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Chemotherapy-based combination regimens are recommended as first-line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD-OxPt (IV) nanoparticles (NPs) via host-guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD-OxPt (IV) NPs exhibit prolonged circulation in the blood and intra-tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD-OxPt (IV) NPs exhibited proton-driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD-OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53-mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino-like cell death and enhanced immunogenicity. Furthermore, DAS@CD-OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.
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BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.
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Antifúngicos , Itraconazol , Microsporum , Tinha do Couro Cabeludo , Humanos , Pré-Escolar , Antifúngicos/uso terapêutico , Masculino , Feminino , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/epidemiologia , Tinha do Couro Cabeludo/microbiologia , Itraconazol/uso terapêutico , China/epidemiologia , Microsporum/isolamento & purificação , Criança , Lactente , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Dermatite Atópica/microbiologia , Fatores de Risco , Adolescente , Adulto , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To observe the clinical efficacy and safety of fire dragon cupping in prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in breast cancer. METHODS: Sixty breast cancer patients receiving medium-high emetogenic chemotherapy regimen were randomly divided into an observation group (30 cases, 3 cases dropped out) and a control group (30 cases, 3 cases dropped out). In both groups, 5 mg tropisetron hydrochloride was given intravenously on the day of chemotherapy and 1st to 3rd days after chemotherapy. In the observation group, fire dragon cupping on the abdomen was applied on 1st, 3rd and 5th days after chemotherapy. The incidence of nausea, vomiting, loss of appetite, abdominal pain, abdominal distension, the severity of nausea, vomiting on 1st to 6th days after chemotherapy, and the duration of nausea, vomiting, loss of appetite were observed in the two groups. The self-rating anxiety scale (SAS) score, general comfort questionnaire scale (GCQ) score before and after treatment and remedy antiemetic medication were observed in the two groups, and the safety was evaluated. RESULTS: On 2nd to 6th days after chemotherapy, the number of patients with nausea, loss of appetite and abdominal distension and nausea scores in the observation group were lower than those in the control group (P<0.05). On 1st to 3rd days after chemotherapy, the number of patients with vomiting and vomiting scores in the observation group were lower than those in the control group (P<0.05). The duration of nausea, vomiting and loss of appetite in the observation group were shorter than those in the control group (P<0.05). In the observation group, there was no significant difference in SAS and GCQ scores before and after treatment (P>0.05). After treatment, the GCQ score in the control group was decreased compared with that before treatment (P<0.05). After treatment, there was no significant difference in SAS and GCQ scores between the two groups (P>0.05). There was no significant difference in the number of patients using remedy medication between the two groups (P>0.05). No adverse reaction occurred during treatment in both groups. CONCLUSION: Fire dragon cupping can effectively reduce the incidence of nausea, vomiting, loss of appetite and the severity of nausea, vomiting related to chemotherapy in breast cancer, and improve patient comfort, and have good safety.
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Neoplasias da Mama , Náusea , Vômito , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Náusea/terapia , Náusea/prevenção & controle , Náusea/etiologia , Náusea/induzido quimicamente , Vômito/terapia , Vômito/induzido quimicamente , Vômito/prevenção & controle , Adulto , Antineoplásicos/efeitos adversos , IdosoRESUMO
Intracerebral hemorrhage (ICH) is a subtype of stroke with the highest fatality and disability rate. Up to now, commonly used first-line therapies have limited value in improving prognosis. Angiogenesis is essential to neurological recovery after ICH. Recent studies have shown that microRNA-451(miR-451) plays an important role in angiogenesis by regulating the function of vascular endothelial cells. We found miR-451 was significantly decreased in the peripheral blood of ICH patients in the acute stage. Based on the clinical findings, we conducted this study to investigate the potential regulatory effect of miR-451 on angiogenesis after ICH. The expression of miR-451 in ICH mouse model and in a hemin toxicity model of human brain microvascular endothelial cells (hBMECs) was decreased the same as in ICH patients. MiR-451 negatively regulated the proliferation, migration, and tube formation of hBMECs in vitro. MiR-451 negatively regulated the microvessel density in the perihematoma tissue and affected neural functional recovery of ICH mouse model. Knockdown of miR-451 could recovered tight junction and protect the integrity of blood-brain barrier after ICH. Based on bioinformatic programs, macrophage migration inhibitory factor (MIF) was predicted to be the target gene and identified to be regulated by miR-451 inhibiting the protein translation. And p-AKT and p-ERK were verified to be downstream of MIF in angiogenesis. These results all suggest that miR-451 will be a potential target for regulating angiogenesis in ICH.
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OBJECTIVES: To evaluate the neutralizing antibody (NAb) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. METHODS: The NAbs against the different viral strains of 490 individuals with SARS-CoV-2 and 187 without SARS-CoV-2 in the Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. RESULTS: In uninfected individuals, limited levels of NAbs were produced against the prototype and variant strains after two doses vaccine but significantly increased after three or four doses of the vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. CONCLUSIONS: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Masculino , Feminino , Adulto , Vacinas contra COVID-19/imunologia , Pessoa de Meia-Idade , Idoso , Adulto Jovem , AdolescenteRESUMO
Nonanal, (E)-2-nonenal, (E,E)-2,4-nonadienal, and (E,Z)-2,6-nonadienal were used to study the effect of number and position of the unsaturated bond in aliphatic aldehydes on meat flavorings. Cysteine-Amadori and thiazolidine derivatives were synthesized, identified by UPLC-TOF/MS and NMR, and quantitatively by UPLC-MS/MS. The polyunsaturated aldehydes exhibited higher inhibition than monounsaturated aldehydes, and monounsaturated aldehydes exhibited higher inhibition than saturated aldehydes, mainly manifested by the inhibition of the cysteine-Amadori formation and acceleration of the thiazolidine derivatives formation. The effect of unsaturated bonds position in aliphatic aldehydes on the initial Maillard reaction stage was similar. The cysteine played an important role in catalyzing the reaction of aliphatic aldehydes. A total of 109 volatile compounds derived by heating prepared thiazolidine derivatives degradation were detected by GC-MS. Formation pathways of volatile compounds were proposed by retro-aldol, oxidation, etc. Particularly, a route to form thiazole by the decarboxylation reaction of thiazolidine derivatives which derivatives from formaldehyde reacting with cysteine was proposed.
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Tumor calcification is found to be associated with the benign prognostic, and which shows considerable promise as a somewhat predictive index of the tumor response clinically. However, calcification is still a missing area in clinical cancer treatment. A specific strategy is proposed for inducing tumor calcification through the synergy of calcium peroxide (CaO2)-based microspheres and transcatheter arterial embolization for the treatment of hepatocellular carcinoma (HCC). The persistent calcium stress in situ specifically leads to powerful tumor calcioptosis, resulting in diffuse calcification and a high-density shadow on computed tomography that enables clear localization of the in vivo tumor site and partial delineation of tumor margins in an orthotopic HCC rabbit model. This osmotic calcification can facilitate tumor clinical diagnosis, which is of great significance in differentiating tumor response during early follow-up periods. Proteome and phosphoproteome analysis identify that calreticulin (CALR) is a crucial target protein involved in tumor calcioptosis. Further fluorescence molecular imaging analysis also indicates that CALR can be used as a prodromal marker of calcification to predict tumor response at an earlier stage in different preclinical rodent models. These findings suggest that upregulated CALR in association with tumor calcification, which may be broadly useful for quick visualization of tumor response.
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Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Animais , Coelhos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Detecção Precoce de Câncer , MicroesferasRESUMO
Refreshing beverages, consumed worldwide, commonly take advantage of caffeine's impacts on attention and motor performance. However, excessive long-term caffeine intake might disturb sleep/wake rhythms and exacerbate daily anxiety. Fish-originated collagen peptides (FCP) are of high nutrient value with stimulating, calming or relaxing effects, which could reduce the excitotoxicity of caffeine. This study aims to investigate two facets: (1) the combined effect of caffeine and FCP (namely C&F) on the cognitive function of sleep-deprived mice by different administration strategies with dose dependence (low and high dose) or time dependence (intervention in a day and prevention for a week); (2) the potential "microbiota-gut-brain" mechanism by which C&F improves sleep deprivation (SD)-induced cognitive impairments. Here, C57BL/6 mice were administered caffeine (10 or 20 mg per kg per bw) combined with FCP (100 or 200 mg per kg per bw) and were then subjected to 48 h SD. The open-field and Morris water maze tests were performed to evaluate the cognitive function and spatial learning capacities of mice. Our results indicated that the cognitive impairments of SD mice were significantly relieved to a different degree by treating C&F in a dose- and time-dependent manner. The pathological observation of the hippocampus indicated both intervention (time of a day) and prevention (time of a week) of the C&F protected brain tissue from SD-induced injuries. The accumulated pro-inflammatory neurometabolites and factors were significantly inhibited by C&F via the hypothalamus-hippocampal circuit. Furthermore, 16S rDNA analysis of colonic contents showed that the level of Lactobacillus murinus was significantly upregulated and that of Clostridia_UCG-014 was suppressed in the C&F group. The receiver operating characteristic (ROC) curve of Lactobacillus murinus indicated a certain diagnostic utility to distinguish C&F intervention (AUC = 0.52) or prevention (AUC = 0.68). Pathways of ko04622 (immune system) and ko00472 (metabolism processes) were significantly regulated by C&F in a time-dependent manner. Based on PICRUSt2 algorithm analysis, C&F might potentially regulate gut microbial functions through several metabolic pathways, including the RIG-I-like receptor signaling pathway and limonene and pinene degradation. In conclusion, C&F plays a key role in brain function and behavior, which could synergistically relieve cognitive impairments via the microbiota-gut-brain axis.
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Cafeína , Disfunção Cognitiva , Lactobacillus , Camundongos , Animais , Cafeína/farmacologia , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Sono , Privação do Sono/tratamento farmacológico , Cognição , Peptídeos/farmacologia , Peptídeos/uso terapêuticoRESUMO
BACKGROUND: The thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China. METHODS: From March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors. RESULTS: Pneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7-3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1-1.8), living with siblings (aOR = 1.3, 95% CI: 1.0-1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1-2.0). In contrast, completion of 3-4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4-0.9). CONCLUSIONS: We established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Humanos , Lactente , Pré-Escolar , Sorogrupo , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Prevalência , Portador Sadio/epidemiologia , China/epidemiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Choerospondiatis is the dried and mature fruit of Choerospondias axillaris (Roxb.) Burtt et Hill. It has been used for a long time in Tibetan and Mongolian medicine, first recorded in the ancient Tibetan medicine book "Medicine Diagnosis of the King of the Moon" in the early 8th century. Fructus Choerospondiatis shows multiple pharmacological activities, especially in treating cardiovascular diseases. AIM OF THIS REVIEW: This paper reviews the progress in research on the botanical characteristics, traditional uses, chemical constituents, pharmacological activity, clinical studies, and quality control of Fructus Choerospondiatis. This review aims to summarize current research and provide a reference for further development and utilization of Fructus Choerospondiatis resources. METHOD: The sources for this review include the Pharmacopeia of the People's Republic of China (2020), theses, and peer-reviewed papers (in both English and Chinese). Theses and papers were downloaded from electronic databases including Web of Science, PubMed, SciFinder, Scholar, Springer, and China National Knowledge Infrastructure.The search terms used were "Choerospondias axillaris", "C. axillaris", "Choerospondias axillaris (Roxb.) Burtt et Hill", "Fructus choerospondiatis", "Guangzao", "Lapsi", and "Lupsi". RESULTS: Fructus Choerospondiatis contains polyphenols, organic acids, amino acids, fatty acids, polysaccharides, and other chemical components. These ingredients contribute to its diverse pharmacological activities such as antioxidant activity, protection against myocardial ischemia-reperfusion injury, anti-myocardial fibrosis, heart rhythm regulation, anti-tumor, liver protection, and immunity enhancement. It also affects the central nervous system, with the ability to repair damaged nerve cells. CONCLUSION: Fructus Choerospondiatis, with its various chemical compositions and pharmacological activities, is a promising medicinal resource. However, it remains under-researched, particularly in pharmacodynamic material basis and quality control. These areas require further exploration by researchers in the future.
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Anacardiaceae , Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Humanos , Frutas , China , Doenças Cardiovasculares/tratamento farmacológico , Controle de Qualidade , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Etnofarmacologia , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
The influence of frying times (0, 2, 4, 6, 8, and 10 min) on the continuous changes in the water distribution and the concentrations of key volatile compounds in chicken breast during the frying process were studied. The fried chicken samples could be distinguished by PCA of E-nose and PLS-DA of GC-MS. A total of 40 volatile compounds were identified by GC-MS, and 28 compounds were verified to be the key compounds after further screening by OAVs. The T22 was increased first and then decreased, while the M22 and M23 in fried chicken were considerably decreased and increased with increasing frying time, respectively. The content of the water and the total peak area of LF-NMR in fried chicken samples during the frying process significantly decreased, and the water was transferred from high to low degrees of freedom. In addition, water content, T21, T22, M22 and L* value were positively correlated with most alcohols and aldehydes, and were negatively correlated with pyrazines, while a*, b*, M23 and all amino acids were positively correlated with pyrazines and were negatively correlated with most alcohols and aldehydes. The results may guide the production processes of fried chicken and help produce high-quality chicken products.
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Aldeídos , Galinhas , Animais , Aldeídos/análise , Álcoois/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , PirazinasRESUMO
PURPOSE: To investigate the baseline levels of serotype-specific IgG antibodies to Streptococcus pneumoniae (S. pneumoniae) and assess their impact on the assessment of vaccine immunogenicity. METHODS: We used a subset of serum samples from a randomized controlled trial. The blood of 584 healthy participants was collected on day 0 before and day 28 after the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination. Serotype-specific IgG against PPSV23-covered serotypes were measured by the World Health Organization (WHO) reference enzyme-linked immunosorbent assay (ELISA). Vaccine immunogenicity was compared using conversion rates (proportion of participants with IgG levels following immunization that are 2-fold greater than the baseline) and geometric mean fold rises (GMFRs) between the two groups, which were grouped according to pre-vaccination (baseline) IgG antibody levels. RESULTS: Our data showed that over half of individuals have baseline IgG levels for 15 out of 23 serotypes above 1.3 µg/mL, and geometric mean concentrations (GMCs) were generally higher in the elderly group and the female group; significant differences were found in 15 serotypes for vaccine immunogenicity based on the seroconversion rate or GMFRs between individuals with baseline IgG ≥ 1.3 µg/mL and individuals with baseline IgG < 1.3 µg/mL. The seroconversion rate decreased with the increase of baseline IgG levels according to a linear regression model. CONCLUSIONS: The assessment of vaccine immunogenicity could be impacted by the fact that many adults had high baseline antibody levels. This study is registered in the Chinese Clinical Trial Registry, number NCT05298800.
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Objective@#To investigate the effect of a comprehensive exercise intervention program combined with diet control on ANGPTL2 and vascular endothelial function in obese male adolescents, and to provide theoretual basis for exercise to reduce the risk of cardiovascular disease in obese male adolescents.@*Methods@#Forty two obese male adolescents and 10 healthy male adolescents were selected, a comprehensive intervention of 6 weeks of exercise combined with diet control was carried out on obese male adolescents, and changes in morphological function, glucose and lipid metabolism, inflammation level and vascular endothelial function were measured before and after the intervention.@*Results@#After 6 weeks of comprehensive intervention, the morphological and functional indicators of obese adolescents were significantly reduced:weight, BMI, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure ( P <0.05); blood lipid levels significantly decreased, including TC, TG and LDL-C ( P <0.05); inflammation levels significantly decreased, including TNF α and ANGPTL2 ( P <0.05); Vascular endothelial function significantly improved:RHI, NO/ET-1, NO, AI( P <0.05). Before and after 6 weeks of comprehensive intervention, the ANGPTL2 of obese adolescents was significantly correlated with weight ( r =0.37), BMI ( r =0.45), RHI ( r =-0.46), NO/ET-1 ( r =-0.41), NO( r =-0.45), and AI ( r =0.33)( P <0.05).@*Conclusion@#The comprehensive intervention can effectively improve the morphological function, blood lipid level and vascular endothelial function of obese male adolescents, and reduce the circulating level of ANGPTL2. ANGPTL2 may be involved in the process of comprehensive intervention to improve the vascular endothelial function of obese adolescents.
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Objective@#To investigate the effects of exercise combined with dietary intervention on glucose and lipid metabolism, liver and kidney function and cardiovascular function in obese adolescents.@*Methods@#Seventy-one obese adolescents were enrolled in this study. Six weeks of exercise combined with dietary intervention were performed to determine anthropometry, glucose and lipid metabolism, liver and kidney function and cardiovascular function before and after intervention.@*Results@#After 6 weeks of comprehensive intervention, in addition to significant improvement in anthropometry indicators, fasting insulin [(18.76±11.46 vs 11.32±6.54)uU/L], LDL-C [(2.96±0.69 vs 2.22±0.62)mmol/L], TG [(1.57±0.82 vs 0.89±0.37)mmol/L] and TC [(4.52±0.76 vs 3.53±0.62)mmol/L] decreased significantly and insulin resistance improved significantly. AST [(36.1±32.28 vs 22.89±7.27)U/L], ALT [(57.42±61.25 vs 27.86±22.12)U/L], blood urea nitrogen [(4.78±0.89 vs 3.44±0.79)mmol/L] and uric acid [(498.83±120.6 vs 471.07±120.96)mmol/L] were significantly decreased and the detection rates of fatty liver and kidney were significantly decreased(P<0.05), RHI(1.34±0.28 vs 1.69±0.45) and nitric oxide/ endothelin-1 (ET-1) (1.69±0.41 vs 2.67±0.86) significantly increased and atherogenic index (3.06±0.96 vs 2.58±0.80) significantly decreased(P<0.01).@*Conclusion@#The comprehensive intervention of exercise combined with diet can effectively improve anthropometry indicators, glycolipid metabolism, liver and kidney function as well as cardiovascular function of obese adolescents.