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To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Asunto(s)

Diabetes Mellitus Tipo 2 , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios de Casos y Controles , Insecticidas , Glucemia/análisis , Malatión/análogos & derivados , Compuestos Organotiofosforados , China , Adulto , Inflamación

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Chirality is a ubiquitous phenomenon in nature. The advent of nanomaterials has led to a gradual evolution of chiral studies from the molecular scale to the nanoscale. The emergence of carbon dots (CDs) has inaugurated a novel domain in the scientific and technological realms of carbon nanomaterials. In recent years, CDs have attracted increasing attention due to their luminescent properties, excellent biocompatibility and remarkable bioactivity. However, little attention has been paid to the chirality of the CDs and, in particular, the differences between CDs synthesized from racemic compounds and other chiral CDs, as well as the differences in the biological effects of chiral CDs, remain to be explored. Here, chiral CDs were synthesized from L-/D-/DL-arginine, and the differences in various aspects of chiral CDs were evaluated. We found that L-CDs without extreme differences in structure had brighter fluorescence and a more significant ability of NO generation and lipid droplet inhibition than the other two chiral CDs. Combined with its better drug loading and release ability, we validated its superior efficacy in tumor treatment. Therefore, this study provides a basis for further research on chiral carbon dots and their differences.

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Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate ß-catenin signaling. Furthermore, activation of ß-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

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Mast cell tryptases, a family of serine proteases involved in inflammatory responses and cancer development, present challenges in structural characterization and inhibitor development. We employed state-of-the-art protein structure prediction algorithms to model the three-dimensional structures of tryptases α, ß, δ, γ, and ε with high accuracy. Computational docking identified potential substrates and inhibitors, suggesting overlapping yet distinct activities. Tryptases ß, δ, and ε were predicted to act on phenolic compounds, with ß and ε additionally hydrolyzing cyanides. Tryptase δ may possess unique formyl-CoA dehydrogenase activity. Virtual screening revealed 63 compounds exhibiting strong binding to tryptase ß (TPSB2), 12 exceeding the affinity of the known inhibitor. Notably, the top hit (3-chloro-4-methylbenzimidamide) displayed over 10-fold selectivity for tryptase ß over other isoforms. Our integrative approach combining protein modeling, functional annotation, and molecular docking provides a framework for characterizing tryptase isoforms and developing selective inhibitors of therapeutic potential in inflammatory and cancer conditions.

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BACKGROUND: Advances in minimally invasive surgery and the development of Enhanced Recovery After Surgery (ERAS) have favored the spread of day-surgery programs. Even though Vaginal natural orifice transvaginal endoscopic surgery (vNOTES) is accepted as an innovative treatment for benign ovarian cysts that is rapidly gaining recognition worldwide, the safety and feasibility of same-day surgery (SDS) have yet to be established. OBJECTIVE: This study aimed to evaluate the safety and feasibility of day surgery compared to inpatient surgery of patients undergoing vNOTES for benign ovarian cysts by determining perioperative outcomes. MATERIALS AND METHODS: The study consisted of 213 patients who underwent vNOTES for ovarian cystectomy at a single institution from January 2020 to November 2022. Based on the hospital stay, patients were classified into the same-day surgery group (SDSG) and the inpatient surgery group (ISG); after data processing and screening considering the balance of the two groups, SDSG has 83 samples(n = 83), and ISG has 113 samples(n = 113). The patient's demographic characteristics and follow-up data were collected during the perioperative period by doctors and nurses for medical tracking and analysis purposes and 1-month postoperatively by doctors in charge of their operation. Independent sample t-tests were performed to verify if there was any major difference between these two groups for continuous data like age, BMI, and cyst diameter, and Pearson's chi-squared tests were used to test whether there was a major difference between these two groups for categorical data like cyst count, abdominal surgery history and whether their cyst is bilateral ovarian cysts or not. The association between exhaust time and postoperative characteristics and the association between levels of pain and postoperative characteristics were further analyzed to unveil the confounding factors contributing to the same-day discharge method's quick recovery nature. RESULTS: Upon performing propensity score matching, 196 patients were finally enrolled in this study for the matched comparison, including 83(42.3%) patients in the SDSG and 113(57.7%) patients in the ISG. There was no statistical difference between the two groups in terms of duration of operation (85.0 ± 41.5 min vs. 80.5 ± 33.5 min), estimated blood loss (27.7 ± 28.0 ml vs. 36.3 ± 33.2 ml), preoperative hemoglobin levels (128.8 ± 13.2 g/L vs. 128.6 ± 14.0 g/L), postoperative hemoglobin difference at 24 h (16.5 ± 15.4 g/L vs. 19.3 ± 9.1 g/L), pelvic adhesions (42 (50.6%) vs. 47 (41.6%)), and postoperative complications (7(8.4%) vs. 4(3.5%)). The SDSG group showed less time of feeding/off-bed/exhaust/urination after surgery, shorter hospitalization duration, a lower postoperative 6-hour pain score, and a lower incidence of analgesic drug use. Multiple linear regression analysis showed that advancing the time of postoperative off-bed activity and feeding reduced the postoperative exhaust time by 0.34 (95% CI: 0.185-0.496, 0.34 h, p < 0.001) and 0.299(95% CI: 0.158-0.443, 0.229 h, p = 0.036) hours. In addition, Ordinal logistic regression revealed a correlation between pain scores and bilaterality of cyst, increasing about 25.98 times the risk of pain levels when ovarian cysts are bilateral (OR: 26.98, 95% CI: 1.071-679.859, P = 0.045). CONCLUSION: In this pilot study, same-day discharge after vaginal natural orifice transvaginal endoscopic ovarian cystectomy is safe and feasible. The vNOTES for ovarian cystectomy combined with the same-day discharge shorten the exhaust time and duration of hospitalization, reduce postoperative pain, and lower the use incidence of analgesic drugs.

Asunto(s)

Estudios de Factibilidad , Cirugía Endoscópica por Orificios Naturales , Quistes Ováricos , Vagina , Humanos , Femenino , Quistes Ováricos/cirugía , Adulto , Estudios Retrospectivos , Cirugía Endoscópica por Orificios Naturales/métodos , Vagina/cirugía , Persona de Mediana Edad , Procedimientos Quirúrgicos Ambulatorios/métodos , Tiempo de Internación/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Tempo Operativo

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Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood-tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, 125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.

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Background: Stephania tetrandra has been used for treating rheumatic diseases for thousands of years in rural areas of China. Several studies have found that tetrandrine and fangchinoline can inactivate the PI3K/Akt signaling pathway by reducing the expression and phosphorylation of AKT. However, the mechanism underlying the therapeutic actions of S. tetrandra on RA is not well known. Methods: In this study, we determined the molecular mechanism of the therapeutic effects of the multiple ingredients of S. tetrandra extract (STE) on collagen-induced arthritic (CIA) rats by integrating pharmacometabolomics, proteomics, and PTMomics. Results: In the multi-omics joint analysis, first, the expression signatures of proteins, PTMs, metabolites, and STE ingredients were profiled in CIA rats PBMCs that underwent STE treatment. Bioinformatics analysis were subsequently probed that STE mainly regulated tryptophan metabolism, inflammatory response, and cell adhesion pathways in CIA rats. The interrelated pathways were further constructed, and the findings revealed that STE attenuated the inflammatory response and proliferation of PBMCs in CIA rats by mediating the key targets of the PI3K/Akt pathway, including Hint1, ACP1, FGR, HSP90@157W + dioxidation, and Prkca@220N + 845.4540 Da. The rheumatic functions of Hint1 and ACP1 were further confirmed by applying a transcriptomic data of RA patients who clinically received abatacept therapy. Furthermore, a cross-ome correlation analysis was performed and major in vivo ingredients of STE, including coclaurine-N-glucuronide, Me,coclaurine-O-glc, N-gluA-schefferine, corydamine, corypamine, tetrandrine, and fangchiniline, were found to act on these targerts to inactivate the PI3K/Akt pathway. Conclusion: These results elucidated the molecular mechanism by which the ingredients of STE mediate the expression of the key targets in the PI3K/Akt pathway, leading to anti-rheumatic functions. The findings of this study provided new insights into the synergistic effect of STE against arthritis in rats.

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BACKGROUND: Aflatoxin B1, which can penetrate the blood-brain barrier and kill neural cells, can contaminate traditional herbal medicines, posing a significant risk to human health. The present study examined cellular, cognitive and behavioral consequences of aflatoxin B1 contamination of the anti-osteoporotic medicine Radix Dipsaci. METHODS: A mouse model of osteoporosis was created by treating the animals with all-trans-retinoic acid. Then the animals were treated intragastically with water decoctions of Radix Dipsaci that contained detectable aflatoxin B1 or not. The animals were compared in terms of mineral density and mineral salt content of bone, production of pro-inflammatory factors, neurogenesis and microglial activation in hippocampus, as well as behavior and cognitive function. RESULTS: Contamination of Radix Dipsaci with aflatoxin B1 significantly reduced the medicine's content of bioactive saponins. It destroyed the ability of the herbal decoction to improve mineral density and mineral salt content in the bones of diseased mice, and it induced the production of the oxidative stress marker malondialdehyde as well as the pro-inflammatory cytokines interleukin-1ß and tumor necrosis factor-α. Aflatoxin B1 contamination inhibited formation of new neurons and increased the proportion of activated microglia in the hippocampus. These neurological changes were associated with anhedonia, behavioral despair, and deficits in short-term memory and social memory. CONCLUSION: Contamination of Radix Dipsaci with aflatoxin B1 not only eliminates the herbal decoction's anti-osteoporotic effects, but it also induces neurotoxicity that can lead to cognitive decline and behavioral abnormalities. Such contamination should be avoided through tightly regulated production and quality control of medicinal herbs.

Asunto(s)

Aflatoxina B1 , Cognición , Modelos Animales de Enfermedad , Hipocampo , Neurogénesis , Osteoporosis , Animales , Hipocampo/efectos de los fármacos , Aflatoxina B1/toxicidad , Ratones , Osteoporosis/tratamiento farmacológico , Osteoporosis/inducido químicamente , Cognición/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Dipsacaceae/química , Masculino , Contaminación de Medicamentos , Medicamentos Herbarios Chinos/farmacología

RESUMEN

Plant diseases caused by fungal pathogens pose a great threat to crop production. Conidiation of fungi is critical for disease epidemics and serves as a promising drug target. Here, we show that deacetylation of the FolTFIIS transcription elongation factor is indispensable for Fusarium oxysporum f. sp. lycopersici (Fol) conidiation. Upon microconidiation, Fol decreases K76 acetylation of FolTFIIS by altering the level of controlling enzymes, allowing for its nuclear translocation by FolIws1. Increased nuclear FolTFIIS enhances the transcription of sporulation-related genes and, consequently, enables microconidia production. Deacetylation of FolTFIIS is also critical for the production of macroconidia and chlamydospores, and its homolog has similar functions in Botrytis cinerea. We identify two FolIws1-targeting chemicals that block the conidiation of Fol and have effective activity against a wide range of pathogenic fungi without harm to the hosts. These findings reveal a conserved mechanism of conidiation regulation and provide candidate agrochemicals for disease management.

Asunto(s)

Proteínas Fúngicas , Fusarium , Esporas Fúngicas , Fusarium/metabolismo , Fusarium/efectos de los fármacos , Fusarium/genética , Fusarium/patogenicidad , Esporas Fúngicas/metabolismo , Esporas Fúngicas/efectos de los fármacos , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Acetilación , Enfermedades de las Plantas/microbiología , Núcleo Celular/metabolismo , Regulación Fúngica de la Expresión Génica , Transporte Activo de Núcleo Celular , Botrytis/genética , Botrytis/metabolismo , Botrytis/efectos de los fármacos

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Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

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Materiales Biomiméticos , Fibrosis , Animales , Materiales Biomiméticos/farmacología , Microambiente Celular , Ratones , Humanos

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OBJECTIVE: Health-promoting behaviors carry substantial significance for miners' overall health and well-being. This study aimed to examine the association between cumulative risk (CR) and miners' health-promoting behaviors and test the mediating role of health beliefs in this relationship. METHODS: Data were collected from a sequential survey conducted among 712 frontline miners (Mage=41.7 ± 10.1 years) in China. The survey entailed online questionnaire measurements at three distinct time points, each spaced two weeks apart. This study utilized the conceptual model of health-promoting behaviors, the CR model, and structural equation modeling in the analysis of relationships. RESULTS: CR was negatively related to health-promoting behaviors, with a negative acceleration effect. CR was positively associated with perceived threat in a gradient effect, while negatively associated with perceived benefits in a gradient effect. Furthermore, CR was negatively related to self-efficacy, following a negative acceleration effect. Perceived threat, perceived benefits, and self-efficacy emerged as significant mediators in the relationship between CR and health-promoting behaviors. CONCLUSION: This study highlights the critical role of considering both CR and health beliefs in shaping miners' health-promoting behaviors. Understanding these dynamics is pivotal for developing interventions to enhance miners' health and well-being.

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BACKGROUND CONTEXT: Upper cervical complex fractures are associated with high rates of neurological damage and mortality. The Dickman's classification is widely used in the diagnosis of upper cervical complex fractures. However, it falls short of covering the full spectrum of complex fractures. This limitation hinders effective diagnosis and treatment of these injuries. PURPOSE: To address the diagnostic gap in upper cervical complex fractures, the study introduces a novel classification system for these injuries, assessing its reliability and usability. STUDY DESIGN: Proposal of a new classification system for upper cervical complex fractures. PATIENT SAMPLE: The study comprised the clinical data of 242 patients with upper cervical complex fractures, including 32 patients treated at our hospital, along with an additional 210 cases from the literature. OUTCOME MEASURES: The inter-observer and intra-observer reliability (kappa coefficient, κ) of this classification system were investigated by 3 spine surgeons. The 3 researchers independently re-evaluated the upper cervical complex fracture classification system 3 months later. METHODS: The proposed classification categorizes upper cervical complex fractures into 3 main types: Type I combines odontoid and Hangman's fractures into 2 subtypes; Type II merges C1 with odontoid/Hangman's fractures into 3 subtypes; and Type III encompasses a combination of C1, odontoid, and Hangman's fractures, divided into 2 subtypes. Meanwhile, a questionnaire was administered in 15 assessors to evaluate the system's ease of use and clinical applicability. RESULTS: A total of 45 cases (18.6%) unclassifiable by Dickman's classification were successfully categorized using our system. The mean κ value of inter-observer reliability was 0.783, indicating substantial reliability. The mean κ value of intra-observer reliability was 0.862, indicating almost perfect reliability. Meanwhile, thirteen assessors (87.7%) stated that the classification system is easy to remember, easy to apply, and they expressed intentions to apply it in clinical practice in the future. CONCLUSIONS: This system not only offers high confidence and reproducibility but also serves as a precise guide for clinicians in formulating treatment plans. Future prospective applications are warranted to further evaluate this classification system.

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BACKGROUND: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester. METHODS: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses. RESULTS: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted ß=0.026, 95 % CI: 0.003-0.050). CONCLUSION: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester.

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Depresión , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , China/epidemiología , Adulto , Estudios Prospectivos , Complicaciones del Embarazo/epidemiología , Recién Nacido , Depresión/epidemiología , Trimestres del Embarazo , Nacimiento Prematuro/epidemiología , Resultado del Embarazo/epidemiología , Macrosomía Fetal/epidemiología , Lactante , Recién Nacido Pequeño para la Edad Gestacional

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SMARCA2 and SMARCA4 are the mutually exclusive catalytic subunits of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, and have recently been considered as attractive synthetic lethal targets for PROTAC-based cancer therapy. However, the potential off-tissue toxicity towards normal tissues remains a concern. Here, we optimize a GSH-inducible SMARCA2/4-based PROTAC precursor with selective antitumor activity towards lung cancer cells and negligible cytotoxicity towards normal cells in both in vitro and in vivo studies. The precursor is not bioactive or cytotoxic, but preferentially responds to endogenous GSH in GSH-rich lung cancer cells, releasing active PROTAC to degrade SMARCA2/4 via PROTAC-mediated proteasome pathway. Subsequent xenograft model study reveals that selective SMARCA2/4 degradation in lung tumors triggers DNA damage and apoptosis, which significantly inhibits lung cancer cell proliferation without obvious adverse events towards normal tissues. This study exemplifies the targeted degradation of SMARCA2/4 in lung cancer cells by the GSH-responsive PROTAC precursor, highlighting its potential as an encouraging cancer therapeutic strategy.

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Antineoplásicos , Proliferación Celular , Glutatión , Neoplasias Pulmonares , Factores de Transcripción , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Glutatión/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Apoptosis/efectos de los fármacos , Ratones , Proteínas Nucleares/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Estructura Molecular , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , ADN Helicasas/metabolismo , ADN Helicasas/antagonistas & inhibidores , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismo

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AIM: Minimally invasive spinal trauma surgery includes percutaneous pedicle screw fixation and miniature open anterolateral retractor-based approaches, which can improve surgical outcomes by reducing blood loss, operative time, and postoperative pain. Therefore, this study aimed to evaluate the effect of minimally invasive surgery on pain scores, functional recovery, and postoperative complications in patients with spinal trauma. METHODS: This retrospective study included 100 spinal trauma patients treated in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine between May 2019 and May 2022. Patients who underwent traditional open surgery were included in the traditional group, and those who received percutaneous pedicle screw internal fixation combined with posterior minimally invasive small incision decompression were included in the research group, each comprising 50 patients. The effectiveness of these two surgical approaches was determined by assessing their outcome measures, including surgery-related indices, postoperative pain, spinal morphology, functional recovery, and postoperative complications. RESULTS: Minimally invasive surgery was associated with significantly shorter surgical wounds, length of hospital stay, operative time, and postoperative time-lapse before off-bed activity, and less intraoperative hemorrhage volume and postoperative drainage volume compared to open surgery (p < 0.001). Compared to open surgery, patients with minimally invasive surgery showed significantly lower visual analogue scale (VAS) scores at 3 days, 3 months, and 6 months after surgery and lower Oswestry dysfunction index (ODI) at 7 days and 3 months after surgery (p < 0.05). Furthermore, the difference in the spine morphology between the two arms did not achieve statistical significance (p > 0.05). Additionally, minimally invasive surgery resulted in a significantly lower incidence of postoperative complications than open surgery (p < 0.05). CONCLUSIONS: Minimally invasive surgery causes less surgical damage for patients with spinal trauma, improves surgery-related indexes, alleviates postoperative pain, and provides better morphological and functional recovery of the spine.

Asunto(s)

Procedimientos Quirúrgicos Mínimamente Invasivos , Tornillos Pediculares , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Traumatismos Vertebrales/cirugía , Descompresión Quirúrgica/métodos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Recuperación de la Función , Dimensión del Dolor , Anciano

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Exposure to fine particulate matter (PM2.5) poses numerous health risks, with oxidative potential (OP) serving as a critical marker of its toxicity. Synthetic phenolic antioxidants (SPAs) and bisphenols (BPs) influence reactive oxygen species (ROS) levels in PM2.5, and exposure to these compounds induces oxidative stress in organisms, thereby potentially affecting the OP of PM2.5. We detected 26 phenols (including 12 SPAs, 5 transformation products (TPs), and 9 BPs) in PM2.5 sample collected from October 2018 to September 2021 in Wuhan, China. Among them, 19 substances were detected at a detection frequency greater than 50 % in PM2.5 sample. AO 2246 and BHT were the main components of SPAs, and BHT-Q and BPA had the highest concentrations in TPs and BPs, respectively. PM2.5 mass concentrations and phenolic levels were higher in winter and autumn. Substances within groups were strongly correlated, suggesting the same or similar source of exposure. This finding aid in more precise pollution source identification and is crucial for comprehensively evaluating their combined health effects. Furthermore, we determined the OP of PM2.5 and found that BPs were related to increased OP and ROS. This suggests that the toxicity of PM2.5 is influenced not only by its concentration but also by its chemical composition, with BPs potentially enhancing its toxic effects. These factors should be fully considered when assessing the health impacts of PM2.5.

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Background: Restoring and maintaining sinus rhythm in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has been studied in clinical trials to reduce symptoms and improve quality of life. Limited data exist on the effectiveness of rate or rhythm control therapy in these patients. Methods: Consecutive patients with AF and ACS or referred for PCI were prospectively recruited in Fuwai Hospital during 2017-2020. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, non-central nervous system embolism and ischemia-driven revascularization. Kaplan-Meier curves and Cox regressions were performed to evaluate the association between rhythm/rate control and subsequent outcomes. For the primary endpoints, we used the Benjamini-Hochberg correction for multiple comparisons. Results: A total of 1499 patients with AF and ACS or undergoing PCI were included, with a median follow-up of 34.7 months. Compared to non-rate control, rate control strategy reduced the risk of subsequent MACCEs (adjusted HR, 0.320; 95 % CI 0.220-0.466; p <0.001; *p <0.002) and all-cause death (adjusted HR, 0.148; 95 % CI 0.093-0.236; p <0.001; *p <0.002). Similar trends were observed across all predefined subgroups (p <0.001). In the final multivariate model, rhythm control was not associated with a lower subsequent MACCEs but significantly improved all-cause mortality compared to non-rhythm control (adjusted HR, 0.546; 95 % CI 0.313-0.951; p =0.033; *p =0.044). Conclusions: In this real-world study, rate control strategy was associated with lower risk of MACCEs and all-cause death in AF and ACS or undergoing PCI. Besides, management with rhythm control strategy may improve all-cause mortality.

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Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

RESUMEN

BACKGROUND: This study aims to address challenges in dental pulp regeneration therapy. The heterogeneity of DPSCs poses challenges, especially in stem cell transplantation for clinical use, particularly when sourced from donors of different ages and conditions. METHODS: Pseudotime analysis was employed to analyze single-cell sequencing data, and immunohistochemical studies were conducted to investigate the expression of fibronectin 1 (FN1). We performed in vitro sorting of PDGFRß+ DPSCs using flow cytometry. A series of functional assays, including cell proliferation, scratch, and tube formation assays, were performed to experimentally validate the vasculogenic capabilities of the identified PDGFRß+ DPSC subset. Furthermore, gene-edited mouse models were utilized to demonstrate the importance of PDGFRß+ DPSCs. Transcriptomic sequencing was conducted to compare the differences between PDGFRß+ DPSCs and P1-DPSCs. RESULTS: Single-cell sequencing analysis unveiled a distinct subset, PDGFRß+ DPSCs, characterized by significantly elevated FN1 expression during dental pulp development. Subsequent cell experiments demonstrated that this subset possesses remarkable abilities to promote HUVEC proliferation, migration, and tube formation. Gene-edited mouse models confirmed the vital role of PDGFRß+ DPSCs in dental pulp development. Transcriptomic sequencing and in vitro experiments demonstrated that the PDGFR/PI3K/AKT signaling pathway is a crucial factor mediating the proliferation rate and pro-angiogenic properties of PDGFRß+ DPSCs. CONCLUSION: We defined a new subset, PDGFRß+ DPSCs, characterized by strong proliferative activity and pro-angiogenic capabilities, demonstrating significant clinical translational potential.