Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Periodontitis and osteoporosis: a two-sample Mendelian randomization analysis

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

Physical Fitness Parameters of Elite Chinese Wheelchair Curlers / Parámetros de Aptitud Física de Curlers en Silla de Ruedas Chinos de Élite

SUMMARY: Few international studies have analyzed the characteristics of elite wheelchair curlers competing on the international stage. This study aims to investigate the physical fitness parameters of elite Chinese wheelchair curlers and explore the corresponding training enlightenment. Sixteen wheelchair curlers from the Chinese national team, including six male and two female Winter Paralympic gold medalists, were selected as research participants. The following parameters were measured: age, training age, height, weight, body fat percentage, grip strength, absolute bench press strength, and 5-km wheelchair push-timing test. Compared with ordinary curlers of the Chinese wheelchair curling team, elite curlers were older in age and training age; male curlers were shorter, whereas female curlers were taller. However, their weight and body fat percentage were lower, and their grip strength, absolute strength in the bench press, and 5-k wheelchair push-timing test were better. From an athlete development and physical training perspective, wheelchair curlers should increase training years in order to accumulate competition experience. Additionally, these athletes should manage their body weight and fat percentage, and improve their upper limb strength and aerobic capacity.

Pocos estudios internacionales han analizado las características de los curlers en silla de ruedas de élite que compiten en el escenario internacional. Este estudio tiene como objetivo investigar los parámetros de aptitud física de los bigudíes chinos en silla de ruedas de élite y explorar la iluminación del entrenamiento correspondiente. Se seleccionaron como participantes de la investigación dieciséis curlers en silla de ruedas del equipo nacional chino, incluidos seis medallistas de oro masculinos y dos femeninos de los Juegos Paralímpicos de Invierno. Se midieron los siguientes parámetros: edad, edad de entrenamiento, altura, peso, porcentaje de grasa corporal, fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5 km. En comparación con los curlers ordinarios del equipo chino de curling en silla de ruedas, los curlers de élite eran mayores en edad y tiempo de entrenamiento; Los curlers masculinos eran más bajos, mientras que las mujeres eran más altas. Sin embargo, su peso y porcentaje de grasa corporal fueron menores, y su fuerza de agarre, fuerza absoluta en press de banca y prueba de sincronización de empuje en silla de ruedas de 5-k fueron mejores. Desde la perspectiva del desarrollo del atleta y del entrenamiento físico, los curlers en silla de ruedas deberían aumentar los años de entrenamiento para acumular experiencia en competencia. Además, estos deportistas deben controlar su peso corporal y porcentaje de grasa, y mejorar la fuerza de sus miembros superiores y su capacidad aeróbica.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Acute sarcoidosis Löfgren Syndrome treated by Chinese medicinal formula based on Syndrome Differentiation: a case - based review / Tratamiento de síndrome de Löfgren de sarcoidosis con fórmula medicinal china basada en diferenciación de síndrome: una revisión basada en casos

Löfgren syndrome (LS) is a unique acute manifestation of sarcoidosis and characterized by erythema nodosum, bilateral hilar lymphadenectasis, and/or bilateral ankle arthritis or periarthritis. A 37 - year - old female patient with LS presented with fever accompanied by multiple joint swelling and pain, nodular skin erythema, and bilateral hilar lymphadenectasis. The patient had received treatment involving non - steroidal anti - inflammatory drugs and glucocorticoids in other hospitals, but the effects were poor, and the conditions reemerged. The LS duration has lasted for more than 3 months. Following traditional Chinese medicine (TCM) treatment, syndrome differentiation as well as giving patients oral Chinese medicine decoction, the symptoms of the patient were rapidly relieved within one week and did not recur during a six - month follow - up period. This case is the first clinical report of acute sarcoidosis LS treated using T CM and reflects the significant advantages of this form of therapy in emergency treatment

El síndrome de Löfgren (LS) es una manifest ación única y aguda de sarcoidosis, caracterizada por eritrema nodoso, linfadenectasis hilar bilateral, y/o a r tritis de tobillo bilateral o periartritis. Una paciente de 37 años de sexo femenino con LS se presentó con fiebre, acompañada de inflamación y do lor múltiple de articulaciones, eritrema nodular cutáneo, y linfadenectasis hilar bilateral. La paciente recibió un tratamiento que consistió en antiinflamatorios no esteroidales y glucocorticoides en otros hospitales, pero los efectos fueron leves y las c ondiciones reemergieron. El LS ha durado más de tres meses. Siguiendo el tratamiento de medicina tradicional china (MTC), la diferenciación de síndrome, así como darles a los pacientes una decocción de medicina china por vía oral, los síntomas de la pacien te rápidamente fueron aliviados en el curso de una semana y no recidivaron durante los seis meses de un seguimiento. El caso es el primer reporte clínico de tratamiento de sarcoidosis aguda asociada a LS usando TCM y refleja las significativas ventajas de esta forma de terapia en el tratamiento de emergencia.

Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1

BACKGROUND: Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. RESULTS: In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. CONCLUSIONS: Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Diagnostic value of a computer-assisted diagnosis system for the ultrasound features in thyroid nodules

ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in "aspect ratio" were 95.6%, 96.2%, and 95.4%, in "margin irregularity" were 90.7%, 90.5%, and 90.9%, in "margin smoothness" were 85.8%, 88.5%, and 83.0%, in "calcification" were 83.6%, 81.7%, and 82.0%, in "homogeneity" were 88.9%, 90.6%, and 82.2%, in "major echo" were 85.3%, 88.0%, and 85.4%, and in "contains very hypoechoic echo" were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

Corneal reshaping: an experiment with a type I collagen-based vitrigel for remodeling porcine corneas / Remodelamento corneano: relato de um experimento com um vitrigel a base de colágeno tipo I para remodelamento de córneas porcinas

ABSTRACT Purpose: This study aimed to report an experiment designed to determine anatomical changes in porcine corneas following placement of a novel polymer implant into the cornea. Methods: An ex vivo porcine eye model was used. A novel type I collagen-based vitrigel implant (6 mm in diameter) was shaped with an excimer laser on the posterior surface to create three planoconcave shapes. Implants were inserted into a manually dissected stromal pocket at a depth of approximately 200 μm. Three treatment groups were defined: group A (n=3), maximal ablation depth 70 μm; Group B (n=3), maximal ablation depth 64 μm; and group C (n=3), maximal ablation depth 104 μm, with a central hole. A control group (D, n=3) was included, in which a stromal pocket was created but biomaterial was not inserted. Eyes were evaluated by optical coherence tomography (OCT) and corneal tomography. Results: Corneal tomography showed a trend for a decreased mean keratometry in all four groups. Optical coherence tomography showed corneas with implants placed within the anterior stroma and visible flattening, whereas the corneas in the control group did not qualitatively change shape. Conclusions: The novel planoconcave biomaterial implant described herein could reshape the cornea in an ex vivo model, resulting in the flattening of the cornea. Further studies are needed using in vivo animal models to confirm such findings.

RESUMO Objetivo: Relatar um experimento projetado para determinar alterações anatômicas em córneas porcinas após a colocação de um novo implante de polímero na córnea. Métodos: Foi utilizado olho de porco ex vivo. Um novo agente modelador biocompatível, de colágeno tipo 1, com 6mm de diâmetro foi moldado com excimer laser em sua face posterior, para criar três formatos planocôncavos. Os implantes foram inseridos dentro de um bolsão, dissecado manualmente, a 200 micrômetros (μm). Foram definidos três grupos de tratamento: grupo A (n=3), teve a profundidade máxima de ablação de 70 μm; o grupo B (n=3), profundidade máxima de ablação de 64 μm; e o grupo C (n=3), profundidade máxima de ablação de 104 μm, com buraco central. O grupo controle, D (n=3), foi incluído, com a criação do bolsão estromal, porém sem inserir o material. A avaliação desses olhos foi realizada por tomografia de coerência óptica (OCT) e por tomografia corneana. Resultados: A tomografia corneana mostrou uma tendência para diminuição da ceratometria média em todos os 4 grupos. A tomografia de coerência óptica mostrou córneas com implantes localizados no estroma anterior e aplanamento visível, enquanto as córneas não mudaram qualitativamente o formato no grupo controle. Conclusões: O novo implante de biomaterial planocôncavo descrito aqui foi capaz de remodelar a córnea em modelo de animal ex vivo, resultando no aplanamento corneano. Novos estudos são necessários usando modelos animais in vivo para confirmar tais achados.

Application of Cut-and-Sew Technique in Thoracoscopic Minimally Invasive Mitral Valve Surgery and Concomitant Maze Procedure

ABSTRACT Introduction: Atrial fibrillation is one of the common complications of mitral valve disease. Currently, in the absence of freezing equipment, it's still impossible to fully conduct a minimally invasive Cox-maze IV procedure to treat atrial fibrillation. Methods: We analyzed the clinical data of 28 patients who underwent thoracoscopic minimally invasive mitral valve full maze surgery in our hospital from October 2021 to September 2022; 13 patients were male and 15 were female, three suffered from paroxysmal atrial fibrillation, and 25 suffered from permanent atrial fibrillation; average age was 61.88±8.30 years, and mean preoperative left atrial diameter was 47.12±8.34 mm. Isolation of left atrial posterior wall (box lesion) was completed in all patients by cut-and-sew technique and bipolar clamp ablation. Results: For these subjects, the median cardiopulmonary bypass time was 169 (109.75-202.75) minutes, aortic cross-clamping time was 106 (77.75-125.50) minutes, and ventilator assistance time was 6.5 (0-10) hours. Among them, eight subjects had the endotracheal tubes removed immediately after surgical operation. Three subjects were in the blanking period; two subjects still had atrial fibrillation at three months after operation, one of whom resumed sinus rhythm after electrical cardioversion therapy; and all the remaining 23 subjects had sinus rhythm. Conclusion: The minimally invasive cut-and-sew technique for electrical isolation of left pulmonary veins can improve sinus conversion rate of patients suffering from both mitral valve disease and atrial fibrillation. In selected subjects, it is safe and has good results in the short-term postoperative period.

Changes related to muscle autophagy after exhaustive exercise and blunt trauma / Cambios relacionados con la autofagia muscular tras ejercicio exhaustivo y traumatismo contuso / Alterações relacionadas à autofagia muscular após exercício exaustivo e trauma contuso

ABSTRACT Objective: To study the temporal changes of autophagy related factors in skeletal muscle of rats after exhaustive exercise and blunt trauma. Methods: Forty-two male SD rats were divided into 7 groups with 6 rats in each group: Quiet control group (C), immediately after exhaustive exercise (E0), 24 hours after exhaustive exercise (E24), 48 hours after exhaustive exercise (E48), immediately after blunt trauma (D0), 24 hours after blunt trauma (D24), 48 hours after blunt trauma (D48). All groups of rats were killed and samped respectively at different time points specified above, and the right gastrocnemius muscle was taken, which was divided into two parts, one for mRNAs of, Lamp-2, BNIP3 and NIX by real-time fluorescent quantitative PCR, and the other for p62 protein by Western blotting. Results: (1) Compared with group C, mRNA levels of p62, Lamp-2 and NIX in group E48 were significantly increased after exhaustive exercise(P<0.05), suggesting that autophagy increased in 48h after exhaustive exercise. (2) Compared with group C, p62mRNA and Lamp-2 mRNA levels were significantly increased immediately after blunt trauma(P<0.05) and decreased significantly in 48h after blunt trauma(P<0.05), suggesting that autophagy activity was enhanced immediately after blunt trauma and decreased in 48h after injury. Conclusions: Generally, there were differences at each recovery phase between blunt trauma and exhausted exercise models, and the basal autophagy factors and mitochondrial autophagy factors were also inconsistent. Basal autophagy factors p62 and Lamp-2 increased significantly 48 hours after eccentric exhaustive exercise and immediately after blunt trauma. Mitochondrial autophagy factor BNIP3 did not increase after exhaustive exercise and blunt trauma, but NIX only increased after exhaustive exercise. Its molecular mechanism needs to be further studied. Level of Evidence III; Therapeutic Studies Investigating the Results of Treatment.

RESUMEN Objetivo: Estudiar los cambios temporales de los factores relacionados con la autofagia en el músculo esquelético de ratas tras el ejercicio exhaustivo y el traumatismo contuso. Métodos: Se dividieron 42 ratas SD macho en 7 grupos con 6 ratas en cada grupo: grupo de control silencioso (C), inmediatamente después del ejercicio exhaustivo (E0), 24 horas después del ejercicio exhaustivo (E24), 48 horas después del ejercicio exhaustivo (E48), inmediatamente después de un traumatismo contuso (D0), 24 horas después de un traumatismo contuso (D24), 48 horas después de un traumatismo contuso (D48). Todos los grupos de ratas fueron sacrificados y rotulados, respectivamente, en diferentes momentos especificados anteriormente, y se extrajo el músculo gastrocnemio derecho, dividido en dos partes, una para los ARNm Lamp-2, BNIP3 y NIX mediante PCR cuantitativa fluorescente en tiempo real, y la otra para la proteína p62 mediante Western blotting. Resultados: (1) En comparación con el grupo C, los niveles de ARNm de p62, Lamp-2 y NIX en el grupo E48 aumentaron significativamente tras el ejercicio exhaustivo (P<0,05), lo que sugiere que la autofagia aumentó en las 48 horas posteriores al ejercicio exhaustivo. (2) En comparación con el grupo C, los niveles de ARNm de p62 ARNm y Lamp-2 aumentaron significativamente inmediatamente después del traumatismo contuso (P<0,05) y disminuyeron significativamente a las 48 horas después del traumatismo contuso (P<0,05), lo que sugiere que la actividad de autofagia aumentó inmediatamente después del traumatismo contuso y disminuyó a las 48 horas después de la lesión. Conclusión: En general, hubo diferencias en cada fase de recuperación entre los modelos de traumatismo contuso y ejercicio exhaustivo, y los factores de autofagia basal y los factores de autofagia mitocondrial también fueron inconsistentes. Los factores de autofagia basal p62 y Lamp-2 aumentaron significativamente 48 horas después del ejercicio excéntrico exhaustivo e inmediatamente después del traumatismo contuso. El factor de autofagia mitocondrial BNIP3 no aumentó tras el ejercicio exhaustivo y el traumatismo contuso, pero NIX sólo aumentó tras el ejercicio exhaustivo. Su mecanismo molecular debe investigarse con más detalle. Nivel de Evidencia III; Estudios Terapéuticos que Investigan los Resultados del Tratamiento.

RESUMO Objetivo: Estudar as alterações temporais dos fatores relacionados à autofagia no músculo esquelético de ratos após exercício exaustivo e trauma contuso. Métodos: Quarenta e dois ratos machos SD foram divididos em 7 grupos com 6 ratos em cada grupo: Grupo de controle silencioso (C), imediatamente após o exercício exaustivo (E0), 24 horas após o exercício exaustivo (E24), 48 horas após o exercício exaustivo (E48), imediatamente após o trauma contuso (D0), 24 horas após o trauma contuso (D24), 48 horas após o trauma contuso (D48). Todos os grupos de ratos foram mortos e rotulados, respectivamente, em diferentes momentos especificados acima, e o músculo gastrocnêmio direito foi retirado, dividido em duas partes, uma para mRNAs de Lamp-2, BNIP3 e NIX por PCR quantitativo fluorescente em tempo real, e a outra para a proteína p62 por imunotransferência. Resultados: (1) Em comparação com o grupo C, os níveis de mRNA de p62, Lamp-2 e NIX no grupo E48 aumentaram significativamente após o exercício exaustivo (P<0,05), sugerindo que a autofagia aumentou em 48 horas após o exercício exaustivo. (2) Em comparação com o grupo C, os níveis de mRNA de p62mRNA e Lamp-2 foram significativamente aumentados imediatamente após o trauma contuso (P<0,05) e diminuíram significativamente em 48 horas após o trauma contuso (P<0,05), sugerindo que a atividade de autofagia foi aumentada imediatamente após o trauma contuso e diminuiu em 48 horas após a lesão. Conclusão: Houve, via de regra, diferenças em cada fase de recuperação entre os modelos de trauma contuso e de exercício exaustivo, sendo que os fatores de autofagia basal e os fatores de autofagia mitocondrial também foram inconsistentes. Os fatores de autofagia basal p62 e Lamp-2 aumentaram significativamente 48 horas após o exercício excêntrico exaustivo e imediatamente após o trauma contuso. O fator de autofagia mitocondrial BNIP3 não aumentou após o exercício exaustivo e o trauma contuso, mas o NIX aumentou somente após o exercício exaustivo. Seu mecanismo molecular precisa ser investigado com mais detalhes. Nível de Evidência III; Estudos Terapêuticos que Investigam os Resultados do Tratamento.

Analysis of color stability and degree of conversion of different types of resin composites

Abstract Resin composites containing surface pre-reacted glass (S-PRG) have been introduced to reduce demineralization and improve remineralization of the tooth structure. However, water diffusion within the material is necessary for its action, which can impair its overall physicomechanical properties over time, including color stability. This study aimed to evaluate the color stability and related degree of conversion (DC) of four resin composites. Discs (6 x 4 mm, n = 5/group) of microhybrid (MH), nanofilled (NF), nanohybrid (NH), and S-PRG-based nanohybrid (S-PRG-NH) composites with two opacities (A2/A2E and A2O/A2D) were prepared. Color (CIELab and CIEDE2000) was evaluated with a spectrophotometer after aging in grape juice (2 x 10 min/10mL/7days). The DC was analyzed by using Fourier transform infrared spectroscopy before and after light-curing. Data were statistically analyzed by using two-way analysis of variance and post-hoc least significant difference tests (p<0.05). In the color stability analysis, the interaction between filler type and opacity was significant (CIELab, p = 0.0015; CIEDE2000, p = 0.0026). NH presented the highest color stability, which did not differ from that of MH. The greatest color alteration was observed for S-PRG-NH. S-PRG fillers also influenced DC (p < 0.05). The nanohybrid resin composite presented favorable overall performance, which is likely related to its more stable organic content. Notwithstanding the benefits of using S-PRG-based nanohybrid resins, mostly in aesthetic procedures, professionals should consider the susceptibility of such resins to color alteration, probably due to the water-based bioactive mechanism of action.

Development and internal validation of a clinical prediction model for spontaneous abortion risk in early pregnancy

Abstract Objective: This study aimed to develop and internally validate a prediction model for estimating the risk of spontaneous abortion in early pregnancy. Methods: This prospective cohort study included 9,895 pregnant women who received prenatal care at a maternal health facility in China from January 2021 to December 2022. Data on demographics, medical history, lifestyle factors, and mental health were collected. A multivariable logistic regression analysis was performed to develop the prediction model with spontaneous abortion as the outcome. The model was internally validated using bootstrapping techniques, and its discrimination and calibration were assessed. Results: The spontaneous abortion rate was 5.95% (589/9,895) 1. The final prediction model included nine variables: maternal age, history of embryonic arrest, thyroid dysfunction, polycystic ovary syndrome, assisted reproduction, exposure to pollution, recent home renovation, depression score, and stress score 1. The model showed good discrimination with a C-statistic of 0.88 (95% CI 0.87‒0.90) 1, and its calibration was adequate based on the Hosmer-Lemeshow test (p = 0.27). Conclusions: The prediction model demonstrated good performance in estimating spontaneous abortion risk in early pregnancy based on demographic, clinical, and psychosocial factors. Further external validation is recommended before clinical application.

Clinical and radiographic evaluation of Bio-Oss granules and Bio-Oss Collagen in the treatment of periodontal intrabony defects: a retrospective cohort study

Abstract Objective This retrospective study aimed to analyze the clinical efficacy of two regenerative surgical methods — Bio-Oss granules combined with barrier membranes and Bio-Oss Collagen alone — and to help clinicians achieve better periodontal regeneration outcomes in the specific periodontal condition. Methodology Patients who underwent periodontal regeneration surgery from January 2018 to April 2022 were retrospectively screened, and their clinical and radiographic outcomes at 6 months postoperatively were analyzed. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival recession (GR), distance from the cemento-enamel junction to the bottom of the bone defect (CEJ-BD), and depth of intrabony defects (INFRA) were recorded before the operation (T0) and 6 months after it (T1), and subsequently compared. Results In total, 143 patients were included — 77 were placed in the Bio-Oss group and 66 were placed in the Bio-Oss Collagen group. All indicators, including PD and CAL at T1, showed significant differences compared to baseline, for both groups (P<0.001). PD reduction was greater in the group receiving the Bio-Oss Collagen treatment (P=0.042). Furthermore, in cases when the baseline PD range was 7-11 mm and the age range was 35-50 years, PD reduction was more significant for patients receiving the Bio-Oss Collagen treatment (P=0.031, 0.023). A linear regression analysis indicated that postoperative PD and CAL were positively correlated with baseline values, and that the efficacy tended to decrease with increasing age. Conclusion Both the use of Bio-Oss Collagen alone and the use of Bio-Oss granules combined with barrier membranes resulted in significant effects in the treatment of periodontal intrabony defects. The Bio-Oss Collagen treatment generated more improvements in PD than the Bio-Oss granules combined with barrier membranes, particularly within the baseline PD range of 7-11 mm and the 35-50 years age group. Additionally, age was the main factor influencing the effectiveness of regenerative surgery for intrabony defects: older individuals exhibited fewer improvements.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment

Abstract Objective This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. Methods Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. Results Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. Conclusion Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.