Ethnopharmacological relevanceAlpinia officinarum Hance (A. officinarum), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A. officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A. officinarum, has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated.Aim of the studyThis investigation aims to elucidate the anti-HCC effects of kaempferol derived from A. officinarum and to delve into its underlying mechanistic pathways.Materials and MethodsUsing ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum. HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A. officinarum. The cytotoxicity and proliferation of kaempferol and A. officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples.ResultsUPLC-MS/MS was employed to detect five active compounds in A. officinarum, such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A. officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC.ConclusionsCollectively, our results revealed that kaempferol from A. officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.

Ethnopharmacological relevance: Alpinia officinarum Hance is a perennial natural medicine herbivorous plant, has been used in the management of treat stomach pain and diabetes, it is abundantly cultivated in Qiongzhong, Baisha and other places. P. cablin (Blanco) Benth, one of the most important traditional Chinese plants, which plays functions in antioxidant and gastrointestinal regulation, has been extensively planted in Hainan, Guangdong and other regions. Aim of the study: In this study, we investigated the role and underlying molecular mechanism of AP on diabetic gastroparesis (DGP) in vitro and in vivo. Materials and methods: In this study, using ultra -high performance liquid chromatography -mass spectrometry/ mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum Hance-P. cablin (Blanco) Benth drug pair (AP). Molecular docking were utilized to explore the potential mechanism of AP treatment of DGP. In in vitro assays, gastric smooth muscle cells (GSMCs) were treated with 35 mM glucose to promote apoptosis and construct the DGP model, which was treated with different concentrations of AP. Furthermore, transfection technology was used to overexpress RAGE in GSMCs and elucidate the underlying mechanisms of alleviation of DGP by AP. Results: Using UPLC-MS/MS analysis, nine components of AP were identified. We found that AP effectively blocked the increase in apoptosis, oxidative stress, and intracellular Ca2+ concentrations. For in vivo experiments, mice were fed with a high -fat irregular diet to construct DGP model, and AP was co -administered via oral gavage daily to prevent the development of DGP. Compared with DGP mice, AP significantly decreased fasting blood glucose levels and increased gastric emptying levels. Consistent with in vitro experiments, AP also considerably decreased the increase in oxidative stress in DGP mice. Mechanistically, AP alleviates apoptosis and DGP by decreasing oxidative stress and intracellular Ca2+ concentrations via the inhibition of the AGE/RAGE axis. Conclusions: Collectively, this study has established that AP can improve DGP, and the mechanism may be related to the inhibition the AGE/RAGE axis to mitigate apoptosis and DGP. To summarize, this study provides a novel supplementary strategy for DGP treatment.

Salvia MiltiorrhizaBunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1% in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.

Galangin, a flavonoid compound, is derived from Alpinia officinarum Hance. Previous studies have shown that galangin can inhibit the proliferation of hepatocellular carcinoma (HCC), but its mechanism is still unclear. This study aims to investigate the potential targets and molecular mechanisms of galangin on HCC through network pharmacology, bioinformatics, molecular docking, and experimental in vitro validation. In this study, network pharmacology was used to investigate the targets and mechanisms of galangin in the treatment of HCC. AutoDockTools software was used to simulate and calculate the binding of galangin to its core targets. GO and KEGG enrichment analyses were conducted in the DAVID database to explore the main biological functions and signaling pathways impacted by galangin intervention. In addition, bioinformatics was applied to examine the correlation between the differential expressions of the anti-HCC core targets of galangin and the survival of patients with HCC. Finally, the findings obtained from network pharmacology and bioinformatics were verified in cell experiments. A total of 67 overlapping target genes of galangin and HCC were identified. Through the analysis of the protein-protein interaction (PPI) network, 10 hub genes with the highest degree of freedom were identified, including SRC, ESR1, MMP9, CDK4, CCNB1, MMP2, CDK2, CDK1, CHK1, and PLK1. These genes were found to be closely related to the degradation of the extracellular matrix, signal transduction, and the cell cycle. GO and KEGG enrichment analyses revealed that galangin exerts an anti-HCC role by affecting various signaling pathways, including the cell cycle, pathways in cancer, and the PI3K-Akt signaling pathway. The results of molecular docking indicated a significant interaction between galangin and CCNB1, CDK4, CDK1, and PLK1. Bioinformatics analysis revealed that CCNB1, CDK4, CDK1, and PLK1 were upregulated in the liver of patients with HCC at both the mRNA and protein levels. Flow cytometry analysis showed that galangin induced G0/G1 phase arrest and cell apoptosis in HepG2 and Huh7 cells. Additionally, galangin suppressed the expression of key proteins and mRNAs involved in the cell cycle pathway. These results suggest that galangin inhibits the growth of HCC cells by arresting the cell cycle at the G0/G1 phase.

This study explored the mechanism of microRNA (miR)-30a in the activation of hepatic stellate cells (HSCs) to deepen the understanding of the pathogenesis of liver fibrosis. Subsequent to knockdown and ectopic experiments, HSCs were induced with 10 ng/mL transforming growth factor (TGF)-β1 to inspect the role of the miR-30a/TGF-β receptor 1 (TGFBR1) axis in HSC proliferation and activation. qRT-PCR was utilized to examine TGFBR1 mRNA and miR-30a expression and western blot to test TGFBR1, alpha smooth muscle actin (α-SMA), Collagen I and mothers against DPP homolog 2/3 (Smad2/3) protein expression. The fluorescence intensity of α-SMA was measured with immunofluorescence staining. The interaction of TGFBR1 with miR-30a was tested with a dual-luciferase reporter assay. TGF-β1 treated HSCs had upregulated expressions of α-SMA and Collagen I. In addition, downregulated miR-30a, upregulated TGFBR1 and activated TGF-β1/Smad2/3 pathway were found in activated HSCs. Upregulation of miR-30a or downregulation of TGFBR1 suppressed the activation and growth of HSCs. miR-30a repression activated the TGF-β1/Smad2/3 pathway and promoted HSC proliferation and activation, while suppression of TGFBR1 revered these effects. miR-30a was an upstream regulatory factor of TGFBR1. miR-30a blocks the TGF-β1/Smad2/3 pathway to inhibit HSC activation against liver fibrosis by targeting TGFBR1.

BACKGROUND:Regorafenib, a multi-targeted kinase inhibitor, has been used in the treatment of Hepatocellular carcinoma (HCC). The purpose of this study is to investigate the mechanism of Regorafenib in HCC.METHODS:Regorafenib's impact on the sensitivity of HCC cells was assessed using CCK8. Differential gene expression analysis was performed by conducting mRNA sequencing after treatment with Regorafenib. The m6A methylation status of CHOP and differential expression of m6A methylation-related proteins were assessed by RIP and Western Blot. To explore the molecular mechanisms involved in the therapeutic effects of Regorafenib in HCC and the impact of METTL14 and CHOP on Regorafenib treatment, we employed shRNA/overexpression approaches to transfect METTL14 and CHOP genes, as well as conducted in vivo experiments.RESULTS:Treatment with Regorafenib led to a notable decrease in viability and proliferation of SK-Hep-1 and HCC-LM3 cells. The expression level of CHOP was upregulated after Regorafenib intervention, and CHOP underwent m6A methylation. Among the m6A methylation-related proteins, METTL14 exhibited the most significant downregulation. Mechanistic studies revealed that Regorafenib regulated the cell cycle arrest in HCC through METTL14-mediated modulation of CHOP, and the METTL14/CHOP axis affected the sensitivity of HCC to Regorafenib. In vivo, CHOP enhanced the anticancer effect of Regorafenib.CONCLUSION:The inhibition of HCC development by Regorafenib is attributed to its modulation of m6A expression of CHOP, mediated by METTL14, and the METTL14/CHOP axis enhances the sensitivity of HCC to Regorafenib. These findings provide insights into the treatment of HCC and the issue of drug resistance to Regorafenib.

Background Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, there have been no patients with liver cancer who have undergone ABO-incompatible (ABOi) LT after treatment with the programmed cell death protein 1 (PD-1) inhibitor reported in the literature. Case presentation A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. Conclusion We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1→4)-α-D-GalpA and (1→2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH.

目的 探讨肝移植受者术后单用霉酚酸(mycophenolic acid,MPA)类药物的远期疗效.方法 回顾性分析2002年9月至2021年8月期间解放军总医院第三医学中心30例肝移植受者临床资料,上述病例从钙调磷酸酶抑制剂(calcineurin inhibitor,CNI)方案因肾毒性转换为单药霉酚酸类药物免CNI类方案,并对转换前后肝功能、肾功能以及其不良反应进行对比分析,随访周期为2年.结果 转换后1年与转换后2年的肌酐(creatinine,Cr)水平分别为(83.5±24.3)μmol/L、(74.2±15.9)μmol/L.估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)分别为(77.7±9.1)ml/min、(86.1±6.5)ml/min.与转换前比较,Cr水平明显降低(P＜0.05),eGFR水平得到明显提高(P＜0.05).丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBil)水平前后无明显变化(均P＞0.05).结论 肝移植远期的受者霉酚酸类药物单药维持,其安全性值得肯定,无明显不良反应,且其肾功能水平可从免CNI抗排斥方案中获益.

(4E)-7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (DPHB) derived from A. officinarum Hance has been reported to exert anti-inflammatory and anti-insulin resistance (IR) effects. We explored the molecular mechanism of DPHB ameliorating IR through network pharmacological prediction and in vitro analysis. The PI3K/AKT and TNF signaling pathways are the core pathways for DPHB to exert anti-IR, and the key proteins of this pathway were confirmed by molecular docking. In the IR-3T3-L1 adipocyte model, DPHB significantly promoted glucose uptake and the glucose transporter type 4 (GLUT4) translocation. In addition, DPHB significantly improved lipid accumulation, triglyceride content, and the mRNA expression of key adipokines [such as peroxisome proliferator-activated receptors-gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1)]. DPHB inhibited the protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and phosphorylated nuclear factor-κB (NF-kB), as well as promoted the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylated PI3K, and phosphorylated AKT. More interestingly, validation of the PI3K inhibitor LY294002 revealed that these changes were dependent on the activation of PI3K. Our cumulative findings thereby validate the potential of DPHB to alleviate and treat IR and the related diseases by regulating the PI3K/AKT and TNF-α signaling pathways.

目的 应用声辐射力脉冲(ARFI)技术检测移植肝组织剪切波速度,探讨移植肝组织硬度与肝功能的关系.方法 回顾性分析146例肝移植术后患者临床资料,肝移植受者均进行了 ARFI检查,测量移植肝组织的剪切波值,并进行分组分析.结果 ①酶学正常组和酶学增高组以及胆红素正常组和增高组的剪切波值分别为(1.23±0.30)m/s和(1.41±0.43)m/s,(1.25±0.32)m/s和(1.48±0.47)m/s,差异均具有统计学意义.②各酶学指标及胆红素指标分别与移植肝剪切波值呈正相关,相关系数为0.621、0.404、0.482、0.570和0.573,P＜0.05.③肝移植术后1年以上和1年以内组的剪切波值分别为(1.24±0.37)m/s和(1.59±0.53)m/s,差异具有统计学意义;肝移植术后≤7d组的剪切波值为(1.95±0.69)m/s,明显高于其他时间段组的剪切波值.结论 移植肝组织硬度升高与肝脏肝功能异常相关,剪切波速度在评估移植肝功能时具有重要临床价值.

Purpose:This study aimed to investigate the application of color Doppler ultrasound (CDU) and contrast-enhanced ultrasound (CEU) in the early diagnosis of arterial steal syndrome (ASS) after orthotopic liver transplantation (OLT).Patients and Methods:A total of 1827 patients received OLT in our department between January 2007 and December 2021, and CDU and CEU were performed after surgery. Ultrasonographic data were collected and further analyzed. ASS was confirmed by digital subtraction angiography (DSA), and the use of splenic artery embolization was dependent on the DSA findings and clinical conditions. The ultrasonographic data were collected before and after embolization.Results:ASS was found in 23 patients (23/1827; 1.26%). CDU: the portal vein velocity was higher than normal in 17 patients (52.83±21.74 cm/s); the hepatic artery flow signals disappeared in 7 patients; the hepatic artery velocity was 13.57±5.85 cm/s in 16 patients. In 23 patients, the spleen artery velocity was 170.12±32.04 cm/s. CEU: the hepatic artery was observed in 7 patients without hepatic artery flow signals on CDU; in 23 patients, the contrast agent reached the portal vein at the presence of contrast in the hepatic artery or earlier (difference: 2.21±1.09 s). Splenic artery embolization was done in 17 of 23 patients with ASS. The hepatic artery flow velocity, hepatic artery resistance index, splenic artery velocity and time to the presence of contrast were significantly improved after embolization (P<0.05).Conclusion:CDU and CEU are the preferred, effective tools in the diagnosis of ASS. Reduced peak hepatic artery velocity, increased spleen artery velocity and reduced time difference in the contrast reaching the portal vein and hepatic artery are indicative of ASS.

目的 探讨超声造影(CEUS)在儿童肝移植术后肝动脉血栓(HAT)中的临床应用价值.方法 回顾性分析126例儿童肝移植受者的临床资料,总结儿童肝移植术后HAT发生情况,比较HAT的彩色多普勒超声和CEUS表现.结果 彩色多普勒超声高度怀疑HAT者17例,CEUS诊断HAT者9例,其中CEUS提示HAT的9例受者均经CT血管造影(CTA)或手术证实诊断.HAT的CEUS表现为肝动脉在动脉期乃至门静脉期在门静脉周围未见显影,4例HAT患者发生肝细胞坏死,CEUS表现为肝内造影剂无灌注.结论 CEUS在儿童肝移植术后HAT的诊断中有较高的临床应用价值,与传统CTA相比优势明显,可以在临床广泛推广.

ETHNOPHARMACOLOGICAL RELEVANCE Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). AIM OF THE STUDY Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. MATERIALS AND METHODS HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3β. RESULTS DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. CONCLUSIONS DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.

目的 探讨血清C反应蛋白(C-reactive protein,CRP)预测肝移植术后肝癌复发的价值.方法 回顾性分析本中心2013年3月至2019年3月65例肝癌行肝移植术患者的临床资料,阳性组(CRP≥8 mg/L),阴性组(CRP<8 mg/L),对搜集的相关数据进行统计分析.结果 65例患者中,45例(75.0％)符合米兰标准,32例(49.2％)移植前治疗史.阳性组30例(46.2％),在多变量分析中血清CRP≥8 mg/L是肝癌复发的独立危险因素,两组2年复发率分别为74.3％和14.8％(HR=10.36,95％CI=3.89～27.61;P=0.000).阳性组与阴性组的患者总体生存期亦具有明显统计学差异(P=0.000).结论 术前CRP检测可预测肝移植术后肝癌复发并提示患者预后.

Objective:To analyze the quantitative parameters of hepatic microperfusion by contrast-enhanced ultrasound in rabbits with brain death, in order to explore a new method for evaluating the donor liver of individuals with brain death.Methods:Rabbits with brain death (n=15) were prepared by surgery and maintained for 8 hours, and rabbits undergoing sham operation were used as controls (n=5). Contrast-enhanced ultrasonography and quantitative analysis of microblood flow were performed in the two groups at 0 h, 4 h, and 8 h after modeling. The quantitative parameters included area under the curve (AUC), peak intensity (PI), peak time (Tp), and average transit time (MTT). The t-test was used to compare the differences of liver contrast-enhanced ultrasound quantitative parameters AUC, PI, Tp, and MTT between the two groups at different time points. Liver function and pathology were evaluated at the same time.Results:Under the condition of brain death, the AUC values of 13 rabbits (13/15, 86.7%) showed a gradually downward trend, and the PI values of 15 rabbits (15/15, 100%) showed a gradually downward trend. At 0 h after modeling, the PI value of the brain death group was significantly higher than that of the control group [(66.1±9.1)% vs (54.9±7.3)%, t=-11.276, P=0.032], and at 8 h, the PI value of the brain death group was significantly lower than that of the control group [(44.9±10.3)% vs (68.5±2.9)%, t=-10.395, P=0.001]; at 4 h, there was no significant difference in the PI value between the two groups (P＞0.05). Eight hours after modeling, the AUC value of the brain death group was significantly lower than that of the control group [(2591.7 ±732.7)%s vs (4520.0 ±182.8)%s, t=-18.762, P＜0.001], but there was no significant difference at 0 h and 4 h (P＞0.05). At 0 h, 4 h, and 8 h after modeling, there was no significant difference in the Tp scores and MTT values between the two groups (P＞0.05).Conclusion:The amount of hepatic microperfusion decreases in rabbits with brain death, and contrast-enhanced ultrasound can be used as an effective method to evaluate the donor liver of individuals with brain death.

目的 对比研究脑死亡(brain death,BD)供肝与健康成人肝脏剪切波速度(shear wave velocity,SWV)差异,探讨剪切波弹性成像在BD供肝质量评估中的应用价值.方法 回顾性分析我院器官移植中心2018年3月—2018年6月脑死亡器官捐献供肝50例作为脑死亡组,50例年龄相匹配的正常人作为对照组.应用西门子公司ACUSON S2000/S3000超声仪,配备声辐射力脉冲(acoustic radiation force impulse,ARFI)成像技术,测量BD供肝组和对照组的肝脏SWV值,同时对BD供肝进行肝功能和病理检查,并进行统计分析.结果 BD供肝组与对照组的SWV值分别为(1.53±0.37)m/s、(1.14±0.06)m/s,两组比较差异有统计学意义(P=0.000).50例BD供肝,其中39例(39/50,78％)出现一项或多项肝功能指标异常,37例(37/50,74％)供肝病理有轻微异常.BD供肝受者术后早期肝功能恢复延迟11例(11/50,22％),早期肝功能恢复正常39例(39/50,78％).结论 剪切波弹性成像技术可以量化供肝硬度值,在BD供肝质量评估中具有一定的应用价值,可以作为辅助评估BD供肝质量的超声新技术.