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BACKGROUND: Long-term effects of individualized acupuncture in persons with chronic neck pain (CNP) remain unknown. OBJECTIVE: To evaluate the efficacy and safety of pressure pain, sensory-based individualized acupuncture for relieving CNP. DESIGN: A 24-week multicenter randomized controlled clinical trial. (ChiCTR1800016371). SETTING: Outpatient settings at 4 clinical centers in China from May 2018 to March 2020. PARTICIPANTS: 716 participants with CNP. INTERVENTION: Participants were randomly assigned to a waiting list (WL) group or to 1 of 3 interventions, which consisted of 10 sessions over 4 weeks: higher sensitive acupoints (HSA), lower sensitive acupoints (LSA), and sham acupoints (SA) acupuncture groups. MEASUREMENTS: The primary outcome was the change in the visual analogue scale (VAS) score for neck pain (range, 0 to 100) from baseline to 4 weeks, with a difference of 10 points considered the minimum clinically important threshold. The VAS was also assessed every 4 weeks through 24 weeks. RESULTS: The modified intention-to-treat population included 683 participants. The mean baseline VAS was 50.36, 50.10, 49.24, and 49.16 for HSA, LSA, SA, and WL, respectively. Compared with a mean baseline to week 4 change of -12.16 in the HSA group, the mean changes were -10.19 in the LSA group (net difference [ND], -1.97 [95% CI, -5.03 to 1.09]), -6.11 in the SA group (ND, -6.05 [CI, -9.10 to -3.00]), and -2.24 in the WL group (ND, -9.93 [CI, -12.95 to -6.90]). The intervention effects persisted at 24-week follow-up. LIMITATION: Lack of complete blinding and limited generalizability. CONCLUSION: Individualized acupuncture interventions using high- or low-sensitivity acupuncture points were more effective in reducing CNP than SA and WL control groups sustained through 24 weeks, but the magnitude of relative improvement did not reach a minimal clinically important difference. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.
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Drought stress (DS) is one of the abiotic stresses that plants encounter commonly in nature, which affects their life, reduces agricultural output, and prevents crops from growing in certain areas. To enhance plant tolerance against DS, abundant exogenous substances (ESs) have been attempted and proven to be effective in helping plants relieve DS. Understanding the effect of each ES on alleviation of plant DS and mechanisms involved in the DS relieving process has become a research focus and hotspot that has drawn much attention in the field of botany, agronomy, and ecology. With an extensive and comprehensive review and summary of hundred publications, this paper groups various ESs based on their individual effects on alleviating plant/crop DS with details of the underlying mechanisms involved in the DS-relieving process of: (1) synthesizing more osmotic adjustment substances; (2) improving antioxidant pathways; (3) promoting photosynthesis; (4) improving plant nutritional status; and (5) regulating phytohormones. Moreover, a detailed discussion and perspective are given in terms of how to meet the challenges imposed by erratic and severe droughts in the agrosystem through using promising and effective ESs in the right way and at the right time.
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Sequías , Fotosíntesis , Estrés Fisiológico , Reguladores del Crecimiento de las Plantas/metabolismo , Plantas/metabolismo , Antioxidantes/metabolismo , Productos Agrícolas , Fenómenos Fisiológicos de las PlantasRESUMEN
BACKGROUND: Acinetobacter baumannii (A. baumannii) has become a significant nosocomial pathogen globally over the past decade due to the increasing prevalence of antibiotic-resistant isolates. The formation of the mucoid phenotype is a crucial adaptive defense response to external pressure, but the phenotypic and genotypic characteristics and their relationship with sequence types (ST) and K locus (KL) types remain unclear. METHODS: In this study, we screened a total of 736 A. baumannii isolates, from which we identified and characterized 13 mucoid isolates. The study explored the clinical characteristics of patients with mucoid isolates, investigated the mucoid phenotype, performed capsule observation, quantified capsule production, and assessed antimicrobial susceptibility. Subsequently, whole-genome sequencing (WGS) was used to analyze the sequence types (ST), loci for capsular polysaccharide (KL), antibiotic resistance genes, virulence genes, and core-genome single-nucleotide polymorphisms (SNPs). Additionally, the virulence of all mucoid strains was evaluated through serum resistance assay, biofilm-forming assay, and Galleria mellonella survival assay. RESULTS: All mucoid A. baumannii isolates were found to be encapsulated and extremely drug-resistant. Among patients infected with these isolates, 92.3% had pulmonary infections, and the 30-day mortality rate was 61.5%. The analysis revealed that not all strains are highly virulent. Whole-genome sequencing (WGS) identified the sequence types as ST136, ST208, ST381, ST195, and ST281, and the capsular types as KL77, KL7, KL33, KL2, and KL3. The ST208 and KL7 isolates exhibited higher virulence and greater biofilm formation, with KL7 isolates also showing higher capsule production. Despite these differences, no significant variations in virulence genes were observed among the mucoid isolates, except for biofilm-associated and quorum-sensing genes. The highly virulent ST208/KL7 strains (AB276, AB313, and AB552) lacked biofilm-associated genes (csuA/BABCDE), indicating these genes do not directly cause differences in biofilm formation. CONCLUSION: The mucoid A. baumannii isolates were extensively drug-resistant, and infections caused by these isolates could lead to higher mortality. However, not all strains had high virulence, with variations likely related to specific sequence types (ST) and K locus (KL) types.
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Water (H2O) is ubiquitous in the environment and inevitably participates in many surface reactions, including CO oxidation. Acquiring a fundamental understanding of the roles of H2O molecules in CO oxidation poses a challenging but pivotal task in real-life catalysis. Herein, benefiting from state-of-the-art mass-spectrometric experiments and quantum chemical calculations, we identified that the dissociation of a H2O molecule on each of the cerium oxide cluster anions (CeO2)nO- (n = 1-4) at room temperature can create a new atomic oxygen radical (Oâ¢-) that then oxidizes a CO molecule. The size-dependent reactivity of H2O-mediated CO oxidation on (CeO2)nO- clusters was rationalized by the orbital compositions (O2p) and energies of the lowest unoccupied molecular orbitals of active Oâ¢- radicals modified by H2O dissociation. Our findings not only provide new insights into H2O-mediated CO oxidation but also demonstrate the importance of H2O in modulating the reactivity of the Oâ¢- radicals.
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A series of scutellarein 7-l-amino acid carbamate-4'-cycloalkylamine propyl ether conjugates were designed and synthesized for the first time as multifunctional agents for Alzheimer's disease (AD) therapy. The designed compounds exhibited more balanced and effective multi-target potency. Among them, compound 11l, l-Valine carbamate derivative of scutellarein cycloheptylamine ether, exhibited the most potent inhibition of electric eel AChE enzymes and human AChE enzymes, with an IC50 values of 7.04 µM and 9.73 µM, respectively. Moreover, 11l exhibited more potent H3R antagonistic activities than clobenpropit, with an IC50 value of 1.09 nM. Compound 11l not only displayed excellent inhibition of self- and Cu2+-induced Aß1-42 aggregation (95.48 % and 88.63 % inhibition, respectively) but also induced the disassembly of self- and Cu2+-induced Aß fibrils (80.16 % and 89.30 % disaggregation, respectively). Moreover, 11l significantly reduced tau protein hyperphosphorylation induced by Aß25-35. It exhibited effective antioxidant activity and neuroprotective potency, and inhibited RSL3-induced PC12 cell ferroptosis. Assays of hCMEC/D3 and hPepT1-MDCK cell line permeability indicated that 11l would have optimal blood-brain barrier permeability and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11l significantly attenuated learning and memory impairment in an AD mouse model. Finally, a pharmacokinetic characterization of 11l indicated favorable druggability and pharmacokinetic properties. Taken together, our results suggest that 11l is a potential candidate for AD treatment and merits further investigation.
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Acetilcolinesterasa , Enfermedad de Alzheimer , Apigenina , Inhibidores de la Colinesterasa , Antagonistas de los Receptores Histamínicos H3 , Receptores Histamínicos H3 , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/síntesis química , Humanos , Animales , Relación Estructura-Actividad , Acetilcolinesterasa/metabolismo , Ratones , Antagonistas de los Receptores Histamínicos H3/farmacología , Antagonistas de los Receptores Histamínicos H3/química , Antagonistas de los Receptores Histamínicos H3/síntesis química , Ligandos , Apigenina/farmacología , Apigenina/química , Apigenina/síntesis química , Receptores Histamínicos H3/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Electrophorus , Ratas , Fragmentos de Péptidos/metabolismo , Masculino , Células PC12RESUMEN
BACKGROUND: This study aimed to examine the differential variations in the metabolic composition of follicular fluid (FF) among normal-weight patients with polycystic ovary syndrome (PCOS) and controls and to identify potential biomarkers that may offer insights into the early identification and management of these patients. METHODS: We collected FF samples from 45 normal-weight women with PCOS and 36 normal-weight controls without PCOS who were undergoing in vitro fertilization-embryo transfer. An untargeted metabolomic study of collected FF from infertile women was performed using high-performance liquid chromatography-tandem spectrometry (LC-MS). The tendency of the two groups to separate was demonstrated through multivariate analysis. Univariate analysis and variable importance in projection were used to screen out differential metabolites. Metabolic pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a diagnostic model was established using the random forest algorithm. RESULTS: The metabolomics analysis revealed an increase in the expression of 23 metabolites and a decrease in that of 10 metabolites in the FF of normal-weight women with PCOS. According to the KEGG pathway analysis, these differential metabolites primarily participated in the metabolism of glycerophospholipids and the biosynthesis of steroid hormones. Based on the biomarker combination of the top 10 metabolites, the area under the curve value was 0.805. The concentrations of prostaglandin E2 in the FF of individuals with PCOS exhibited an inverse association with the proportion of high-quality embryos (p < 0.05). CONCLUSIONS: Our research identified a distinct metabolic profile of the FF from normal-weight women with PCOS. The results offer a broader comprehension of the pathogenesis and advancement of PCOS, and the detected differential metabolites could be potential biomarkers and targets for the treatment of PCOS.
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INTRODUCTION: Gut microbes and their metabolites play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, which one and how specific gut-derived metabolites affect the progression of DKD remain largely unknown. OBJECTIVES: This study aimed to investigate the potential roles of indole-3-propionic acid (IPA), a microbial metabolite of tryptophan, in DKD. METHODS: Metagenomic sequencing was performed to analyze the microbiome structure in DKD. Metabolomics screening and validation were conducted to identify characteristic metabolites associated with DKD. The protective effect of IPA on DKD glomerular endothelial cells (GECs) was assessed through in vivo and in vitro experiments. Further validation via western blot, immunoprecipitation, gene knockout, and site-directed mutation elucidated the mechanism of IPA on mitochondrial injury. RESULTS: Alterations in gut microbial community structure and dysregulated tryptophan metabolism were evident in DKD mice. Serum IPA levels were significantly reduced in DKD patients and correlated with fasting blood glucose, HbA1c, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). IPA supplementation ameliorated albuminuria, bolstered the integrity of the glomerular filtration barrier, and mitigated mitochondrial impairments in GECs. Mechanistically, IPA hindered SIRT1 phosphorylation-mediated ubiquitin-proteasome degradation, restoring SIRT1's role in promoting PGC-1α deacetylation and nuclear translocation, thereby upregulating genes associated with mitochondrial biosynthesis and antioxidant defense. CONCLUSION: Our findings underscore the potential of the microbial metabolite IPA to attenuate DKD progression, offering novel insights and potential therapeutic strategies for its management.
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Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease, which can lead to cognitive impairment and dementia. Since AD is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between senescence-related genes and proteins (SRGs and SRPs) and the development of AD. Design: The whole study was based on transcriptomic analysis of control and AD brain tissues and Mendelian randomization (MR) analysis. Methods: For transcriptomic analysis, GSE5281 dataset from GEO database contains the transcriptomic data of human brain tissues (n = 161) from control group and AD patients. The expression of SRGs in control and AD brain tissues were compared by Student's t test. For MR analysis, the instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome. The causality between plasma levels of SRPs and AD was explored using GWAS data of AD from Lambert et al. (17,008 cases and 37,154 controls) and further validated by using data from FinnGen consortium (6,489 patients and 170,489 controls). MR estimate was performed using the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. Results: Transcriptomic analysis identified 36 up-regulated (including PLAUR) and 8 down-regulated SRGs in AD brain tissues. In addition, the MR results at both discovery and validation stages supported the causality between plasma levels of PLAUR (IVW-p = 3.04E-2, odds ratio [OR] = 1.15), CD55 (IVW-p = 1.56E-3, OR = 0.86), and SERPINE2 (IVW-p = 2.74E-2, OR = 0.91) and the risk of AD. Conclusion: Our findings identified that PLAUR, as an SRG, may take part in the development of AD and found that high plasma levels of PLAUR was associated with increased risk of AD, indicating that this gene was a risk factor for this disease and providing the rationale of existing drugs or new preventative and therapeutic strategies.
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BACKGROUND: Lennert lymphoma (LL) is a variant of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), also known as a lymphoepithelioid variant of PTCL. Because of the rarity and lack of clear-cut diagnostic criteria, LL is susceptible tomisdiagnosis. Although previously diagnosed with LL might be reclassified and evaluated with the advent of of molecular and/or genetic findings, cytomorphology and immunohistochemistry are still the key to give rise to correct diagnosis. CASE PRESENTATION: We report a case of a patient who was diagnosed as LL based on cytomorphology and immunohistochemistry. Routine stain (Hematoxlin and Eosin-H&E) revealed tumor cells were mainly small to medium-sized CD4(+) T cells, the CD8 +/TIA-1 + cytotoxic cells were less minority, no expressions of follicle helper T cell markers (CD10, BCL6, PD1, CXCL13, ICOS) or CD21(+) hyperplastic FDC network, or proliferation of high edndothelial venules were noted; however, numerous epithelioid histiocytes are noted in the background and scattered EBV(+) cells were also present. The patient was achieved complete remission after six courses of chemotherapy with cyclophosphamide, epirubicin, vincristine, etoposide, and prednisone regimen. She was followed for 5 years without recurrence or progression. CONCLUSIONS: Classic LL is not difficult to diagnose by cytomorphology and immunohistochemistry, and the mutation profiles can be helpful to distinguish LL from other lymphomas.
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Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Inmunohistoquímica , Linfoma de Células T Periférico , Humanos , Biomarcadores de Tumor/análisis , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Gender is a significant risk factor for late-onset Alzheimer's disease (AD), often attributed to the decline of estrogen. The plant estrogen secoisolariciresinol diglucoside (SDG) has demonstrated anti-inflammatory and neuroprotective effects. However, the protective effects and mechanisms of SDG in female AD remain unclear. METHODS: Ten-month-old female APPswe/PSEN1dE9 (APP/PS1) transgenic mice were treated with SDG to assess its potential ameliorative effects on cognitive impairments in a female AD model through a series of behavioral and biochemical experiments. Serum levels of gut microbial metabolites enterodiol (END) and enterolactone (ENL) were quantified using HPLC-MS. Correlation analysis and broad-spectrum antibiotic cocktail (ABx) treatment were employed to demonstrate the involvement of END and ENL in SDG's cognitive improvement effects in female APP/PS1 mice. Additionally, an acute neuroinflammation model was constructed in three-month-old C57BL/6J mice treated with lipopolysaccharide (LPS) and subjected to i.c.v. injection of G15, an inhibitor of G protein-coupled estrogen receptor (GPER), to investigate the mediating role of the estrogen receptor GPER in the cognitive benefits conferred by SDG. RESULTS: SDG administration resulted in significant improvements in spatial, recognition, and working memory in female APP/PS1 mice. Neuroprotective effects were observed, including enhanced expression of CREB/BDNF and PSD-95, reduced ß-amyloid (Aß) deposition, and decreased levels of TNF-α, IL-6, and IL-10. SDG also altered gut microbiota composition, increasing serum levels of END and ENL. Correlation analysis indicated significant associations between END, ENL, cognitive performance, hippocampal Aß-related protein mRNA expression, and cortical neuroinflammatory cytokine levels. The removal of gut microbiota inhibited END and ENL production and eliminated the neuroprotective effects of SDG. Furthermore, GPER was found to mediate the inhibitory effects of SDG on neuroinflammatory responses. CONCLUSION: These findings suggest that SDG promotes the production of gut microbial metabolites END and ENL, which inhibit cerebral ß-amyloid deposition, activate GPER to enhance CREB/BDNF signaling pathways, and suppress neuroinflammatory responses. Consequently, SDG exerts neuroprotective effects and ameliorates cognitive impairments associated with AD in female mice.
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Enfermedad de Alzheimer , Factor Neurotrófico Derivado del Encéfalo , Butileno Glicoles , Disfunción Cognitiva , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Microbioma Gastrointestinal , Glucósidos , Ratones Transgénicos , Enfermedades Neuroinflamatorias , Receptores de Estrógenos , Receptores Acoplados a Proteínas G , Animales , Femenino , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Glucósidos/farmacología , Glucósidos/uso terapéutico , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Butileno Glicoles/farmacología , Butileno Glicoles/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Receptores de Estrógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Tropomyosin (TM) is the main allergen of Macrobrachium nipponense. Recombinant allergens have great prospects in the detection, diagnosis, and treatment of food allergens. The purpose of this study was to compare the differences in structure and allergenicity between natural TM and recombinant TM. Recombinant TM of M. nipponense with a molecular weight of 38 kDa was successfully expressed in the Escherichia coli system. The amino acid sequence as well as secondary structure between natural and recombinant TM were similar, which were verified by mass and CD spectrometry, respectively. Studies showed that both natural TM and recombinant TM had strong allergenicity, and recombinant TM was more allergenic, which could be used as a substitute for natural TM in the diagnosis and treatment of shrimp allergy. This study provided stable and reliable allergen components for the detection of crustacean allergens and the diagnosis and treatment of food allergies caused by crustacean allergens.
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Alérgenos , Hipersensibilidad a los Alimentos , Palaemonidae , Proteínas Recombinantes , Tropomiosina , Animales , Tropomiosina/inmunología , Tropomiosina/química , Tropomiosina/genética , Palaemonidae/inmunología , Palaemonidae/química , Alérgenos/inmunología , Alérgenos/química , Alérgenos/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Hipersensibilidad a los Alimentos/inmunología , Secuencia de Aminoácidos , Humanos , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Proteínas de Artrópodos/genética , Hipersensibilidad a los Mariscos/inmunologíaRESUMEN
BACKGROUND: The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods. METHODS: The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications. RESULTS: Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO. CONCLUSIONS: The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.
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Fertilización In Vitro , Nacimiento Vivo , Redes Neurales de la Computación , Inducción de la Ovulación , Humanos , Fertilización In Vitro/métodos , Femenino , Nacimiento Vivo/epidemiología , Embarazo , Adulto , Estudios Retrospectivos , Inducción de la Ovulación/métodos , Transferencia de Embrión/métodos , Transferencia de Embrión/estadística & datos numéricos , Máquina de Vectores de Soporte , Resultado del Embarazo/epidemiología , Índice de Embarazo , Tasa de NatalidadRESUMEN
OBJECTIVE: To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE. METHODS: A cross-sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non-CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed. RESULTS: The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism-related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%. CONCLUSION: The results of the current study revealed that, compared with the non-CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE.
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PURPOSE: To investigate the factors affecting footplate position and its influence on vault characteristics following implantable collamer lens (ICL) implantation. SETTING: Hunan Provincial People's Hospital, Changsha, China. DESIGN: Retrospective case series. METHODS: This study included 124 patients (124 eyes). Ultrasound biomicroscopy (UBM) was performed to assess the iris and ciliary body morphologies and observe the footplate position. Using multiple linear regression, the relationship between various ocular and ICL parameters and the vault as well as the factors affecting the footplate distance (FD) were analyzed. Based on the FD, three groups were formed: group 1 (<500 µm), group 2 (500-1000 µm), and group 3 (>1000 µm). The distribution of the vault range after surgery was observed for the three groups. RESULTS: Ciliary sulcus angle and FD significantly impacted the vault (adjusted R2=0.190, F=6.763, P<0.001), with FD being the most important factor influencing the vault (Beta=-0.383, P<0.001). Postoperative UBM revealed that the footplate was located at different positions in the posterior chamber, with the majority (52%) being located on the ciliary body. The average size of the four footplate orientations was 0.88±0.24 mm. Multiple linear regression analysis revealed that ciliary body thickness (CBT), iris curvature (IC), and ICL iris contact length (IRCL) significantly influenced the FD (adjusted R2=0.373, F=11.432, P<0.001). The vault range differed significantly among the three groups (X2=32.33, P<0.001). CONCLUSIONS: Different postoperative ICL footplate positions significantly affect the vault. CBT, IC, and IRCL can alter the position of the footplate from the expected position. This study provides reference for ICL size selection and vault prediction.
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The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival.
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Objective: To explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression. Methods: A total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function. Results: The sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P<0.05). The various factors were further analyzed by linear regression, revealing that the insight and treatment attitude of elderly depressed hospitalized patients were mainly related to the Mini-Mental State Examination (MMSE) (ß= 0.225, 95% CI 0.055-0.395, P=0.01), dependent on a caregiver (ß=-5.810, 95% CI -8.086~-3.535, P<0.001), the type of admission (involuntary admission) (ß=-3.365, 95% CI -5.448~-1.283, P=0.002), Functional Activities Questionnaire (FAQ) (ß=-0.156, 95% CI -0.303~-0.010, P=0.037), and length of stay (≤28 days) (ß=2.272, 95% CI 0.055~-4.489, P=0.045). Conclusion: The level of insight was affected by cognitive function, involuntary admission, dependent on a caregiver, social function and length of stay. Future studies should focus on cognitive function recovery, observation of admission mode, and self-care ability in elderly patients with depression.
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The escalating resistance of agricultural pests to chemical insecticides necessitates the development of novel, efficient, and safe biological insecticides. Conus quercinus, a vermivorous cone snail, yields a crude venom rich in peptides for marine worm predation. This study screened six α-conotoxins with insecticidal potential from a previously constructed transcriptome database of C. quercinus, characterized by two disulfide bonds. These conotoxins were derived via solid-phase peptide synthesis (SPPS) and folded using two-step iodine oxidation for further insecticidal activity validation, such as CCK-8 assay and insect bioassay. The final results confirmed the insecticidal activities of the six α-conotoxins, with Qc1.15 and Qc1.18 exhibiting high insecticidal activity. In addition, structural analysis via homology modeling and functional insights from molecular docking offer a preliminary look into their potential insecticidal mechanisms. In summary, this study provides essential references and foundations for developing novel insecticides.
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Conotoxinas , Caracol Conus , Insecticidas , Simulación del Acoplamiento Molecular , Conotoxinas/química , Conotoxinas/farmacología , Conotoxinas/síntesis química , Insecticidas/química , Insecticidas/síntesis química , Insecticidas/farmacología , Animales , Caracol Conus/química , Secuencia de Aminoácidos , Péptidos/química , Péptidos/farmacología , Péptidos/síntesis química , Técnicas de Síntesis en Fase Sólida/métodosRESUMEN
OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Zusanli"(ST36) and"Xuehai"(SP10) on the angiogenesis of the local injured skin tissue in mice with psoriasis, so as to explore its mechanisms underlying improvement of psoriasis-induced skin lesions. METHODS: A total of 24 female BALB/c mice aged 6-8 weeks were randomly divided into control, model and EA groups, with 8 mice in each group. The psoriasis-like skin lesion model was established by application of 5% imiquimod (IMQ) cream to the mice's back skin, 62.5 mg/d, for 7 days after local depilation, and the mice of the control group received local application of an equal amount of petroleum jelly once a day for 7 days. EA stimulation (2 Hz/100 Hz) was applied to ST36 and SP10 for 30 min, once daily for 7 consecutive days. Photos of the topical injured skin at the back were taken every day, and the severity of psoriasis lesions (psoriasis area and severity index ï¼»PASIï¼½) was scaled. Following H.E. staining, the morphological changes in the injured skin tissue were observed with epidermal thickness analyzed, and the Masson staining was used to observe the proportion of collagen fibers in the injured skin tissues. Immunohistochemical method was used to detect the expression of microvascular markers CD31 and vascular endothelial growth factor (VEGF) and the microvascular density (MVD) was calculated. Western blot was used to detect the expression levels of CD31, VEGF proteins and mitogen activated protein kinases (MAPK) signaling pathway related proteins p38, phosphorylated p38 (p-p38), extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK) and p-JNK in the injured skin tissue. RESULTS: Compared with the control group, the mice in the model group showed an evident increase in the erythema score, scales score, skin thickening score and PASI score, epidermal thickness, proportion of the collagen fibers, MVD value of CD31 and VEGF, and expression levels of CD31 and VEGF proteins, and p-p38/p38, p-ERK/ERK and p-JNK/JNK ratios in the injured skin tissue (P<0.001, P<0.01). In contrast to the model group, the EA group had a significant decrease in the levels of all the indexes mentioned above (P<0.05, P<0.01, P<0.001). CONCLUSIONS: EA intervention can improve the psoriasis-like skin lesions induced by IMQ in mice, which may be related with its functions in down-regulating the expression of angiogenic related factors CD31 and VEGF proteins and MAPK signaling pathway related proteins in the topical injured skin tissue.
Asunto(s)
Electroacupuntura , Ratones Endogámicos BALB C , Psoriasis , Factor A de Crecimiento Endotelial Vascular , Animales , Psoriasis/terapia , Psoriasis/metabolismo , Ratones , Femenino , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Piel/irrigación sanguínea , Piel/metabolismo , Neovascularización Patológica/terapia , Neovascularización Patológica/metabolismo , Modelos Animales de Enfermedad , Puntos de Acupuntura , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , AngiogénesisRESUMEN
DNA biosynthesis, a focus of fundamental and applied research, typically involves DNA polymerases by using templates, primers, and dNTPs. Some polymerases can polymerize dNTPs for DNA de novo synthesis, although this is generally to occur randomly. This novel synthesis method has garnered our attention and practical use. Herein, we observed that the addition of endonuclease significantly enhances the efficiency of the de novo synthesis reaction catalyzed by the DNA polymerase. We further investigated the reaction conditions that influence this efficiency. Building on the optimal reaction conditions, we developed a rapid and efficient strategy for preparing DNA hydrogel. Further, coupled with the CRISPR-Cas system, we developed a nucleic acid signal amplification system characterized by versatility, sensitivity, specificity, and no risk of aerosol contamination. We successfully detected viral nucleic acids in clinical samples. In summary, our study demonstrates the significant potential of DNA polymerase- and endonuclease-catalyzed DNA de novo synthesis in diverse applications.