, dizziness, headache, and convulsion, who were finally diagnosed with VVS or POTS. RESULTS: Of the 88 children, there were 35 boys (40%) and 53 girls (60%), with an age of 4-15 years. The peak age of onset was between 10 and 13 years. All the children had the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. Nervous system diseases were excluded by electroencephalography, cerebrospinal fluid examination, and cranial MRI. Of the 88 children, 53 (60%) were confirmed with VVS, and 35 (40%) with POTS, according to the results of head-up tilt test (HUTT). Five children with the initial symptom of transient loss of consciousness were misdiagnosed with epilepsy. Predisposing factors were determined for 59 children (67%), and prolonged standing was the most common factor, followed by change in body position and strenuous exercise. Premonitory symptoms were observed in 66 children (75%), among which chest discomfort was the most common symptom, followed by gastrointestinal symptoms (nausea, vomiting, and abdominal pain) and pale complexion. All 88 children received health education and exercise for autonomic nerve function, among whom 53 children with VVS were given oral rehydration salts and 35 children with POTS were given oral rehydration salts and metoprolol. All 88 children were followed up for 18 months, and the response rates to the above treatment at 3, 6, 12, and 18 months of follow-up were 87%, 93%, 93%, and 90% respectively. CONCLUSIONS: In addition to nervous system diseases, functional cardiovascular diseases including VVS and POTS should be considered for children with the initial symptoms of transient loss of consciousness, dizziness, headache, and convulsion. HUTT can be used to make a confirmed diagnosis, and the early treatment can achieve a good outcome.

Oxymatrine ameliorates insulin resistance in rats with type 2 diabetes by regulating the expression of KSRP, PETN, and AKT in the liver.

Insulin resistance plays a key role in the development and progression of type 2 diabetes mellitus (T2DM). Recent studies found that insulin resistance was associated with the dysfunction of KH-type splicing regulatory protein (KSRP) expression and AKT pathway, and that oxymatrine possesses an antidiabetic effect. The aim of the present study was to investigate whether the protection of oxymatrine against T2DM was associated with the modulation of the KSRP expression and AKT pathway. Sprague-Dawley rats were fed a high-fat diet and injected with streptozotocin intraperitoneally to induce T2DM, which led to an increase in blood glucose levels and insulin resistance, and a decrease in insulin sensitivity and glycogen synthesis concomitant with KSRP downregulation, PTEN upregulation, and AKT phosphorylation deficiency. The administration of oxymatrine decreased blood glucose levels and insulin resistance, increased insulin sensitivity, and improved glycogen synthesis in the liver of T2DM rats, through a reversal in the expression of KSRP, PTEN, and AKT. On the basis of these observations, we concluded that oxymatrine can protect T2DM rats from insulin resistance through the regulation of the KSRP, PETN, and AKT expression in the liver.

Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway.

Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed significantly increased proliferation and differentiation. We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products, i.e., IL-1 family members such as IL-1ß and IL-18 were upregulated in the PVAT of obese mini pigs; PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid. Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.

Comparative toxicity and toxicokinetic studies of oxiracetam and (S)-oxiracetam in dogs.

Oxiracetam (ORT) is known as a derivative of piracetam in the family of nootropics for treating memory impairment and cognition disorders. Given the chiral toxicological concerns surrounding ORT and the absence studies of (S)-ORT, the toxicity and toxicokinetics of (S)-ORT, and comparative toxicology of oxiracetam were systematically investigated in dogs following acute and 13-week repeated oral dosing. The animal toxicity mainly manifested as loose stools in both the acute and the 13-week studies. The no-observed-adverse-effect level is proposed to be 100 mg/kg. The 13-week toxicokinetics study indicated that, in the (S)-ORT group, the time to peak concentration was delayed, elimination half-life extended, and apparent volume of distribution increased compared with the ORT group. The clearance rate increased at low- and mid-doses, but decreased in the high-dose group and was accompanied by drug accumulation. Compared with the same dose of ORT, (S)-ORT had a lower clearance rate and longer elimination half-life.