RESUMEN
Background: Cardiogenic shock (CS) complicating myocardial infarction is associated with poor outcomes. Data among Asian populations are scarce. We aimed to investigate the long-term outcomes, prognostic factors, and predictors of CS among Asian ST elevation myocardial infarction (STEMI) patients. Methods: This was a retrospective cohort study of consecutive patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI within our regional STEMI network between 2015 and 2019. The long-term outcomes of those with and without CS were compared. Clinical predictors of outcomes and development of CS were investigated. Results: A total of 1791 patients who underwent PPCI were included. Patients completed at least 2 years' follow-up with a median follow-up period of 2.6 years (IQR 1.0, 3,9). Overall, 208/1791 (11.6 %) STEMI patients developed CS. These patients were older (61.1 ± 12.5 vs 57.8 ± 12.2, P < 0.001) and mostly men (87.0 %). All-cause mortality (59.9 % vs 4.7 % P < 0.001), cardiac mortality (43.8 % vs 2.2 %, P < 0.001) and major adverse cardiovascular events (MACE) was significantly higher in the CS group (59.1 % vs 14.0 %, P < 0.001). Independent predictors of survival were higher index LVEF (adjusted hazards ratio [aHR] 0.967, 95 %CI 0.951-0.984, p < 0.001) and higher arterial pH at onset of shock (aHR 0.750, 0.626-0.897, p = 0.002). Increased serum lactate concentration independently predicts poor prognosis (aHR 1.084, 95 % CI 1.046-1.124, p < 0.001). Conclusion: In Asian STEMI patients who underwent PPCI, CS was associated with poor outcomes. Higher LVEF on index admission was associated with better outcomes; while lactic acidosis independently predicted mortality.
RESUMEN
Trajectory similarity computation is very important for trajectory data mining. It is applied into many trajectory mining tasks, including trajectory clustering, trajectory classification and trajectory search etc. So efficient trajectory similarity computation method is very useful for improving trajectory mining result. Nowadays many trajectory similarity computation methods have been proposed. But most of them can not be applied into long trajectories similarity calculation efficiently. So a new algorithm called TrajGAT is proposed. This algorithm can calculate similarity for long trajectories. It treats long trajectory as a long sequence. By doing so, long-term dependency of long trajectory is considered by this algorithm while computing similarity value. But, the spatial feature of long trajectories is not considered. As long trajectory can be presented in many different shapes, if two long trajectories are judged as similar trajectories, the outline shape of these two trajectories should be similar as well. To solve this problem, a new trajectory similarity computation method is proposed in this paper. This method not only takes the long-term dependence feature into consideration, but also considers the outline feature of long trajectory. The proposed method employs GAT-based transformer to extract long-term dependence feature from long trajectory. And it applies Convolutional Neural Network to extract outline feature.
RESUMEN
Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (ß [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (ß [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health.
RESUMEN
BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Células Productoras de Anticuerpos , Inmunoglobulina G , Leucocitos Mononucleares , Receptores de N-Metil-D-Aspartato , Humanos , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/metabolismo , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/metabolismo , Masculino , Femenino , Células Productoras de Anticuerpos/inmunología , Células Productoras de Anticuerpos/metabolismo , Adulto , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Autoanticuerpos/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Persona de Mediana Edad , Adolescente , Adulto Joven , NiñoRESUMEN
Retroperitoneal cysts (RPCs) are rare types of cyst in the retroperitoneal space that are frequently misdiagnosed as gynecological tumors. This case report details, an epidermoid RPC, identified through 2D ultrasound, with attempts to visualize its rendered images using 3D ultrasound. A 39-year-old female patient was admitted to the hospital following the detection of a pelvic mass during a routine physical examination. Initially, the lesion was suspected to be an ovarian tumor, but subsequent ultrasound investigations suggested an epidermoid RPC. This diagnosis was later confirmed by pelvic magnetic resonance imaging. The definitive diagnosis was made following laparoscopic exploration and pathological examination. This case is shared to analyze the ultrasound characteristics of epidermoid RPCs.
Asunto(s)
Quiste Epidérmico , Ultrasonografía , Humanos , Femenino , Adulto , Ultrasonografía/métodos , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Espacio Retroperitoneal/diagnóstico por imagen , Diagnóstico Diferencial , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional/métodosRESUMEN
BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluatedâ¯≤â¯Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab nâ¯=â¯236; placebo nâ¯=â¯237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], pâ¯<â¯0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], pâ¯<â¯0.0001) and TASS (LSD -0.25 [-0.45, -0.05], pâ¯=â¯0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.
RESUMEN
Permeability is a key factor affecting efficient gas drainage from coal seams, and acidification and vibration shock are effective means to increase permeability in original low-permeability coal seams. To study the gas desorption characteristics of coking coal under the coupling effect of mining disturbance and acidification permeability enhancement, taking the coal seam of Shoushan No. 1 coal as the research object, a self-built adsorption-desorption vibration test platform was used. Acid leaching vibration coupling desorption experiments at vibration frequencies of 0, 30, 60, and 100 Hz were conducted on selected particle coals with particle sizes of 0.18-0.25 and 1-3 mm. The experimental results show that the gas desorption amount of particle coal with the same particle size first increases and then decreases with the increase of vibration frequency, among which the desorption effect is the best under 60 Hz vibration condition. Under the condition of fixed vibration frequency, the desorption amount, initial desorption velocity, and velocity attenuation coefficient of particle coal increase as the particle size decreases. Under the same particle size and vibration frequency conditions, the acid leaching and vibration of coal samples have a synergistic effect on gas desorption, which is manifested in the promotion of gas desorption on the outer surface of the coal sample and the surface of open macropores. The research can provide theoretical reference for coal seam acidification and permeability enhancement under the influence of mining disturbance.
RESUMEN
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. METHODS: In this retrospective cross-sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. RESULTS: A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN-BMD, TH-BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11-1.61], p < .05), 1.3 (95% CI [1.05-1.60], p < .05), and 1.26 (95% CI [1.02-1.55], p < .05) for each 1-SD decrease in BMDs of L2-4, FN and TH, respectively. T-scores of < -1 for BMD of L2-4 and FN were independently associated with CVD (p < .05). Subgroup analyses further supported our findings. CONCLUSIONS: The prevalence of CVD was inversely correlated with BMD levels in men with T2DM, particularly at the FN. We hypothesized that monitoring FN-BMD and early intervention would help reduce CVD risk in men with T2DM, especially those with hypertension.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Fracturas Óseas , Masculino , Humanos , Femenino , Densidad Ósea , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/complicaciones , Estudios Transversales , Estudios Retrospectivos , Prevalencia , Absorciometría de Fotón , Fracturas Óseas/etiología , Fracturas Óseas/complicacionesRESUMEN
Melanoma is the most lethal skin malignancy. Fucoxanthin is a marine carotenoid with significant anticancer activities. Intriguingly, Fucoxanthin's impact on human melanoma remains elusive. Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising target in cancer therapy due to its persistent activation in various cancers, including melanoma. Herein, we revealed that Fucoxanthin is cytotoxic to human melanoma cell lines A2758 and A375 while showing limited cytotoxicity to normal human melanocytes. Apoptosis is a primary reason for Fucoxanthin's melanoma cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk drastically abrogated Fucoxanthin-elicited clonogenicity blockage. Besides, Fucoxanthin downregulated tyrosine 705-phosphorylated STAT3 (p-STAT3 (Y705)), either inherently present in melanoma cells or inducible by interleukin 6 (IL-6) stimulation. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, abolished Fucoxanthin-elicited melanoma cell apoptosis and clonogenicity inhibition, supporting the pivotal role of STAT3 blockage in Fucoxanthin's melanoma cytotoxicity. Moreover, Fucoxanthin lowered BCL-xL levels by blocking STAT3 activation, while ectopic BCL-xL expression rescued melanoma cells from Fucoxanthin-induced killing. Lastly, Fucoxanthin was found to diminish the levels of JAK2 with dual phosphorylation at tyrosine residues 1007 and 1008 in melanoma cells, suggesting that Fucoxanthin impairs STAT3 signaling by blocking JAK2 activation. Collectively, we present the first evidence that Fucoxanthin is cytotoxic selectively against human melanoma cells while sparing normal melanocytes. Mechanistically, Fucoxanthin targets the JAK2/STAT3/BCL-xL antiapoptotic axis to provoke melanoma cell death. This discovery implicates the potential application of Fucoxanthin as a chemopreventive or therapeutic strategy for melanoma management.
Asunto(s)
Antineoplásicos , Apoptosis , Melanoma , Transducción de Señal , Xantófilas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Proteína bcl-X/metabolismo , Línea Celular Tumoral , Janus Quinasa 2/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Xantófilas/farmacologíaRESUMEN
NF1 is an autosomal dominant hereditary disease, with a prevalence of at least 1 in 4000-5000 population. The diagnosis criteria of NF1 included typical manifestations such as café-au-lait spots, frecking in the axilla or inguinal region, multiple neurofibromas, Lisch nodeules, and distinctive osseous lesions. Genetic testing shows NF1 mutation. It is essential for tumor surveillance in NF1 patients because their life expectancy is about 54 years due to malignancy. A case of NF-1 patient receive laparoscopic small bowel resection and finally diagnosed as adenocarcinoma and ganglioneuroma. About 25% of NF1 patients had GISTs , most of them were asymptomatic and some may manifest with abdominal pain, bowel obstruction, or gastrointestinal bleeding. CT and MRI are commonly used imaging modalities for GIST in NF1, while they may be negative sometimes. As DBE a more practical and non-invasive method now, we consider it is a valuable method for screening and early detecting small intestine disease for NF1 patients.
RESUMEN
BACKGROUND: This pilot study describes a new technique for creating an arteriovenous fistula (AVF) and presents the preliminary outcomes after 1 year of follow-up. METHODS: The study included 19 patients (10 males, 9 females) with a mean age of 62 years (range 26-88 years). All patients received an AVF using a modified technique in which the surrounding tissues were not removed from the veins and no elastic loops or vascular clamps were used. RESULTS: Immediate patency was obtained for all patients. The proportion of patients experiencing primary patency at 30 days and 6 months was 89.5% and 83.1%, respectively, and cumulative patency at 30 days and 6 months was 100%. At 1 year of follow-up, primary patency was 83.1% and cumulative patency was 100%. CONCLUSIONS: Complete preservation of the surrounding venous tissue in the absence of vascular clamps successfully established AVF, with a high surgical success rate.
RESUMEN
Hepatitis B virus (HBV) infection is a serious global health problem. After the viruses infect the human body, the host can respond to the virus infection by coordinating various cellular responses, in which mitochondria play an important role. Evidence has shown that mitochondrial proteins are involved in host antiviral responses. In this study, we found that the overexpression of TIM22 and TIM29, the members of the inner membrane translocase TIM22 complex, significantly reduced the level of intracellular HBV DNA and RNA and secreted HBV surface antigens and E antigen. The effects of TIM22 and TIM29 on HBV replication and transcription is attributed to the reduction of core promoter activity mediated by the increased expression of SRSF1 which acts as a suppressor of HBV replication. This study provides new evidence for the critical role of mitochondria in the resistance of HBV infection and new targets for the development of treatment against HBV infection.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Factores de Empalme Serina-Arginina , Humanos , Antígenos e de la Hepatitis B/genética , Antígenos e de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Factores de Empalme Serina-Arginina/metabolismo , Replicación Viral , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales/metabolismoRESUMEN
The tumor microenvironment (TME) plays a critical role in tumor progression, with macrophages and tumor cells interacting within the TME, influencing cancer development. Despite the known anticancer properties of calcitriol, its role in the TME remains uncertain. This study aimed to explore the effects of calcitriol on macrophages and cancer cells in the TME and its impact on gastric cancer cell proliferation and cisplatin resistance. In vitro TME models were established using conditioned medium from gastric cancer cells (CCM) and macrophages (MCM) treated with or without calcitriol. The results revealed that calcitriol treatment suppressed the expression of glycolysis-related genes and proteins (GLUT1, HKII, LDHA) in MCM-induced gastric cancer cells, leading to increased cancer cell apoptosis and reduced viability, along with decreased Cyclin D1 gene expression. Moreover, calcitriol treatment inhibited mTOR activation in MCM-induced gastric cancer cells. Additionally, calcitriol hindered CCM-induced M2 macrophage polarization by reducing CD206 expression and increasing TNFα gene expression in THP1-derived macrophages, attenuating cisplatin resistance. These findings suggest that calcitriol may impede gastric cancer progression by targeting glycolysis and M2 macrophage polarization through the regulation of mTOR activation in the TME.
Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Cisplatino/farmacología , Calcitriol/farmacología , Calcitriol/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Macrófagos , Glucólisis , Línea Celular Tumoral , Activación de Macrófagos , Microambiente Tumoral/genéticaRESUMEN
As an important chemical raw material, hydrazine brings convenience to people's lives and provides opportunities for human development. However, the misuse or leakage of hydrazine has brought pollution to the environment, including water, soil and living organisms. At the same time, hydrazine poses a potential threat to human health as a carcinogen. Despite the enormous challenges, it is crucial to develop an effective method to detect hydrazine in environmental samples. In this work, we have synthesized a series of probes based on phenothiazine fluorophore by the introduction of different substituents and developed a novel probe for the detection of hydrazine. The probe is capable of detecting hydrazine in aqueous solutions with high sensitivity and selectivity, and can be easily fabricated into paper test strips for use in in situ samples. In addition, the probe is effective in detecting hydrazine in water, soil, cells, and zebrafish, providing an excellent tool for detecting hydrazine in the environment.
Asunto(s)
Colorantes Fluorescentes , Pez Cebra , Animales , Humanos , Colorantes Fluorescentes/química , Hidrazinas/química , Fenotiazinas , Agua , Suelo , Espectrometría de FluorescenciaRESUMEN
To clarify the causal factors of a case with severe Chlamydia psittaci pneumonia in Jiujiang District, Jiangxi Province and provide a scientific basis for effective prevention and control. Basic information and epidemiological data of the case were collected by epidemiological survey, and the samples from the close contacts and environment were collected for pathogen detection. A 37-year-old female patient was admitted to the hospital due to "fever with cough for five days and worsening dyspnea". The results of targeted next-generation sequencing (tNGS) of pathogenic microorganisms in the bronchoalveolar lavage fluid of the case indicated that the patient was infected with Chlamydia psittaci. Our epidemiological investigation revealed a clear history of chicken and duck exposure. Four throat swab samples of close contacts and one spleen, liver and lung sample of sick chicken and duck were collected for testing. One of the duck tissue samples tested positive, while the other samples were negative. The severe pneumonia was likely caused by exposure to the external environment contaminated by Chlamydia psittaci. Poultry farming should be regulated to prevent the transmission infection from poultry to humans.Additionally, awareness among medical staff should be increased to prevent severe outcomes.
RESUMEN
ObjectiveTo investigate whether elemene(ELE) enhances the anti-glioma efficacy of cabazitaxel(CTX), and prepare a double-targeted cationic liposome(LIP) co-loaded with ELE/CTX for the treatment of glioma, and to achieve the effect of increasing the efficacy and reducing the adverse reactions. Pharmacodynamic tests in vitro were performed to explore the advantages and mechanism of its preparation. MethodELE/CTX@LIP was prepared by high speed shear combined with probe ultrasound, the particle size and potential were characterized by nano-particle size potentiometer, and high performance liquid chromatography(HPLC) was used to determine the encapsulation efficiency and drug loading capacity of CTX/ELE. The cytotoxicity of ELE/CTX in vitro was detected by cell proliferation and activity assay(CCK8). JMP Pro 16 software was used to optimize the process parameters of ELE/CTX@LIP based on encapsulation efficiency. The optimal cationic material type, content and ratio were screened by in vitro cytotoxicity and in vitro cell uptake, on this basis, the dual-targeted cationic liposome T7/arginine glycine aspartate tripeptide sequence(T7/cRGD)-ELE/CTX@CLIP was prepared, the stability of morphology and particle size were characterized, and the effect of T7/cRGD-ELE/CTX@CLIP on the apoptosis inducing ability and cell cycle regulation ability of glioma cells was analyzed by cell cycle and apoptosis. ResultELE/CTX showed stronger anti-glioma activity on C6 and RG2 cells. The results of in vitro cytotoxicity and in vitro cell uptake showed that the amount of cationic material was 0.10% of the total content. The optimum ratio of T7, cRGD and phospholipids was 1∶1∶50. T7/cRGD-ELE/CTX@CLIP[1,2-dilinoleyloxy-3-dimethylaminopropane(Dlin-MC3-DMA)] and T7/cRGD-ELE/CTX@CLIP[1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000(DMG-PEG2000)] showed multi-level spherical nanostructures with particle sizes of 146.0, 111.3 nm, respectively, and were stable in serum. In vitro cytotoxicity results showed that T7/cRGD-ELE/CTX@CLIP had higher cytotoxicity to glioma cells than single-targeted liposomes or dual-targeted non-cationic liposomes. T7/crGD-ELE/CTX@CLIP affected the apoptosis and cycle of glioma cells, the results showed that ELE/CTX combined with liposomes could more effectively activate the apoptosis channel and inhibit the proliferation of glioma cells, and the use of T7/cRGD short peptide and cation modification enhanced the ability of apoptosis induction. ELE/CTX could effectively block glioma cell cycle at G2/M phase, and the effect was enhanced after T7/cRGD targeted modification. ConclusionELE can enhance the anti-glioma effect of CTX. The preparation parameters of ELE/CTX@LIP are stable and feasible. Combined with the in vitro efficacy test, the anti-glioma mechanism of T7/cRGD-ELE/CTX@CLIP is preliminarily revealed.
RESUMEN
Objective:To investigate the characteristics of the nocturnal melatonin secretion concentration and circadian rhythm in patients with wake-up stroke (WUS).Methods:Patients with acute ischemia stroke (AIS) admitted to the Department of Neurology, the Second Affiliated Hospital of Soochow University from October 2019 to August 2022 were enrolled. They were divided into WUS group and non-WUS group. Saliva samples within one week after admission were collected (at 19∶00, 20∶00, 21∶00, 22∶00, and 23∶00) and melatonin concentration was measured. Melatonin secretion curve graph was drawn, dim light melatonin onset (DLMO) was calculated, and circadian rhythms were evaluated. The differences in endogenous circadian rhythms between the WUS group and the non-WUS group were compared. The relevant factors of WUS were determined by multivariate logistic regression analysis. Results:A total of 116 patients with AIS were included, with 79 males (68.1%), aged 59.9±10.3 years; 35 patients (30.2%) were WUS. Univariate analysis showed that there was a statistically significant difference in the infarct site between the WUS group and the non-WUS group ( P=0.019). At 21:00 ( P=0.004) and the average ( P=0.038) nighttime melatonin concentration in the WUS group were significantly lower than those in the non-WUS group, and DLMO showed a significant delay compared to the non-WUS group (21:28:08 vs. 20:57:57; P=0.015). Multivariate logistic regression analysis showed a significant independent correlation between DLMO delay and WUS (odds ratio 1.792, 95% confidence interval 1.123-2.858; P=0.014). Conclusion:Patients with WUS may have endogenous circadian rhythm delay, which is an independent risk factor for WUS.
RESUMEN
Objective To investigate the clinical efficacy of modified Banxia Houpu Decoction plus Deanxit for the treatment of cancer-related depression(CRD)of phlegm blended with qi type.Methods Sixty-four CRD patients with phlegm blended with qi type were randomly divided into the treatment group and the control group,with 32 patients in each group.The control group was given oral use of Deanxit,and the treatment group was treated with modified Banxia Houpu Decoction plus Deanxit orally.The course of treatment covered 4 weeks.The changes of Karnofsky Performance Status(KPS)scores,self-rating depression scale(SDS)scores,and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before and after the treatment.Moreover,the efficacy for improving KPS scores and TCM syndrome efficacy in the two groups were also evaluated.Results(1)After 4 weeks of treatment,the total effective rate for improving KPS scores in the treatment group was 90.63%(29/32),and that in the control group was 78.13%(25/32).The intergroup comparison showed that the efficacy for improving KPS scores in the treatment group was significantly superior to that in the control group(P<0.01).(2)In terms of the efficacy of TCM syndromes,after 4 weeks of treatment,the total effective rate for improving TCM syndrome scores in the treatment group was 87.50%(28/32),and that in the control group was 40.63%(13/32),and the efficacy of TCM syndromes in the treatment group was significantly superior to that in the control group(P<0.05).(3)After treatment,the KPS scores in the treatment group were significantly increased compared with those before treatment(P<0.05),and the KPS scores in the control group tended to increase compared with those before treatment,but the difference was not statistically significant(P>0.05).The intergroup comparison showed that the effect on increasing KPS scores in the treatment group was significantly superior to that in the control group(P<0.05).(4)After treatment,the SDS scores in the two groups were lower than those before treatment(P<0.05),and the effect on lowering SDS scores in the treatment group was significantly superior to that in the control group(P<0.05).(5)After treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P<0.05),and the effect on lowering TCM syndrome scores in the treatment group was significantly superior to that in the control group(P<0.05).Conclusion Modified Banxia Houpu Decoction plus Deanxit exerts certain effect for the treatment of CRD of phlegm blended with qi type.The combined therapy can effectively improve the depression mood and quality of life of the patients,and its efficacy is superior to that of Deanxit alone.
RESUMEN
Objective To investigate the clinical and genetic characteristics of a family with hypokalemic periodic paralysis(HOKPP).Methods The clinical data of one HOKPP family were retrospectively analyzed.Results The proband presented with periodic paralysis,limb weakness and decreased serum potassium(1-2 mmol/L).The proband's father and cousin had similar symptoms.A heterozygous missense variant c.2006G>A(p.R669H)in SCN4A gene was identified in the proband,his father,younger aunt and cousin using gene detection.However,the variant was absent in his elder aunt and younger uncle.Conclusions The family shows irregular dominant inheritance.The severity,frequency and age of onset of male heterozygotes were different,while female heterozygotes had no clinical phenotype.The study first confirms that the R669H variant in SCN4A gene causes complete penetrance in males and carriers in females in Asian populations.