Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective To design and evaluate a dilation incision device capable of facilitating stable support and flexible adjustment during neurosurgical procedures.Methods The dilation incision device was composed of a support plate,an adjustment assembly,a brain support ring,a rotation assembly,an electric motor,an expansion assembly and a neck support ring.The support plate was made of high-strength stainless steel;the adjustment assembly was made up of a first screw,a lifting groove,a slide bar and a nut;the brain support ring was fixed to the adjustment assembly through a support rod,with an outer layer of medical-grade silicone and an inner layer of stainless steel skeleton;the rotation assembly connected the brain support ring with the expansion assembly and consisted of a rotating shaft,a connecting rod and a rotating lug;a high-precision direct current servo motor was selected for the device;the expansion assembly included a spring,an expansion plate and a moving plate,which realized auto expansion or contraction through spring pressure;the neck support ring had its outer layer made of flexible polyurethane foam and inner layer being a stainless steel skeleton.The device had its stability and safety evaluated by static and dynamic tests at different heights(50,100,150 mm)and angles(0°,30°,60°),which was compared with the traditional fixation device to verify its application effect.Results Static and dynamic tests indicated the device showed high stability and safety in different heights and angles,and gained advantages over the traditional device in stability,convenient operation and surgical field visualization.Conclusion The device developed meets the requirements of neurosurgical procedures,and enhances the safety and portability of neurosurgical procedures.[Chinese Medical Equipment Journal,2024,45(10):37-40]

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Gegen Qinlian decoction has a wide range of clinical applications. However, there is a lack of systematic quality evaluation methods to ensure the safety and effectiveness of Gegen Qinlian decoction in clinical use. The UHPLC fingerprint and multi-component determination method of Gegen Qinlian decoction were established to provide scientific basis for the quality control and evaluation of Gegen Qinlian decoction. The chromatography was performed on a ZORBAX Eclipse Plus-C₁₈ column (150 mm × 4.6 mm, 3.5 μm) with mobile phase consisted of acetonitrile (A) - 20 mmol·L^-1 ammonium acetate (containing 0.8% acetic acid and 0.5% triethylamine) (B) and gradient elution at a flow rate of 1.0 mL·min^-1. The column temperature was 25 ℃, the detection wavelength was 260 nm, the fingerprint of 10 batches of Gegen Qinlian decoction was determined, and the similarity evaluation system of TCM chromatographic fingerprint was used for comprehensive analysis, and 9 components were quantitatively analyzed. In the fingerprint study of Gegen Qinlian decoction, a total of 18 peaks were obtained, 12 of which were identified by reference substances. Moreover, the similarity of 10 batches of Gegen Qinlian decoction was good, and all of them were greater than 0.99. In the multi-component quantitative analysis, the linear relationship between the nine components and the peak area was good (r ≥ 0.999) in the corresponding mass concentration range. The average recovery rate was 94.4%-100.3%, and the RSD was 0.1%-1.4%. The fingerprint of Gegen Qinlian decoction was studied under the same wavelength, and the content of 9 main components were determined by our established method. The method has high sensitivity and strong specificity, which provided a comprehensive scientific basis for the comprehensive evaluation of the quality of Gegen Qinlian decoction.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Based on ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), a rapid and simultaneous quantitative method for the measurement of seven components (kinsenoside; rutin; kaempferol-3-O-rutinoside; quercimeritrin; narcissin; isorhamnetin-3-O-glucoside; quercetin) of A. roxburghii was established. The separation was performed over 8.0 minutes on a Waters Acquity UPLC BEH Shield RP18 (2.1 mm × 100 mm; 1.7 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.2 mL·min^-1; the column temperature was 30 ℃ and the injection volume was 2 μL. Electrospray spray ionization source (ESI source) was used for mass spectrometry, and positive and negative ion modes were detected at the same time. The results showed good linearity (R² ≥ 0.998 0), with good precision, repeatability and stability, and the average recovery was 97.71%-103.33%. Through cluster heat map and redundancy analysis, we found that kinsenoside was mainly distributed in stems, followed by leaves, and the lowest content in roots. The content of kinsenoside increased significantly in the stems of plants 6 months, but less change was evident in the roots and leaves. Flavonoids and flavonoid glycosides were mainly distributed in leaves. The UHPLC-MS/MS method established in this paper can be used for the quality control of A. roxburghii and provides a reference for establishing a more comprehensive quality detection method for this medicinal.

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.
Syringa ; Sesquiterpenes ; Terpenes ; Asthma ; Chromatography, Liquid

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.