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Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.
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BACKGROUND AND AIMS: Since the onset of the COVID-19 pandemic, a significant rise in mental ill health has been observed globally in young people, particularly those in their final years of secondary school. Students' negative experiences coincide with a critical transitional period which can disrupt milestones in social and educational development. This study aimed to use innovative population-level data to map the impact of the pandemic on students entering higher education. METHODS: Pre-pandemic (2019/2020) and pandemic (2020/2021) tertiary education application data were obtained from the Victorian Tertiary Admissions Centre. Prevalence of applications for special consideration related to mental ill health were compared between cohorts across various geographical areas and applicant demographic subgroups. Relative risk regression models were used to understand the role of different risk factors. RESULTS: Rates of mental health-related special consideration applications increased by 38% among all applications (pre-pandemic: 7.8%, n = 56 916; pandemic: 10.8%, n = 58 260). Highest increases were observed among students in areas with both extended and close-quarter lockdown experiences, and areas impacted by 2019/2020 black summer bushfires. The increases were higher among Year 12 students and students with other special consideration needs (e.g., physical condition, learning disability). Slightly higher increases were observed in areas with higher socio-economic status, which may potentially be related to inequality in mental health service access. CONCLUSION: As consequences of mental health difficulties and academic disruption in youth can be long lasting, it is critical to establish a mental health support framework both in and outside of higher education to facilitate young people's recovery from the pandemic.
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BACKGROUND: Adolescence is a critical period for mental health and social exclusion, a key social determinant of mental health. Early intervention approaches are key to mitigating the impact of mental ill-health during adolescence, however social exclusion can create additional barriers to accessing care. AIM: We aimed to better understand help-seeking experiences of adolescents facing co-occurring social exclusion and mental ill-health, including sources of support, barriers and preferences for service provision. METHOD: Cross-sectional data were analysed, from the 2022 Mission Australia Youth Survey (N = 18,800). Adolescents aged 15 to 19 years were recruited from around Australia, through schools, community organisations and digital platforms. Indices of four domains of social exclusion (housing, finances, relational and education/employment) were created using existing Youth Survey variables, and supplemented with demographic characteristics, psychological distress and help-seeking behaviours (perceived need, mental health supports, barriers to access and preferences). Relationships between social exclusion domains, mental health concerns and help-seeking behaviours were explored using logistic regression models. RESULTS: A total of 9,743 young people reported having needed mental health support, yet only 58.1% reportedly sought support (n = 5,565). Social exclusion domains were associated with different help-seeking behaviours: housing challenges with higher help-seeking (OR = 1.28; 95% CI [1.15, 1.42]); relational difficulties and edu-employment issues with lower (OR = 0.75; 95% CI [0.68, 0.83] and OR = 0.82; 95% CI [0.75, 0.89]). Stigma, confidentiality concerns, cost and not knowing where to seek help were common barriers to help-seeking; those experiencing social exclusion more likely to report these. Participants reported a strong preference for face-to-face support. CONCLUSIONS: This study highlights the additional needs and challenges faced by adolescents dealing with both social exclusion and mental ill-health. With greater barriers to help-seeking, concerted efforts are needed to reduce stigma, improve mental health literacy and increase access to trusted information sources. Further initiatives should focus on structural factors that socially exclude young people and exacerbate inequitable access to mental healthcare.
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Diamondback moth (DBM, Plutella xylostella) is the most significant pest of cruciferous vegetables as they rapidly develop high-level resistance to many insecticides. Monitoring DBM susceptibility and target-site mutation frequency is essential for pest control. In this study, 10 insecticides were tested on 11 field populations. Frequencies of target-site mutations (including para, ace1, Rdl1, RyR1, and nAChRα6 genes) were estimated by pyrosequencing. Insecticides registered after 2007 for DBM control in Taiwan, i.e., spinetoram, chlorantraniliprole, chlorfenapyr, metaflumizone, and flubendiamide, showed >80% mortality toward several populations; Bacillus thurigiensis, emamectin benzoate, and chlorfluazuron showed medium to low efficacy in all populations; and tolfenpyrad and mevinphos were highly ineffective. Susceptibility to insecticides varied substantially among populations: eight out of nine populations were highly susceptible to spinetoram, but only one was susceptible to flubendiamide. Target-site mutations related to organophosphates, pyrethroids, fipronil, and diamides were detected in all populations, but there were few spinosad and spinetoram mutations. Our three-year field study demonstrated rapid efficacy loss for all insecticides tested, particularly for more toxic insecticides. Skipped-generation selection of a field DBM strain to emamectin benzoate, metaflumizone, chlorantraniliprole, and flubendiamide revealed that mortality rates dropped from 60 to 80% to <10% after 6 generations. Next-generation sequencing was performed to identify possible target gene mutations. A resistance management program that considers the instability of resistance to some chemicals and pertinent data on resistance mechanisms should be established. Identifying compounds to overcome high-frequency field DBM point mutations could be beneficial for pest control.
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Resistência a Inseticidas , Inseticidas , Mariposas , Mutação , Animais , Resistência a Inseticidas/genética , Mariposas/efeitos dos fármacos , Mariposas/genética , Inseticidas/farmacologia , Taiwan , Piretrinas/farmacologia , Benzamidas/farmacologia , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Pirazóis , ortoaminobenzoatos , Proteínas de Insetos/genética , Macrolídeos/farmacologia , Fluorocarbonos , Ftalimidas , Semicarbazonas , SulfonasRESUMO
BACKGROUND: Normal keratinocyte differentiation is important for epidermal wound healing. ΔNp63 is a major gene regulating epidermal formation and differentiation. We identified miRNAs targeting ΔNp63 and studied the association between the miRNAs and DNA methylation in keratinocyte differentiation. AIMS: This study aimed to explore the mechanisms regulating ΔNp63 expression during keratinocyte differentiation. METHODS: Bioinformatics analysis was performed to screen the miRNAs targeting ΔNp63 and uncover potential pathway mechanisms. The differentiation model of keratinocytes was established by CaCl2 treatment. Furthermore, the effects of the miRNA transgenic technique on Δ Np63 and keratinocyte differentiation were studied. In addition, the RNA FISH experiment was conducted to detect the location of different miRNAs. A double luciferase reporter experiment was carried out to verify the potential bindings between the miRNAs and ΔNp63. A rescue experiment was also performed to assess the effects of different miRNAs targeting ΔNp63 on keratinocyte differentiation. We analyzed the methylation patterns of the promoter regions of miRNAs using keratinocytes treated with 5-Aza-2'-deoxycytidine. Finally, we designed a methylation rescue experiment to verify the effects of miRNA promoter methylation on keratinocyte differentiation. RESULTS: Bioinformatics analysis showed that the miR-125b-5p and miR-199b-5p binding to the ΔNp63 3'UTR region decreased during skin development. Moreover, such binding may downregulate the PI3K/AKT/mTOR pathway. The expression levels of CK10, Inv, TG1, ΔNp63, and PI3K/AKT/mTOR were all significantly increased during keratinocyte differentiation. Both miR- 125b-5p and miR-199b-5p were localized in the cytoplasm. Luciferase assay results showed that both miR-125b-5p and miR-199b-5p can bind to the 3'UTR region of ΔNp63. Overexpression of ΔNp63 can significantly counteract the inhibitory effect of miRNA mimics on keratinocyte differentiation. Moreover, the promoter regions of both miR-125b-5p and miR-199b-5p had methylation sites, and the methylation levels in those promoter regions were significantly increased during keratinocyte differentiation. 5-Aza-2'-Deoxycytidine treatment increased the expression of miR- 125b-5p and miR-199b-5p and inhibited the differentiation of keratinocytes. Finally, miRNA inhibitors reversed the inhibitory effects of 5-Aza-2'-deoxycytidine on keratinocyte differentiation. CONCLUSION: Promoter hypermethylation in miR-125b-5p and miR-199b-5p seem to promote keratinocyte differentiation via upregulation of ΔNp63 expression and the activation of the PI3K/AKT/mTOR pathway. The findings of this study are helpful for future research on skin development and clinical scar-free healing.
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Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.
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Spontaneous intracerebral hemorrhage (ICH) constitutes a significant portion of acute stroke incidents worldwide, often leading to post-stroke dysphagia (PSD), affecting 50-77% of survivors and worsening patient morbidity. This study aimed to identify predictive variables for PSD among patients with spontaneous ICH. A retrospective cohort study was conducted on adult patients with acute spontaneous ICH, confirmed by brain computed tomography, from June 2019 to June 2023. We analyzed demographic, neuroimaging, and stroke-specific characteristics and rehabilitation indicators. PSD was evaluated using nasogastric (NG) tube retention and the Functional Oral Intake Scale (FOIS) levels at 4 and 12 weeks post-ICH. Statistical analyses involved univariate and multivariate logistic regression to identify PSD predictors. A total of 310 ICH patients were included in the study. At 4 weeks, significant predictors for NG tube retention included 24-hour National Institute of Health Stroke Scale (NIHSS) scores, estimated glomerular filtration rate and sitting balance. At 12 weeks, hospital stay duration and ICH score were significant predictors for NG tube retention. Regarding the FOIS, significant predictors at 4 weeks included higher 24-hour NIHSS scores, compromised sitting balance, immobility-related complications, initial hematoma volume and intraventricular hemorrhages. At 12 weeks, older age and higher 24-hour NIHSS scores significantly predicted lower FOIS levels. Our findings demonstrate that PSD in ICH patients is influenced by a complex interplay of factors, including stroke severity, renal function, and physical impairment. The study highlights the importance of early neurological assessment, physical function, and comprehensive management in improving swallowing outcomes, emphasizing a multifaceted approach to enhancing outcomes for ICH survivors.
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PURPOSE: In the health-care system within hospitals, Taiwanese patients usually play the role of passively cooperating with health-care professionals. Therefore, patients rarely make their own treatment decisions. This study evaluated the level of patient education and patient satisfaction in relation to empowerment level in Taiwan. METHODS: A cross-sectional survey by a self-administered structured questionnaire was carried out with 618 inpatients from the four hospitals. Statistical analyses were then conducted. Analysis of covariance and post-hoc comparison was used to compare differences between the level of patient empowerment, age, and education as covariates in the model. RESULTS: This study found that 21.2% and 35.6% of participants were highly empowered and well empowered, respectively. Years of education is a significant covariate in the counselling domain of patient education. Even after controlling for age and education level, the counselling, answer question and justifying action, providing information scores remain significant for all levels after adjusting for the effects of degree of patient empowerment. Patients with higher empowerment also having more-sufficient patient education, indicating a tendency toward higher patient satisfaction. Patient education and counselling practices in Taiwan's clinical practice could be improved to enhance patient empowerment and ensure health-care systems are person-centred. CONCLUSIONS: To move more toward highly patient empowerment, we suggest that health-care professionals advocate a patient-empowerment approach and to provide more counselling related to patients' illnesses and possible treatments.
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Crop wild relatives (CWR) provide a valuable resource for improving crops. They possess desirable traits that confer resilience to various environmental stresses. To fully utilize crop wild relatives in breeding and conservation programs, it is important to understand the genetic basis of their adaptation. Landscape genomics associates environments with genomic variation and allows for examining the genetic basis of adaptation. Our study examined the differences in allele frequency of 15,416 single nucleotide polymorphisms (SNPs) generated through genotyping by sequencing approach among 153 accessions of 15 wild eggplant relatives and two cultivated species from Africa, the principal hotspot of these wild relatives. We also explored the correlation between these variations and the bioclimatic and soil conditions at their collection sites, providing a comprehensive understanding of the genetic signals of environmental adaptation in African wild eggplant. Redundancy analysis (RDA) results showed that the environmental variation explained 6% while the geographical distances among the collection sites explained 15% of the genomic variation in the eggplant wild relative populations when controlling for population structure. Our findings indicate that even though environmental factors are not the main driver of selection in eggplant wild relatives, it is influential in shaping the genomic variation over time. The selected environmental variables and candidate SNPs effectively revealed grouping patterns according to the environmental characteristics of sampling sites. Using four genotype-environment association methods, we detected 396 candidate SNPs (2.5% of the initial SNPs) associated with eight environmental factors. Some of these SNPs signal genes involved in pathways that help adapt to environmental stresses such as drought, heat, cold, salinity, pests, and diseases. These candidate SNPs will be useful for marker-assisted improvement and characterizing the germplasm of this crop for developing climate-resilient eggplant varieties. The study provides a model for applying landscape genomics to other crops' wild relatives.
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The integration of anionic Ti4L6 (L = embonate) cages and π-conjugated coordination cations into ordered structures can produce high-performance nonlinear optical (NLO) materials. More specifically, by employing Ti4L6 cages for assembly with mixed N,N-chelated and P,P-chelated type conjugated organic ligands and Ag+ ions, three cage-based structures have been synthesized and structurally characterized. Among them, an ion pair structure with strong π-π accumulation exhibits a significant third-order NLO response, and an excellent optical limiting effect has been experimentally verified. This work provides a promising material for NLO applications.
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Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases.
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Adipócitos , Hidrolases de Éster Carboxílico , Inibidores Enzimáticos , Pirazolonas , Humanos , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/citologia , Animais , Camundongos , Pirazolonas/farmacologia , Pirazolonas/química , Pirazolonas/síntese química , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Estrutura Molecular , Células Hep G2 , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células 3T3-L1RESUMO
Different from the previous neutral reaction solvent system, this work explores the synthesis of Al-oxo rings in ionic environments. Deep eutectic solvents (DESs) formed by quaternary ammonium salts hydrogen bond acceptor (HBA) and phenols hydrogen bond donor (HBD) further reduce the melting point of the reaction system and provide an ionic environment. Further, the quaternary ammonium salt was chosen as the HBA because it contains a halogen anion that matches the size of the central cavity of the molecular ring. Based on this thought, five Al8 ion pair cocrystals were synthesized via "DES thermal". The general formula is Q+ â {Cl@[Al8(BD)8(µ2-OH)4L12]} (AlOC-180-AlOC-185, Q+ = tetrabutylammonium, tetrapropylammonium, 1-butyl-3-methylimidazole; HBD = phenol, p-chlorophenol, p-fluorophenol; HL = benzoic acid, 1-naphthoic acid, 1-pyrenecarboxylic acid, anthracene-9-carboxylic acid). Structural studies reveal that the phenol-coordinated Al molecular ring and the quaternary ammonium ion pair form the cocrystal compounds. The halogen anions in the DES component are confined in the center of the molecular ring, and the quaternary ammonium cations are located in the organic shell. Such an adaptive cocrystal binding pattern is particularly evident in the structures coordinated with low-symmetry ligands such as naphthoic acid and pyrene acid. Finally, the optical behavior of these cocrystal compounds is understood from the analysis of crystal structure and theoretical calculation.
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The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was high. These drug-resistant strains showed good replication capacity without serious loss of fitness. In the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. Pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased (1) replication ability in MDCK(P < 0.05) and A549(P < 0.05), (2) neuraminidase enzyme activity, (3) binding ability to both α2,3 and α2,6 receptor, (4) pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), (5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titre). It indicated that through the fine-tuning of HA-NA balance, R229I increased the fitness and changed the antigenicity of H7N9 virus bearing NA 292K. Public health attention to this mechanism needs to be drawn.
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Antivirais , Subtipo H7N9 do Vírus da Influenza A , Neuraminidase , Infecções por Orthomyxoviridae , Oseltamivir , Replicação Viral , Animais , Oseltamivir/farmacologia , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Neuraminidase/genética , Neuraminidase/metabolismo , Cães , Replicação Viral/efeitos dos fármacos , Antivirais/farmacologia , Humanos , Camundongos , Infecções por Orthomyxoviridae/virologia , Células Madin Darby de Rim Canino , Células A549 , Camundongos Endogâmicos C57BL , Farmacorresistência Viral/genética , Substituição de Aminoácidos , Influenza Humana/virologia , Furões , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Feminino , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
One new flavonostilbene glycoside, polygonflavanol C (1), two new dimeric stilbene glycosides, multiflorumiside M and multiflorumiside N (2-3), one new diphenyl ethanol glycoside, (R)-2,3,5,4'-tetrahydroxy-diphenylethanol 2-O-ß-D-glucopyranoside (4), and one new deoxybenzoin glycoside, 2,4,3',5'-tetrahydroxy-6-methyl-deoxybenzoin 2-O-ß-D-glucopyranoside (5), together with six known ones (6-11), were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by the comprehensive spectroscopic analyses. In addition, compounds 1 and 7 showed significantly in vitro anti-inflammatory activity.
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PURPOSE: Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS: We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. RESULTS: A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION: Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.
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Derivações do Líquido Cefalorraquidiano , Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Ventriculostomia , Humanos , Hidrocefalia/cirurgia , Ventriculostomia/métodos , Masculino , Feminino , Taiwan/epidemiologia , Pré-Escolar , Criança , Lactente , Estudos Retrospectivos , Terceiro Ventrículo/cirurgia , Adolescente , Derivações do Líquido Cefalorraquidiano/métodos , Neuroendoscopia/métodos , Reoperação/estatística & dados numéricos , Estudos de Coortes , Recém-Nascido , Resultado do Tratamento , Adulto JovemRESUMO
Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.
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In this work, we developed a ratiometric fluorescent probe (NT) based on ICT framework in near-infrared (NIR) which could detect pH and viscosity simultaneously. Long emission wavelength in NIR could protect the probe from interference of background fluorescence and improve the accuracy of the test. Due to the presence of thiazole-salt, the probe possessed good water solubility and could respond immediately to pH in water system. The pH values measured by NT in the actual samples were not much different from that measured by the pH meter, therefore, NT could give excellent accuracy. NT realized the reversible detection of pH by protonation and deprotonation. NT was used successfully to detect the pH of actual water samples, human serum and meat, as well as the viscosity variation caused by thickeners. Additionally, NT could monitor the changes of pH and viscosity in living cells. Therefore, the novel probe exhibited potential application in the fields of the environment, human health and food safety evaluation.
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Corantes Fluorescentes , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Viscosidade , Humanos , Espectrometria de Fluorescência , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Carne/análise , Células HeLa , Água/químicaRESUMO
BACKGROUND: Aedes aegypti is a widespread mosquito in tropical and subtropical regions that causes significant mortality and morbidity in humans by transmitting diseases, such as dengue fever and Zika virus disease. Synthetic insecticides, such as pyrethroids, have been used to control Ae. aegypti, but these insecticides can also affect nontarget organisms and contaminate soil and water. This study aimed to investigate the mosquitocidal activity of Pseudomonas mosselii isolated from pond sludge against larvae of Ae. aegypti. RESULTS: Based on the initial results, similar time-course profiles were obtained for the mosquitocidal activity of the bacterial culture and its supernatant, and the pellet resuspended in Luria-Bertani (LB) medium also showed delayed toxicity. These results imply that the toxic component can be released into the medium from live bacteria. Further research indicated that the toxic component appeared in the supernatant approximately 4 h after a 3-mL stock was cultured in 200 mL of LB medium. The stabilities of the P. mosselii culture and supernatant stored at different temperatures were also evaluated, and the best culture stability was obtained at 28 °C and supernatant stability at 4 °C. The bacterial culture and supernatant were toxic to larvae and pupae of not only susceptible Ae. aegypti but also pyrethroid-resistant strains. CONCLUSION: This study highlights the value of the mosquitocidal activity of P. mosselii, which has potential as an alternative insecticide to control pyrethroid-resistant Ae. aegypti in the field. © 2024 Society of Chemical Industry.
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Aedes , Resistência a Inseticidas , Inseticidas , Larva , Pseudomonas , Piretrinas , Aedes/efeitos dos fármacos , Animais , Piretrinas/farmacologia , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Inseticidas/farmacologia , Pseudomonas/efeitos dos fármacos , Controle de Mosquitos/métodos , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Controle Biológico de Vetores/métodosRESUMO
Our previous research identified interleukin-4 (IL-4) as a key regulator of glucose/lipid metabolism, circulatory leptin levels, and insulin action, suggesting its potential as a therapeutic target for obesity and related complications. This study aimed to further elucidate the role of IL-4 in regulating hypothalamic appetite-controlling neuropeptides using leptin dysfunctional Leptin145E/145E mice as the experimental model. IL-4 significantly reduces body weight, food intake, and serum glucose levels. Our data demonstrated that IL-4 exhibits multiple functions in regulating hypothalamic appetite control, including downregulating orexigenic agouti-related peptide and neuropeptide Y levels, promoting expression of anorexigenic proopiomelanocortin, alleviating microenvironmental hypothalamic inflammation, enhancing leptin and insulin pathway, and attenuating insulin resistance. Furthermore, IL-4 promotes uncoupling protein 1 expression of white adipose tissue (WAT), suggesting its role in triggering WAT-beige switch. In summary, this study uncovers novel function of IL-4 in mediating food-intake behaviors and metabolic efficiency by regulating hypothalamic appetite-control and WAT browning activities. These findings support the therapeutic potential of targeting hypothalamic inflammation and reducing adiposity through IL-4 intervention for tackling the pandemic increasing prevalence of obesity and associated metabolic disorders.
Assuntos
Hipotálamo , Insulina , Interleucina-4 , Leptina , Transdução de Sinais , Animais , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Interleucina-4/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Leptina/metabolismo , Insulina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Janus Quinases/metabolismo , Regulação do Apetite/efeitos dos fármacos , Apetite/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismoRESUMO
PURPOSE: Stroke survivors and their informal family caregivers may share the impact of the disease, which may affect family functioning and quality of life (QoL) for both. This study compared the perceptions of stroke survivors and informal family caregivers regarding family functioning and QoL and examined the QoL of those reporting effective versus ineffective family functioning. METHODS: A cross-sectional study design and convenience sampling were used. Stroke survivor-informal family caregiver dyads were recruited from a medical university hospital. We assessed participants' demographic and clinical variables, including disease severity, family functioning, and QoL. Independent t-test, paired t-test, Wilcoxon signed-rank test, and Mann-Whitney U test were used to analyze the data. RESULTS: Seventy-one stroke survivor-informal family caregiver dyads participated in the current study. Most stroke survivors and informal family caregivers reported effective family functioning, with no significant differences. However, significant differences existed in the seven domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, and role-emotional) of QoL, except emotional health. Stroke survivors reporting ineffective family functioning had a significantly lower mental component summary score, unlike informal family caregivers. CONCLUSIONS: Our findings suggest that family functioning is crucial to ensure stroke survivors' QoL, particularly regarding their mental health. Health professionals should prioritize mental health assessments and provide appropriate care interventions for stroke survivors in the first 1-6 months after stroke onset.