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Endometrial polyps commonly contribute to female infertility, and hysteroscopic resection is the established surgical approach for their treatment. Numerous resection methods are available, with the most used and cost-effective options being cold resection employing micro-scissors or hot resection using an electric loop. However, both methods involve sharp resection, posing a challenge in achieving complete polyp removal while avoiding damage to the uterine endometrium. To address this issue, this study proposes an innovative approach: the combined use of the 6 Fr micro-scissors and forceps under hysteroscopy. The method entails utilizing 6 Fr micro-scissors to initially remove large polyps, followed by using 6 Fr micro-forceps to extract the remaining polyp tissue expeditiously and bluntly near the basal layer of the endometrium. This approach not only prevents surgical damage to the basal layer of the endometrium but also mitigates the risk of residual polyps resulting from incomplete resection. This method is particularly suitable for women with fertility requirements, offering additional considerations for the selection of treatment options for endometrial polyp resection.
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Histeroscopia , Pólipos , Feminino , Histeroscopia/métodos , Histeroscopia/instrumentação , Pólipos/cirurgia , Humanos , Doenças Uterinas/cirurgia , Instrumentos Cirúrgicos , Endométrio/cirurgia , Endométrio/patologiaRESUMO
Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65-68 % and 90-97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027-1.243). When the daily average relative humidity was 95-97 %, lags of 0-1 d and 8-12 d had greater effects on falls (RR:1.073-1.243). The daily average relative humidities of 62-74 % and 91-97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111-4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.
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This study aims to assess the quality of evidence for the treatment of diabetic retinopathy with traditional Chinese medicine based on the systematic reviews/Meta-analyses of relevant studies. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for the systematic reviews/Meta-analyses of traditional Chinese medicine interventions in diabetic retinopathy published from the inception to November 2023. A Measurement Tool to Assess Systematic Reviews 2(AMSTAR2) scale was used to assess the methodological quality of the included studies. An evidence map was built to present the information on intervention measures, the number of studies included in the systematic reviews/Meta-analyses, research conclusions, and methodological quality assessment results. A total of 51 studies were included. Traditional Chinese medicine interventions accounted for a large proportion of the intervention measures, followed by Chinese patent medicines. The treatment methods mainly included tonifying deficiency, activating blood, and resolving stasis. According to the AMSTAR2 scale assessment results, the descriptions of funding information for included studies, lists of excluded articles, and preliminary research protocols were particularly lacking. The evidence map showed that 48, 2, and 1 studies concluded with beneficial effects, possible beneficial effects, and unclear effects, respectively. On the whole, traditional Chinese medicine demonstrated definite efficacy in the treatment of diabetic retinopathy, while the evidence pre-sents moderate to low quality. It is suggested that higher-quality studies remain to be carried out to provide more evidence.
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Retinopatia Diabética , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/terapia , Humanos , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
BACKGROUND: The natural product paeonol is a rich and sustainable natural bioresource, and its derivatives have various unique biological efficacy. As is well known, Schiff bases are a class of organic compounds with a wide range of biological activities, including anti-fungal, insecticidal, anti-viral, and nematicidal. RESULTS: To discover biorational natural product-based pesticides, nine intermediates (2-10), 12 sulfonylhydrazones (11a-11c, 12a-12c, 13a-13c, and 14a-14c) and 20 benzylidene hydrazones (18a-18r, 19a, and 20a) were synthesized by structural modification of paeonol, and their structures were characterized by proton nuclear magnetic resonance (1H NMR), carbon-13 (13C) NMR, and high-resolution mass spectrometry (HRMS). The stereochemical configurations of compounds 14a, 18d, and 18r were unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete, anti-fungal, and nematicidal agents against three serious agricultural pests, Phytophthora capsici, Fusarium graminearum, and Heterodera glycines were evaluated. Among all tested compounds: (i) compound 7 exhibited promising anti-oomycete against Phytophthora capsici, with a half maximal effective concentration (EC50) value of 15.81 mg L-1; (ii) compounds 2, 7, 10, and 19a displayed promising anti-fungal against F. graminearum, with EC50 values of 12.22, 14.72, 23.39, and 33.10 mg L-1, respectively; (iii) ten compounds (12a-12c, 14c, 18g-18j, 18m, and 19a) showed significant nematicidal activity against H. glycines, with median lethal concentration (LC50) values all less than 30.00 mg L-1. Especially for compound 18g, its LC50 value is the smallest, at 12.65 mg L-1. CONCLUSION: The research results indicate that introducing nitro groups at the C5 position of paeonol, or introducing halogens at both C5 and C3 positions, can significantly enhance its biological activity against Phytophthora capsici, F. graminearum, and H. glycines. © 2024 Society of Chemical Industry.
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In the contemporary realm of athletic training, integrating technology is a pivotal determinant for augmenting athlete performance and refining training outcomes. The amalgamation of multi-target visual modeling with sensor technology imparts an enriched stratum of sports training data. Subsequently, the sensor scale-space transformation accentuates the comprehensive apprehension of data across diverse scales and angles. Hence, within this manuscript, addressing the multi-target tracking intricacies during sports training and competition, we posit a framework that amalgamates the shortest path elucidated by the K shortest paths (KSP) methodology with the pose information emanating from the Alphapose network. This framework recognizes the athlete's shortest path through a convolutional neural network and KSP, followed by the amalgamation of these divergent data sources. The fusion unfolds by incorporating the athlete's pose information grounded in Alphapose, culminating in a comprehensive integration of the two data streams. Consequently, synthesizing alpha-derived athlete information precipitates the ultimate amalgamation of the two information streams. The accomplished fusion, premised on Alphapose, forms the bedrock for multi-target tracking, culminating in a feature-rich synthesis. Empirical results reveal that after integrating these information streams, the Multiple Object Tracking Accuracy (MOTA) index and Global Multiple Object Tracking Accuracy (GMOTA) index surpass those of the solitary information tracking methods, thereby furnishing a technical underpinning and a foundation for information fusion within prospective sports training analysis systems.
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Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1ß3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 µM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and ß-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and ß-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 µM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.
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Rare-earth phosphates were thought to be good candidates as ultraviolet/deep ultraviolet optical materials due to their relatively large bandgap and optical properties. In this paper, the authors screened out a family of XPO4 (X = Sc, Y, La, and Lu) compounds with an enhanced bandgap (HSE06 bandgap ≥ 7.61 eV) and birefringence (0.0934-0.2003@1064 nm) using first-principles calculations. The origin of enhanced optical properties was investigated using projected density of states, distortion indices, and Born effective charges. The results show that the PO4 anionic groups and X-O polyhedra give the main contribution in determining the optical properties, and the PO4 anionic groups give more contribution than other functional basic units. The spin-orbit interaction was also investigated. Similar band structures were found after spin-orbit coupling (SOC) was considered, and slightly enhanced birefringence was found when SOC was applied to these rare-earth phosphates.
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OBJECTIVE: This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework. METHODS: Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota â depression â IBS. RESULTS: Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively. CONCLUSION: These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.
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Depressão , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Análise da Randomização Mendeliana , Síndrome do Intestino Irritável/microbiologia , Humanos , Depressão/microbiologiaRESUMO
Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.
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Digestão , Fezes , Fermentação , Microbioma Gastrointestinal , Polissacarídeos , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Humanos , Fezes/microbiologia , Fezes/química , Digestão/efeitos dos fármacos , Pinellia/química , AnimaisRESUMO
Introducing post-transition metal cations is an excellent strategy for enhancing optical properties. This paper focuses on four isomers, namely the X2PO4I (X = Pb, Sn, Ba, and Sr) series. For the first time, the paper's attention is paid to the changes in electronic structure, as well as refractive indices and birefringence, with and without the inclusion of spin-orbit effects in this series. The first-principles results show that spin-orbit effects of the 5p and 6p states found in these compounds lead to splitting of the bands, narrowing of the band gap, enhancement of the lone-pair stereochemistry, and enhancement of the refractive indices and birefringence. Moreover, a comparison of the lone-pair electron phosphates, X2PO4I (X = Pb and Sn), and the isomeric alkaline earth metal phosphates, X2PO4I (X = Ba and Sr), reveals that changes in the band structure have a greater effect on the enhancement of the birefringence than the slight enhancement of the lone-pair stereochemical activity. This study has important implications for a deeper understanding of the optical properties of crystals and the design of novel optical materials.
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BACKGROUND AND AIMS: A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset. METHODS: Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large-scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions. RESULTS: The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid-positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2. CONCLUSIONS: Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over-reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence.
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Transtornos Relacionados ao Uso de Opioides , Detecção do Abuso de Substâncias , Humanos , Transtornos Relacionados ao Uso de Opioides/urina , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Detecção do Abuso de Substâncias/métodos , Resultado do Tratamento , Tratamento de Substituição de Opiáceos , Análise por Conglomerados , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Ageing is defined as the degeneration of physiological functions in numerous tissues and organs of an organism, which occurs with age. As we age, the gut undergoes a series of changes and weaknesses that may contribute to overall ageing. Emerging evidence suggests that ß-nicotinamide mononucleotide (NMN) plays a role in regulating intestinal function, but there is still a lack of literature on its role in maintaining the colon health of ageing mice. In our research, Zmpste24-/- mice proved that NMN prolonged their life span and delayed senescence. This study was designed to investigate the effects of long-term intervention on regulating colon function in ageing mice. Our results indicated that NMN improved the pathology of intestinal epithelial cells and intestinal permeability by upregulating the expression of intestinal tight junction proteins and the number of goblet cells, increasing the release of anti-inflammatory factors, and increasing beneficial intestinal bacteria. NMN increased the expression of the proteins SIRT1, NMNAT2, and NMNAT3 and decreased the expression of the protein P53. It also regulated the activity of ISCs by increasing Wnt/ß-catenin and Lgr5. Our findings also revealed that NMN caused a significant increase in the relative abundance of Akkermansia muciniphila and Bifidobacterium pseudolongum and notable differences in metabolic pathways related to choline metabolism in cancer. In summary, NMN supplementation can delay frailty in old age, aid healthy ageing, and delay gut ageing.
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Longevidade , Mononucleotídeo de Nicotinamida , Camundongos , Animais , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Envelhecimento , Suplementos Nutricionais , Colo/metabolismoRESUMO
African Swine Fever (ASF), caused by the African swine fever virus (ASFV), has inflicted significant economic losses on the pig industry in China. The key to mitigating its impact lies in accurate screening and strict biosecurity measures. In this regard, the development of colloidal gold immunochromatographic test strips (CGITS) has proven to be an effective method for detecting ASFV antibodies. These test strips are based on the ASFV p30 recombinant protein and corresponding monoclonal antibodies. The design of the test strip incorporates a high-concentration colloidal gold-labeled p30 recombinant protein as the detection sensor, utilizing Staphylococcal Protein A (SPA) as the test line (T line), and p30 monoclonal antibody as the control line (C line). The sensitivity and specificity of the test strip were evaluated after optimizing the labeling concentration, pH, and protein dosage. The research findings revealed that the optimal colloidal gold labeling concentration was 0.05 %, the optimal pH was 8.4, and the optimal protein dosage was 10 µg/mL. Under these conditions, the CGITS demonstrated a detection limit of 1:512 dilution of ASFV standard positive serum, without exhibiting cross-reactivity with antibodies against other viral pathogens. Furthermore, the test strips remained stable for up to 20 days when stored at 50 °C and 4 °C. Comparatively, the CGITS outperformed commercial ELISA kits, displaying a sensitivity of 90.9 % and a specificity of 96.2 %. Subsequently, 108 clinical sera were tested to assess its performance. The data showed that the coincidence rate between the CGITS and ELISA was 93.5 %. In conclusion, the rapid colloidal gold test strip provides an efficient and reliable screening tool for on-site clinical detection of ASF in China. Its accuracy, stability, and simplicity make it a valuable asset in combating the spread of ASF and limiting its impact on the pig industry.
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BACKGROUND: Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the "opposite" voltage-sensing properties of hERG and HCN remains unknown. RESULTS: We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y. CONCLUSIONS: Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.
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Canal de Potássio ERG1 , Ativação do Canal Iônico , Humanos , Sequência de Aminoácidos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Ativação do Canal Iônico/genética , Mutação , Nucleotídeos Cíclicos , Canal de Potássio ERG1/genéticaRESUMO
To better understand the effect of oxygen levels in the storage environment on peanut protein oxidation and explore the mechanism, the functional properties and the oxidation degree of peanut proteins extracted from peanuts under conventional storage (CS), nitrogen modified atmosphere storage (NS, hypoxic) and re-aeration storage (RS) were investigated. Metabolomics and proteomics were employed to analyze peanut's response to hypoxic/re-aeration storage environment. The results showed that NS retarded the decline of the functional properties and the oxidation of peanut proteins, while the process were accelerated after re-aeration. That was the result of the metabolic changes of peanuts under different storage environments. The omics results presented the decreased (NS)/increased (RS) levels of the antioxidant-related proteins acetaldehyde dehydrogenase and glutathione S-transferase, and the inhibition (NS)/activation (RS) of metabolic pathways such as the TCA cycle and the pentose phosphate pathway. This study provided a reference for the re-aeration storage of other agricultural products.
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Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.
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Phosphates, whose obvious disadvantage is the relatively small birefringence, can be overcome by the introduction of post-transition metal cations containing stereochemically active lone-pair electrons. In this paper, two new compounds were successfully explored in the A-Sb-P-O system, i.e. Cs2Sb3O(PO4)3 (CsSbPO) and (NH4)2Sb4O2(H2O)(PO4)2[PO3(OH)]2 (NH4SbPOH). Transmission spectra show that CsSbPO has a surprising transmission range with a UV cutoff edge of 213 nm. First-principles calculations show that both compounds have a wide band gap (5.02 eV for CsSbPO and 5.30 eV for NH4SbPOH) and enlarged birefringence (Δn = 0.034@1064 nm for CsSbPO and Δn = 0.045@1064 nm for NH4SbPOH). The results of real-space atom-cutting investigations show that the distorted [SbOx] polyhedra originating from the asymmetric lone pair electrons give the main contribution to the total birefringence and overcome the disadvantage of small birefringence of phosphates but maintain wide transition windows.
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Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 µM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.
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Neoplasias , Fotoquimioterapia , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Compostos de Boro/química , Neoplasias/tratamento farmacológico , LisossomosRESUMO
Despite significant progress in diagnosis and treatment, asthma remains a serious public health challenge. The conventional therapeutic drugs for asthma often have side effects and unsatisfactory clinical efficacy. Therefore, it is very urgent to develop new drugs to overcome the shortcomings of conventional drugs. Natural polysaccharides provide enormous resources for the development of drugs or health products, and they are receiving a lot of attention from scientists around the world due to their safety, effective anti-inflammatory and immune regulatory properties. Increasing evidence shows that polysaccharides have favorable biological activities in the respiratory disease, including asthma. This review provides an overview of primary literature on the recent advances of polysaccharides from natural resources in the treatment of asthma. The mechanisms and practicability of polysaccharides, including polysaccharides from plants, fungus, bacteria, alga, animals and others are reviewed. Finally, the further research of polysaccharides in the treatment of asthma are discussed. This review can provide a basis for further study of polysaccharides in the treatment of asthma and provides guidance for the development and clinical application of novel asthma treatment drugs.
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Asma , Polissacarídeos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Bactérias , Recursos Naturais , Asma/tratamento farmacológicoRESUMO
Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder. Design, Setting, and Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. Intervention: All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Main Outcomes and Measures: Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. Results: The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). Conclusions and Relevance: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.