Abstract Background and objective Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis and vascular lesions. Interstitial lung disease is an early complication of SSc and the main cause of death from SSc. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its role in systemic sclerosis-related interstitial lung disease (SSc-ILD) is unclear. The objective of our study was to explore the effect and mechanism of baricitinib in SSc-ILD. Methods We explored crosstalk between the JAK2 and TGF-β1 pathways. In vivo experiments, SSc-ILD mice model were constructed by subcutaneous injection of PBS or bleomycin (7.5 mg/kg) and intragastric administration of 0.5% CMC-Na or baricitinib (5 mg/kg) once every two days. We used ELISA, qRT-PCR, western blot and immunofluorescence staining to evaluate the degree of fibrosis. In vitro experiments, we used TGF-β1 and baricitinib to stimulate human fetal lung fibroblasts (HFLs) and assessed protein expression by western blot. Results The vivo experiments showed that baricitinib notably alleviated skin and lung fibrosis, decreased the concentration of pro-inflammatory factors and increased those of the anti-inflammatory factors. Baricitinib affected the expression of TGF-β1 and TβRI/II inhibitiing JAK2. In the vitro experiments, following the culture of HFLs with baricitinib or a STAT3 inhibitor for 48 h, the expression levels of TβRI/II decreased. Conversely, with successful inhibition of TGF-β receptors in HFLs, JAK2 protein expression decreased. Conclusions Baricitinib attenuated bleomycin-induced skin and lung fibrosis in SSc-ILD mice model by targeting JAK2 and regulating of the crosstalk between the JAK2 and TGF-β1 signaling pathways.

Abstract Gynostemma pentaphyllum is a functional food that is commercially available worldwide. Triterpenoid saponins are the main active components in Gynostemma pentaphyllum, which are usually hydrolyzed into triterpene sapogenins in organisms to play a pharmacological role. Gypensapogenin D is a triterpene sapogenins with the highest content in the hydrolysate of gypenoside. In addition, it was found that Gypensapogenin D had a certain inhibitory effect on α-glucosidase. In view of the poor solubility of Gypensapogenin D, which affects its bioavailability, Gypensapogenin D was prepared as a liposomal formulation in this paper, which provides valuable data for the later in-depth study and drug development and utilization of this compound. worldwide role gypenoside addition αglucosidase. αglucosidase α glucosidase. glucosidase α-glucosidase bioavailability paper indepth depth compound

Abstract Objective: To discover potentially modifiable perioperative predictors for renal replacement therapy (RRT) in patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: A cohort of 1773 consecutive cardiac surgery patients with postoperative acute kidney injury (AKI) from January 2013 to December 2015 were included retrospectively. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The primary outcome was CSA-AKI requiring renal replacement therapy (AKI-RRT). The initiation of RRT was based on clinical judgment regarding severe volume overload, metabolic abnormality (e.g., acidosis, hyperkalemia), and oliguria. Patients with AKI-RRT were matched 1:1 with patients without AKI-RRT by a propensity score, to exclude the influence of patients' demographics, comorbidities, and baseline renal function. Multivariable regression was performed to identify the predictors in the matched sample. Results: AKI-RRT occurred in 4.4% of the entire cohort (n=78/1773), with 28.2% of in-hospital mortality (n=22/78). With the propensity score, 78 pairs of patients were matched 1:1 and the variables found to be predictors of AKI-RRT included the contrast exposure within 3 days before surgery (odds ratio [OR]=2.932), central venous pressure (CVP) >10 mmHg on intensive care unit (ICU) admission (OR=1.646 per mmHg increase), and erythrocyte transfusions on the 1st day of surgery (OR=1.742 per unit increase). Conclusion: AKI-RRT is associated with high mortality. The potentially modifiable predictors found in this study require concern and interventions to prevent CSA-AKI patients from worsening prognosis.

SUMMARY: The nerve entry points (NEPs) cannot yet be accurately localized for the treatment of thigh adductor muscles spasticity in chemical neurolysis. The aim of this study was to identify the location and depth of the NEPs of thigh adductor muscles by spiral computed tomography (CT) and bony landmarks. Forty lower limbs of twenty adult cadavers were dissected in supine position. A curved line on skin surface from the tip of greater trochanter of femur to the center of pubic tubercle was designated as the horizontal reference line (H). Another curved line from the tip of great trochanter to the lateral epicondyle of femur was designated as the longitudinal reference line (L). Following dissection, the NEPs were labeled with barium sulfate, and their body surface projection points (P) were determined by spiral CT. Projection of NEP in the opposite direction was designated as P'. The percentage location of the intersections (PH and PL) of P with the H and L and the percentage depth of NEPs were determined with the Syngo system. The PH for the NEP of pectineus, gracilis, adductor longus, adductor brevis and adductor magnus muscles branch were located at 76.41±0.71 %, 93.85±2.07 %, 92.05±2.15 %, 80.75±1.20 % and 88.08±1.09 % of the H, respectively. The PLwere at 1.64±0.04 %, 29.89±1.90 %, 16.06±1.32 %, 11.66±0.11 % and 22.94±0.90 % of the L, respectively. The depth of NEP from P points were at 17.52±0.52 %, 38.38±2.75 %, 20.88±0.79 %, 20.35±0.82 % and 39.52±0.67 % of PP', respectively. These results help to carry out more precise localization of the NEPs. It should provide a novel anatomical guide for improving the efficacy and efficiency of chemical neurolysis in treating thigh adductor muscle spasticity.

RESUMEN: Aún no se pueden localizar con precisión los puntos de entrada del nervio (PEN) para el tratamiento de la espasticidad de los músculos aductores del muslo a través de la neurólisis química. El objetivo de este estudio fue identificar la ubicación y la profundidad de los PEN de los músculos aductores del muslo mediante tomografía computarizada espiral (TC) y puntos de referencia óseos. Se disecaron loa miembros inferiores de 20 cadáveres adultos en posición supina. Se trazó una línea curva en la superficie de la piel desdeel ápice del trocánter mayor del fémur hasta el centro del tubérculo púbico y se designó como línea de referencia horizontal (H). Otra línea curva desde el ápice del trocánter mayor hasta el epicóndilo lateral del fémur se designó como línea de referencia longitudinal (L). Después de la disección, los PEN se marcaron con sulfato de bario y sus puntos de proyección de la superficie del cuerpo (P) se determinaron mediante TC helicoidal. La proyección de PEN en la dirección opuesta se designó como P '. El porcentaje de ubicación de las intersecciones (PH y PL) de P con H y L y la profundidad porcentual de los PEN se determinaron con el sistema Syngo. Los PH para los PEN de los músculos pectineus, gracilis, adductor longus, aductor brevis y rama aductora del músculo aductor magnus se localizaron en 76,41±0,71 %, 93,85±2,07 %, 92,05±2,15 %, 80,75±1,20 % y 88,08±1,09 % de H, respectivamente. Los PL estuvieron en 1,64±0,04 %, 29,89±1,90 %, 16,06±1,32 %, 11,66±0,11 % y 22,94±0,90 % de la L, respectivamente. La profundidad de PEN de P puntos fue de 17,52±0,52 %, 38,38±2,75 %, 20,88±0,79 %, 20,35±0,82 % y 39,52±0,67 % de PP ', respectivamente. Estos resultados ayudan a realizar una localización más precisa de los PEN. Se debe proponer una nueva guía anatómica para mejorar la eficacia y la eficiencia de la neurólisis química en el tratamiento de la espasticidad del músculo aductor del muslo.