RESUMEN
BACKGROUND: Joint contracture is a common clinical problem affecting joint function. Capsule fibrosis plays a pivotal role in the progression of Joint contracture. Previous studies have reported that autophagy plays a regulatory role in visceral fibrosis. OBJECTIVE: This study aimed to investigate whether extracorporeal shock wave therapy (ESWT) and melatonin alleviate joint capsule fibrosis in rats with extended knee joint contracture by regulating autophagy. METHODS: A rat knee joint extension contracture model was made. Then, the rats were treated with ESWT, melatonin, ESWT + melatonin, or ESWT + melatonin + mTOR agonist for 4 weeks. The range of motion (ROM) of the knee joints was measured. Joint capsules were collected and observed for pathological changes by H&E and Masson staining. LC3B protein expression was evaluated by immunofluorescence staining. TGF-ß1, MMP-1, Col-â , Col-â ¢, LC3, ATG7, Beclin1, p-AMPK, p-mTOR and p-ULK1 protein expressions were measured by Western blot assay. RESULTS: The intervention groups had significantly improved ROM of knee joint (P < 0.05), significantly improved pathological changes on HE and Masson staining, significantly decreased protein expressions of TGF-ß1, MMP-1, Col-â , Col-â ¢ and pmTOR (P < 0.05), and significantly increased protein expressions of LC3B, LC3II/LC3I ratio, ATG7, Beclin1, p-AMPK, and p-ULK1 (P < 0.05). Among these groups, the effects demonstrated by the ESWT + melatonin group were the best. With the mTOR agonist supplement, the therapeutic effects of extracorporeal shock waves and melatonin were significantly reduced. CONCLUSION: ESWT plus melatonin alleviated knee joint capsule fibrosis in rats by regulating autophagy.
RESUMEN
OBJECTIVES: Concordance of preferences for end-of-life care regarding patients between patients with advanced cancer and family caregivers can improve the likelihood of honoring dying patients' wishes. However, there is a dearth of knowledge in mainland China. The purpose of this study was to examine patient-family caregiver concordance about patients' life-sustaining treatment preferences and associated factors among patients with advanced cancer in China. METHODS: From September 2019 to December 2021, a convenience sample of 406 dyads of advanced cancer patient-family caregiver were recruited from 2 tertiary hospitals in Wuhan, China. Participants completed a questionnaire about patient's preferences for life-sustaining treatment, respectively. The concordance was assessed by percent agreement and kappa coefficients. Associated factors were identified by univariate analysis and binary logistic regression. RESULTS: The average concordance rate on the preferences for life-sustaining treatment was 56.1%, ranging from 52.9% to 59.3%. Factors associated with a higher level of patient-family caregiver concordance were following: patients who were married, whose educational levels were at college or above, who had not been informed of diagnosis by a physician, who had been informed of the effects and side effects of related drugs by a physician, and who cared for a seriously ill family member or friend and caregivers whose educational level were primary or below. CONCLUSIONS: The patient-family caregiver concordance about patients' life-sustaining treatment preferences among patients with advanced cancer was poor. Patients' and caregivers' understanding of life-sustaining treatment and its efficacy in end-of-life should be facilitated. Relevant conversation should be encouraged between patients and caregivers, thus providing value-concordant end-of-life care for patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Health professionals need to carry out advanced care planning in oncology departments on mainland China to encourage patients and caregivers to discuss patients' end-of-life care preferences. Facilitating patients' and caregivers' understanding of life-sustaining treatment preferences may help improve the patient-caregiver concordance on life-sustaining treatment preferences among patients with advanced cancer.
Asunto(s)
Cuidadores , Neoplasias , Prioridad del Paciente , Cuidado Terminal , Humanos , Masculino , Femenino , Neoplasias/psicología , Neoplasias/enfermería , Neoplasias/terapia , Persona de Mediana Edad , Estudios Transversales , China , Cuidadores/psicología , Anciano , Cuidado Terminal/psicología , Encuestas y Cuestionarios , Adulto , Cuidados para Prolongación de la Vida , Anciano de 80 o más AñosRESUMEN
Curcumae rhizoma (CR) is the dried rhizoma of Curcuma phaeocaulis Val (CP), Curcuma kwangsiensis S. G. Lee et C. F. Liang (CK) and Curcuma wenyujin Y. H. Chen et C. Ling (CW), used widely to treat blood stagnation in China. Currently, quality control indicators for CR are limited to chemical composition analysis. It is unclear whether the current quality standard of the multicomponent content of CR can reflect clinical effects, due to the lack of the evaluation of biological effects. A method of evaluating quality was developed called the effect-constituent index (ECI). By meticulously measuring and calibrating the key active components, the ECI offers a comprehensive assessment of the CR's biological effects, establishing a crucial link to clinical efficacy and safety. An analytical protocol employing high-performance liquid chromatography (HPLC) was devised to ascertain the presence and measure ten principal constituents within CR sourced from various species and the content of total volatile oil was also measured. An In vitro antiplatelet aggregation assay was developed to measure the antiplatelet aggregation biopotencies of thirty batches of CR and ten main components. Then, the calibration weights for each constituent in the ECI were determined based on the antiplatelet aggregation biopotency values of eight components with notable efficacy. The ECI calculation involved summing the products obtained by multiplying the content (Ci) of each component by its corresponding biopotency weight (Wi). Correlation analysis unveiled a the most robust correlation (R = 0.8579, p < 0.001) between ECI and antiplatelet aggregation biopotency of CR, when compared to individual components or volatile oil content. The devised ECI, synthesizing chemical and biological data pertinent to clinical effectiveness, facilitates a nuanced assessment of CR quality across various species in its efficacy in treating blood stagnation. This method addresses the challenge of guaranteeing effectiveness through chemical analysis alone. This study offers substantiation for the applicability of the ECI as a tool for assessing the quality of traditional Chinese medicine (TCM).
Asunto(s)
Curcuma , Medicamentos Herbarios Chinos , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria , Rizoma , Curcuma/química , Rizoma/química , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta Presión , Control de Calidad , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Animales , HumanosRESUMEN
PURPOSE: Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. METHODS: Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group's knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, ß-catenin protein expression in joint capsule using Western blotting. RESULTS: Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, ß-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, ß-catenin protein expression were decreased. CONCLUSIONS: Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.
RESUMEN
BACKGROUND: Klebsiella pneumoniae is the most commonly encountered pathogen in clinical practice. Widespread use of broad-spectrum antibiotics has led to the current global dissemination of carbapenem-resistant K. pneumoniae, which poses a significant threat to antibacterial treatment efficacy and public health. Outer membrane vesicles (OMVs) have been identified as carriers capable of facilitating the transfer of virulence and resistance genes. However, the role of OMVs in carbapenem-resistant K. pneumoniae under external pressures such as antibiotic and phage treatments remains unclear. METHODS: To isolate and purify OMVs under the pressure of phages and tigecycline, we subjected K. pneumoniae 0692 harboring plasmid-mediated blaNDM-1 and blaKPC-2 genes to density gradient separation. The double-layer plate method was used to isolate MJ1, which efficiently lysed K. pneumoniae 0692 cells. Transmission electron microscopy (TEM) was used to characterize the isolated phages and extract OMV groups for relevant morphological identification. Determination of protein content of each OMV group was conducted through bicinchoninic acid assay (BCA) and proteomic analysis. RESULTS: K. pneumoniae 0692 released OMVs in response to different environmental stimuli, which were characterized through TEM as having the typical structure and particle size of OMVs. Phage or tigecycline treatment alone resulted in a slight increase in the mean protein concentration of OMVs secreted by K. pneumoniae 0692 compared to that in the untreated group. However, when phage treatment was combined with tigecycline, there was a significant reduction in the average protein concentration of OMVs compared to tigecycline treatment alone. Proteomics showed that OMVs encapsulated numerous functional proteins and that under different external stresses of phages and tigecycline, the proteins carried by K. pneumoniae 0692-derived OMVs were significantly upregulated or downregulated compared with those in the untreated group. CONCLUSIONS: This study confirmed the ability of OMVs to carry abundant proteins and highlighted the important role of OMV-associated proteins in bacterial responses to phages and tigecycline, representing an important advancement in microbial resistance research.
Asunto(s)
Antibacterianos , Bacteriófagos , Carbapenémicos , Klebsiella pneumoniae , Proteómica , Tigeciclina , Tigeciclina/farmacología , Klebsiella pneumoniae/virología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Bacteriófagos/genética , Bacteriófagos/fisiología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Humanos , Vesículas Extracelulares/metabolismo , Membrana Externa Bacteriana/metabolismo , Membrana Externa Bacteriana/efectos de los fármacos , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Plásmidos/genética , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
BACKGROUND: Individuals who suffer from simple snoring rarely go to a doctor due to a lack of medical knowledge, but simple snoring can reduce the individual's quality of life and may cause social problems to the bed partner/family members. OBJECTIVES: The aims of the present study are to explore the effects of online modified oropharyngeal exercises on the individuals with simple snoring and to provide a rehabilitation method for individuals with simple snoring. METHODS: This study is a double-blinded, two-arm, randomized controlled trial. Participants were enrolled and randomly assigned to the intervention group (n = 33) or the control group (n = 33). The participants in the control group received health education on snoring, while the participants in the intervention group received the modified oropharyngeal exercise besides health education on snoring. The intervention duration was 4 weeks. The primary outcomes included snoring index, snoring loudness, and snoring quantity. The secondary outcomes included self-reported snoring, sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life. All outcomes were measured at baseline, 4 weeks, and 8 weeks. RESULTS: Generalized estimating equations (GEE) analyses showed significant differences between the intervention group and the control group on snoring index, loudness, and quantity (p < .001). Moreover, modified oropharyngeal exercise had effects on sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life in individuals with simple snoring (p < .001). Self-reported snoring also improved at 8 weeks. CONCLUSION: The modified oropharyngeal exercises were effective in improving simple snoring. It could also improve sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life.
RESUMEN
DNAJA1 is a member of type I DnaJ proteins, which is essential for spermatogenesis and male fertility. However, its expression pattern in the testes and its impact on spermatogenesis remains unclear. Our study aimed to elucidate the mechanism of action of DNAJA1. We employed DNAJA1 knockout mice in this study. Western blotting and immunofluorescence analysis were conducted to determine the protein abundance of DNAJA1 in testes at various developmental stages. Our results revealed that DNAJA1 is predominantly expressed in the testes, and its knockout leads to complete infertility in male mice. We observed that DNAJA1 protein levels increased on postnatal days 14, 21, and 28, peaking on postnatal day 35 in mice. Immunofluorescence staining indicated that DNAJA1 expression varies across different stages of the spermatogenesis cycle. Additionally, DNAJA1 was absent in epididymal sperm. In early- and mid-stage tubules, DNAJA1 protein distribution was co-localized with residual bodies in elongating spermatids. Furthermore, we found that DNAJA1 knockout significantly reduced protein polyubiquitination in the testis. Analysis of the GEO database showed that DNAJA1 levels were significantly decreased in semen samples from subjects with teratozoospermia, asthenozoospermia, and impaired spermatogenesis. Our findings suggest that DNAJA1 is an essential protein for spermatogenesis, and its deletion reduces protein polyubiquitination in the testis, ultimately resulting in infertility and spermatogenesis defects.
RESUMEN
Despite the considerable potential of immune checkpoint blockade (ICB) therapy in treating various cancer types, it faces several challenges, of which the constrained objective response rate and relatively short duration of response observed in patients with cancer are the most important. This study introduces an injectable temperature-sensitive hydrogel, Pluronic F-127 (PF-127)@MnCl2/ alginate microspheres (ALG-MS)@MgCl2, that enhances the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) in cancer cells. The hydrogel material used in this study facilitated the rapid release of a significant amount of manganese ions (Mn2+) and the gradual and sustained release of magnesium ions (Mg2+) within the tumor microenvironment. This staged release profile promotes an immune microenvironment conducive to the cytotoxicity of CD8+ T cells and natural killer cells, thereby enhancing the efficacy of ICB therapy. Furthermore, the PF-127@MnCl2/ALG-MS@MgCl2 composite hydrogel exhibits the ability to convert drug-resistant tumor ("cold tumor") with a low PD-L1 response to a "hot tumor" with a high PD-L1 response. In summary, the PF-127@MnCl2/ALG-MS@MgCl2 hydrogel manipulates the immune microenvironment through the precise discharge of Mg2+ and Mn2+, thus, augmenting the efficacy of ICB therapy.
Asunto(s)
Alginatos , Preparaciones de Acción Retardada , Hidrogeles , Inmunoterapia , Magnesio , Manganeso , Microesferas , Neoplasias , Poloxámero , Microambiente Tumoral , Hidrogeles/química , Hidrogeles/administración & dosificación , Animales , Inmunoterapia/métodos , Magnesio/química , Magnesio/administración & dosificación , Microambiente Tumoral/efectos de los fármacos , Manganeso/química , Manganeso/administración & dosificación , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/inmunología , Poloxámero/química , Alginatos/química , Línea Celular Tumoral , Compuestos de Manganeso/química , Compuestos de Manganeso/administración & dosificación , Femenino , Cloruros/química , Ratones Endogámicos C57BL , Antígeno B7-H1 , Ratones , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacosRESUMEN
BACKGROUND: Microsatellite instability (MSI) caused by DNA mismatch repair (MMR) deficiency is of great significance in the occurrence, diagnosis and treatment of colorectal cancer (CRC). AIM: This study aimed to analyze the relationship between mismatch repair status and clinical characteristics of CRC. METHODS: The histopathological results and clinical characteristics of 2029 patients who suffered from CRC and underwent surgery at two centers from 2018 to 2020 were determined. After screening the importance of clinical characteristics through machine learning algorithms, the patients were divided into deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) groups based on the immunohistochemistry results and the clinical feature data between the two groups were observed by statistical methods. RESULTS: The dMMR and pMMR groups had significant differences in histologic type, TNM stage, maximum tumor diameter, lymph node metastasis, differentiation grade, gross appearance, and vascular invasion. There were significant differences between the MLH1 groups in age, histologic type, TNM stage, lymph node metastasis, tumor location, and depth of invasion. The MSH2 groups were significantly different in age. The MSH6 groups had significant differences in age, histologic type, and TNM stage. There were significant differences between the PMS2 groups in lymph node metastasis and tumor location. CRC was dominated by MLH1 and PMS2 combined expression loss (41.77%). There was a positive correlation between MLH1 and MSH2 and between MSH6 and PMS2 as well. CONCLUSIONS: The proportion of mucinous adenocarcinoma, protruding type, and poor differentiation is relatively high in dMMR CRCs, but lymph node metastasis is rare. It is worth noting that the expression of MMR protein has different prognostic significance in different stages of CRC disease.
Asunto(s)
Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Estadificación de Neoplasias , Inestabilidad de Microsatélites , Metástasis Linfática , AdultoRESUMEN
BACKGROUND: Maintaining the vitality and functionality of dental pulp is paramount for tooth integrity, longevity, and homeostasis. Aiming to treat irreversible pulpitis and necrosis, there has been a paradigm shift from conventional root canal treatment towards regenerative endodontic therapy. AIM OF REVIEW: This extensive and multipart review presents crucial laboratory and practical issues related to pulp-dentin complex regeneration aimed towards advancing clinical translation of regenerative endodontic therapy and enhancing human life quality. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this multipart review paper, we first present a panorama of emerging potential tissue engineering strategies for pulp-dentin complex regeneration from cell transplantation and cell homing perspectives, emphasizing the critical regenerative components of stem cells, biomaterials, and conducive microenvironments. Then, this review provides details about current clinically practiced pulp regenerative/reparative approaches, including direct pulp capping and root revascularization, with a specific focus on the remaining hurdles and bright prospects in developing such therapies. Next, special attention was devoted to discussing the innovative biomimetic perspectives opened in establishing functional tissues by employing exosomes and cell aggregates, which will benefit the clinical translation of dental pulp engineering protocols. Finally, we summarize careful consideration that should be given to basic research and clinical applications of regenerative endodontics. In particular, this review article highlights significant challenges associated with residual infection and inflammation and identifies future insightful directions in creating antibacterial and immunomodulatory microenvironments so that clinicians and researchers can comprehensively understand crucial clinical aspects of regenerative endodontic procedures.
RESUMEN
Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3ß/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.
Asunto(s)
Nanopartículas , Estrés Oxidativo , Periodontitis , Estrés Oxidativo/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Periodontitis/patología , Nanopartículas/química , Humanos , Animales , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Minociclina/farmacología , Minociclina/química , Minociclina/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Antibacterianos/química , Antibacterianos/farmacología , Lipopolisacáridos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Especies Reactivas de Oxígeno/metabolismo , ImidazolesRESUMEN
Despite numerous studies have explored the association between sleep duration and cognition, the link between sleep duration trajectories and cognition remains underexplored. This systematic review aims to elucidate this correlation. We analyzed 55 studies from 14 countries, comprising 36 studies focusing on sleep duration, 20 on insomnia, and 13 on hypersomnia. A total of 10,767,085 participants were included in 49 cohort studies with a mean follow-up duration of 9.1 years. A non-linear association between sleep duration and cognitive decline was identified. Both long (risk ratio (RR):1.35, 95â¯% confidence intervals (CIs):1.23-1.48) and short sleep durations (RR: 1.12, 95â¯% CIs:1.03-1.22) were associated with an elevated risk of cognitive decline compared to moderate sleep duration. Additionally, hypersomnia (RR:1.26, 95â¯% CIs: 1.15-1.39) and insomnia (RR: 1.16, 95â¯% CIs: 1.002-1.34) were also linked to an increased risk. Moreover, prolonged sleep duration posed a higher risk of cognitive decline than stable sleep duration (RR:1.42, 95â¯% CIs:1.27-1.59). Importantly, transitioning from short or moderate to long sleep duration, as well as persistent long sleep duration, exhibited higher RRs for cognitive decline (RRs: 1.94, 1.40, and 1.28, respectively) compared to persistent moderate sleep duration. Our findings underscore the significance of prolonged sleep duration, alongside short and long sleep durations, with an elevated risk of cognitive decline. The association is tied to the degree of sleep duration changes. Our study highlights the importance of considering changes in sleep patterns over time, not just static sleep durations.
Asunto(s)
Disfunción Cognitiva , Duración del Sueño , Humanos , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Estudios de Cohortes , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/fisiopatología , Factores de TiempoRESUMEN
Objectives: Optimizing the pharmaceutical industrial structure is the key mission of China's healthcare reform. From the industrial structure perspective, this study empirically evaluated the impact of China's national volume-based procurement (NVBP) policy on market concentration in the hospital-end drug market. Methods: This study used drug procurement data of China's public medical institutions which obtained from the national database. A quasi-natural experiment was designed involving eleven pairs of matched treatment-control region combinations, with NVBP policy as the intervention measure. The market was defined by drug name (molecular boundary) and city/province (geographical boundary). Market changes were measured from three dimensions: the number of enterprises and products, market share, and Herfindahl-Hirschman index (HHI). Dual comparison approach and difference-in-difference (DID) method with fixed effect model were applied to quantify policy impacts. Results: The number of enterprises and products decreased by 18 and 83 in pilot regions after NVBP policy, far more than the decreases in control regions (6 and 21). The accumulative market share of 15 bid-winning enterprises increased by 53.67% in volume and 18.79% in value, among which the increment of enterprises with low baseline market share was more prominent (66.64% and 36.40%). Among three enterprise types, the market share of generic consistency evaluation (GCE) certificated generics significantly increased, GCE uncertificated generics significantly decreased, and originators slightly decreased. DID models indicated significantly positive impact of NVBP policy on market concentration, with HHI-volume and HHI-value increasing by 49.33% (ß = 0.401, p < 0.01) and 21.05% (ß = 0.191, p < 0.01). Conclusion: The implementation of NVBP promoted the intensive drug circulation and supply of Chinese public hospitals, intensifying the exit of GCE uncertificated generics from the hospital-end market. NVBP combined with GCE standards significantly improved market concentration, which brought a positive signal of pharmaceutical industrial structure optimization in China. In the future context of normalized and institutionalized NVBP, the balance should be further sought between low drug prices and reliable hospital drug supply, sustainable industry development.
RESUMEN
BACKGROUND: Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. METHODS: In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. RESULTS: The baPWV was linked with VFA, waist circumference, and women's SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men's SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05). CONCLUSIONS: Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.
RESUMEN
AIMS: To investigate the prevalence of anxiety and depression symptoms in intensive care unit (ICU) patients with cardiovascular disease (CVD) and to explore which elements are risk factors for the development of anxiety and depression symptoms. DESIGN: A cross-sectional study. METHODS: A total of 1028 ICU patients with CVD were enrolled in this cross-sectional study. Logistic regression was used to assess risk factors and associations between anxiety and depression symptoms, and mediation analysis was used to explore the effect of risk factors on the association between anxiety and depression symptoms. Reporting of the study followed the STROBE checklist. RESULTS: The results showed that among ICU patients with CVD, 38.1% had anxiety symptoms, 28.7% had depression symptoms and 19.3% had both anxiety and depression symptoms, and there was a significant association between anxiety and depression symptoms. We also identified female gender, hypertension, hyperlipidemia and cardiac function class IV as independent risk factors for anxiety and depression symptoms. Importantly, these factors also mediated the association between anxiety and depression symptoms, emphasising their role in the psychological well-being of this patient group. CONCLUSION: ICU patients with CVD were prone to anxiety and depression symptoms. Female gender, hypertension, hyperlipidemia and cardiac function class IV were identified as independent risk factors that also served as mediators in the relationship between anxiety and depression symptoms. Especially, cardiac function class IV emerged as a critical factor in this association. RELEVANCE TO CLINICAL PRACTICE: It is imperative for critical care professionals to recognize the elevated risk of depression and anxiety among ICU patients with severe CVD, especially those with cardiac function class IV, hypertension, hyperlipidemia and females. Proactive and supportive measures are essential for this vulnerable group during their ICU stay to safeguard their mental health and prevent negative outcomes. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
RESUMEN
For sperm cryopreservation, the conventional method, which requires glycerol, has been used for a long time. In addition, the permeable cryoprotectant-free vitrification method has been continuously studied. Although the differences of cryopreservation effects between the two methods have being studied, differences in microRNA (miRNA) profiles between them remain unclear. In this study, we investigated the differences in miRNA expression profiles among conventional freezing sperm, droplet vitrification freezing sperm and fresh human sperm. We also analyzed the differences between these methods in terms of differentially expressed miRNAs (DEmiRs) related to early embryonic development and paternal epigenetics. Our results showed no significant differences between the cryopreservation methods in terms of sperm motility ratio, plasma membrane integrity, DNA integrity, mitochondrial membrane potential, acrosome integrity, and ultrastructural damage. However, sperm miRNA-sequencing showed differences between the two methods in terms of the numbers of DEmiRs (28 and 19 with vitrification using a nonpermeable cryoprotectant and the conventional method, respectively) in postthaw and fresh sperm specimens. DEmiRs related to early embryonic development and paternal epigenetics mainly included common DEmiRs between the groups. Our results showed that the differences between conventional freezing and droplet vitrification were minimal in terms of miRNA expression related to embryonic development and epigenetics. Changes in sperm miRNA expression due to freezing are not always detrimental to embryonic development. This study compared differences in miRNA expression profiles before and after cryopreservation between cryopreservation by conventional and vitrification methods. It offers a new perspective to evaluate various methods of sperm cryopreservation.
Asunto(s)
Criopreservación , MicroARNs , Preservación de Semen , Espermatozoides , Vitrificación , Humanos , Masculino , Criopreservación/métodos , MicroARNs/genética , Espermatozoides/metabolismo , Preservación de Semen/métodos , Crioprotectores/farmacología , Motilidad Espermática/genética , CongelaciónRESUMEN
The objective of this study was to investigate the chain mediating effects of depressive symptoms and social participation between functional teeth and cognitive function based on the biopsychosocial model. Data from the 2018 China Health and Retirement Longitudinal Study were analyzed. The findings revealed a favorable connection between the lack of edentulism and cognitive function, persisting even when accounting for the mediating factors of denture usage, depressive symptoms, and social participation. Furthermore, the study identified six indirect pathways in this relationship. The present study has substantiated the correlation between edentulism and cognitive function, thereby proposing that interventions aimed at denture usage, depressive symptoms, and social participation could potentially serve as preventive measures against cognitive decline in elderly individuals afflicted with edentulism. This underscores the significance of addressing these factors to alleviate cognitive decline.
Asunto(s)
Depresión , Participación Social , Humanos , Depresión/psicología , Femenino , China , Participación Social/psicología , Anciano , Masculino , Estudios Longitudinales , Cognición , Disfunción Cognitiva , Dentaduras/psicología , Pueblos del Este de AsiaRESUMEN
This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.
Asunto(s)
Modelos Animales de Enfermedad , Tratamiento con Ondas de Choque Extracorpóreas , Contracción Muscular , Canales Catiónicos TRPV , Vejiga Urinaria , Animales , Femenino , Ratas , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/etiología , Ovariectomía , Ratas Sprague-Dawley , Ovario/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.