The incidence and mortality rates of hepatocellular carcinoma(HCC)remain high in China,and the application of surgical resection is often limited due to the fact that most patients are in the advanced stage at the time of confirmed diagnosis.This article reviews commonly used advanced locoregional therapies for HCC and the advances in mainstream techniques such as local ablation(radiofrequency ablation,microwave ablation,irreversible electroporation,and cryoablation),intravascular intervention(transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,and Y90 hepatic arterial infusion chemotherapy),and radiotherapy(CyberKnife,proton therapy,and heavy-ion therapy),and a multidimensional decision-making framework is constructed for HCC locoregional therapy by comparing treatment principles,indications,limitations,and clinical data of these techniques.This article aims to provide evidence-based support for persistent dilemmas in clinical decision-making,promote the role of locoregional therapies in clinical practice,and propose the directions for future research and clinical application.This article also establishes a comprehensive clinical roadmap for HCC locoregional therapy,which helps to address current challenges regarding technique selection and delineate future directions for innovation,in order to reshape the treatment of HCC through technological integration and paradigm innovation.

Objective:To explore the expression changes of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) signaling pathway of dorsal root ganglia (DRG) in incisional rat remifentanil-induced hyperalgesia and its effect on the expression of membrane delta opioid receptor (DOR).Methods:A total of 48 SPF male SD rats were randomly divided into 6 groups based on body weight matching, with 8 in each group, which were control group (infusion of 0.9% NaCl solution via the tail vein), incision pain group (incision pain model established using the Brennan method), remifentanil group (infusion of remifentanil via the tail vein), incision pain+ remifentanil model group (incision pain model established using the Brennan method, followed by infusion of remifentanil via the tail vein), NGF group and TrkA inhibitor group(established incision pain+ remifentanil model after intrathecal injection of NGF (0.06 μg/g) or K252a (0.3 μg/g, TrkA inhibitor)). Mechanical paw withdrawal threshold (PWT) was used to assess pain sensitivity in rats. Western blot was employed to measure the expression of NGF, TrkA, and the total DOR(tDOR) and the membrane DOR(mDOR) in DRG tissues. Immunoelectron microscopy was used to detect subcellular DOR expression in DRG. Data were processed using SPSS 24.0 software. Multiple comparisons among groups were conducted by repeated measures ANOVA or one-way ANOVA, and post-hoc comparisons were performed using the Bonferroni test.Results:(1) The results of pain behavior showed that there was a significant interaction effect between time and group in the comparison of PWT among the six groups of rats before and after intervention ( F=345.817, P<0.001). At each time point after intervention, the PWTs of the incision pain+ remifentanil group were lower than those of the incision pain group and remifentanil group, the PWTs of the NGF group were lower than those of the incision pain+ remifentanil group, and the PWTs of the TrkA inhibitor group were higher than those of the incision pain+ remifentanil group and NGF group (all P<0.05). (2)The Western blot results showed that there were statistically significant differences in the relative levels of NGF, TrkA, and mDOR in the DRG tissues of the six groups of rats ( F=156.2, 163.8, 421.2, all P<0.001). The levels of NGF, TrkA, and mDOR proteins in the incision pain+ remifentanil group (1.45±0.07, 1.46±0.04, 3.01±0.20) were higher than those in the incision pain group (1.25±0.05, 1.24±0.04, 1.84±0.05) and remifentanil group (1.24±0.04, 1.26±0.03, 1.84±0.04) (all P<0.05). The levels of NGF, TrkA, and mDOR in the NGF group (1.57±0.03, 1.58±0.07, 3.74±0.25) were higher than those in the incision pain+ remifentanil group (all P<0.05). The relative expression levels of TrkA, and mDOR in the TrkA inhibitor group (1.25±0.04, 1.68±0.07) were lower than those in the incision pain+ remifentanil group and the NGF group (all P<0.05). (3)The results of immunoelectron microscopy showed that there were statistically significant differences in the localization of DOR in the cell membrane, subcellular sites of synthesis pathways, and subcellular localization of degradation pathways among the six groups of rat DRG tissues ( F=140.3, 60.63, 60.28, all P<0.01). The DOR of the synthesis pathway of incision pain+ remifentanil group was higher than that of the incision pain group and remifentanil group, while the DOR of the synthesis pathway of NGF was higher than that of the incision pain+ remifentanil group.The DOR of the synthesis pathway of TrkA inhibitor group was lower than that of the incision pain+ remifentanil group and NGF group (both P<0.05). The DOR of the degradation pathway in the incision pain+ remifentanil group was lower than that in the incision pain group and remifentanil group, the DOR of the degradation pathway in the NGF group was lower than that in the incision pain+ remifentanil group, and the DOR of the degradation pathway in the TrkA inhibitor group was higher than that in the incision pain+ remifentanil group and NGF group (both P<0.05). Conclusion:The NGF/TrkA signaling pathway is involved in rat incisional pain-remifentanil hyperalgesia by upregulating the delta opioid receptor of the dorsal root ganglia.

Objective:To explore the expression changes of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) signaling pathway of dorsal root ganglia (DRG) in incisional rat remifentanil-induced hyperalgesia and its effect on the expression of membrane delta opioid receptor (DOR).Methods:A total of 48 SPF male SD rats were randomly divided into 6 groups based on body weight matching, with 8 in each group, which were control group (infusion of 0.9% NaCl solution via the tail vein), incision pain group (incision pain model established using the Brennan method), remifentanil group (infusion of remifentanil via the tail vein), incision pain+ remifentanil model group (incision pain model established using the Brennan method, followed by infusion of remifentanil via the tail vein), NGF group and TrkA inhibitor group(established incision pain+ remifentanil model after intrathecal injection of NGF (0.06 μg/g) or K252a (0.3 μg/g, TrkA inhibitor)). Mechanical paw withdrawal threshold (PWT) was used to assess pain sensitivity in rats. Western blot was employed to measure the expression of NGF, TrkA, and the total DOR(tDOR) and the membrane DOR(mDOR) in DRG tissues. Immunoelectron microscopy was used to detect subcellular DOR expression in DRG. Data were processed using SPSS 24.0 software. Multiple comparisons among groups were conducted by repeated measures ANOVA or one-way ANOVA, and post-hoc comparisons were performed using the Bonferroni test.Results:(1) The results of pain behavior showed that there was a significant interaction effect between time and group in the comparison of PWT among the six groups of rats before and after intervention ( F=345.817, P<0.001). At each time point after intervention, the PWTs of the incision pain+ remifentanil group were lower than those of the incision pain group and remifentanil group, the PWTs of the NGF group were lower than those of the incision pain+ remifentanil group, and the PWTs of the TrkA inhibitor group were higher than those of the incision pain+ remifentanil group and NGF group (all P<0.05). (2)The Western blot results showed that there were statistically significant differences in the relative levels of NGF, TrkA, and mDOR in the DRG tissues of the six groups of rats ( F=156.2, 163.8, 421.2, all P<0.001). The levels of NGF, TrkA, and mDOR proteins in the incision pain+ remifentanil group (1.45±0.07, 1.46±0.04, 3.01±0.20) were higher than those in the incision pain group (1.25±0.05, 1.24±0.04, 1.84±0.05) and remifentanil group (1.24±0.04, 1.26±0.03, 1.84±0.04) (all P<0.05). The levels of NGF, TrkA, and mDOR in the NGF group (1.57±0.03, 1.58±0.07, 3.74±0.25) were higher than those in the incision pain+ remifentanil group (all P<0.05). The relative expression levels of TrkA, and mDOR in the TrkA inhibitor group (1.25±0.04, 1.68±0.07) were lower than those in the incision pain+ remifentanil group and the NGF group (all P<0.05). (3)The results of immunoelectron microscopy showed that there were statistically significant differences in the localization of DOR in the cell membrane, subcellular sites of synthesis pathways, and subcellular localization of degradation pathways among the six groups of rat DRG tissues ( F=140.3, 60.63, 60.28, all P<0.01). The DOR of the synthesis pathway of incision pain+ remifentanil group was higher than that of the incision pain group and remifentanil group, while the DOR of the synthesis pathway of NGF was higher than that of the incision pain+ remifentanil group.The DOR of the synthesis pathway of TrkA inhibitor group was lower than that of the incision pain+ remifentanil group and NGF group (both P<0.05). The DOR of the degradation pathway in the incision pain+ remifentanil group was lower than that in the incision pain group and remifentanil group, the DOR of the degradation pathway in the NGF group was lower than that in the incision pain+ remifentanil group, and the DOR of the degradation pathway in the TrkA inhibitor group was higher than that in the incision pain+ remifentanil group and NGF group (both P<0.05). Conclusion:The NGF/TrkA signaling pathway is involved in rat incisional pain-remifentanil hyperalgesia by upregulating the delta opioid receptor of the dorsal root ganglia.

The incidence and mortality rates of hepatocellular carcinoma(HCC)remain high in China,and the application of surgical resection is often limited due to the fact that most patients are in the advanced stage at the time of confirmed diagnosis.This article reviews commonly used advanced locoregional therapies for HCC and the advances in mainstream techniques such as local ablation(radiofrequency ablation,microwave ablation,irreversible electroporation,and cryoablation),intravascular intervention(transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,and Y90 hepatic arterial infusion chemotherapy),and radiotherapy(CyberKnife,proton therapy,and heavy-ion therapy),and a multidimensional decision-making framework is constructed for HCC locoregional therapy by comparing treatment principles,indications,limitations,and clinical data of these techniques.This article aims to provide evidence-based support for persistent dilemmas in clinical decision-making,promote the role of locoregional therapies in clinical practice,and propose the directions for future research and clinical application.This article also establishes a comprehensive clinical roadmap for HCC locoregional therapy,which helps to address current challenges regarding technique selection and delineate future directions for innovation,in order to reshape the treatment of HCC through technological integration and paradigm innovation.

Objective:To review the patients with supramitral ring (SMR) and summary echocardiographic features and operative prognosis in these patients.Methods:Clinical and echocardiographic data of 53 patients with SMR treated in Fuwai Hospital from Jan 2016 to Jan 2020 were reviewed. Patients were divided into simple group( n=28) and complex group( n=25) based on mitral apparatus normal or not. The echocardiographic characteristics, morphology of the rings, procedure′s results and follow-up data were recorded and assessed. Results:There was no significant difference in age, peak and mean mitral value(MV) gradient before surgery between the two groups (all P>0.05). Patients with mitral regurgitation and left outflow tract obstruction in complex group were more than in simple group (all P<0.05). All patients underwent cardiac operation. The average follow-up were(14.69±11.14)months. The overall missed diagnosis was 13%. The missed diagnosis rate in complex group was higher(20% vs 7%). The peak and mean MV gradient in all patients after surgery were reduced (all P<0.05), but the gradients in complex group were higher than simple group(all P<0.05). Restensis occurred in 3 patients in each group after surgery, in which 3 patients in complex group accepted reoperation. Conclusions:Echocardiography can diagnose different types of SMR and associated malformations, evaluate surgical outcomes, and follow up for recurrence of SMR. Patients with simple SMR have better surgical results, but there is still a certain recurrence rate of stenosis.

Objective To analyze the midterm outcome of patients with congenital aortic stenosis undergoing percutaneous balloon aortic valvuloplasty (PBAV) by single echocardiographic guidance. Methods The clinical data of 12 patients with congenital aortic stenosis who underwent PBAV by single echocardiographic guidance at Fuwai Hospital from January 2016 to November 2017 were retrospectively analyzed. There were 7 males and 5 females with an average age of 18.27±15.30 years. The preoperative peak pressure gradient was 61.8–110.0 (80.30±24.50) mm Hg, and 50% of patients had aortic regurgitation. Results All patients successfully underwent PBAV. Aortic annulus diameter was 18.65±3.17 mm and balloon diameter was 17.62±3.77 mm, with balloon diameter to annulus diameter ratio of 0.92±0.07. The peak transaortic gradient was 16-51 (36.72±12.33) mm Hg immediately after procedure, which was significantly different from the preoperation (P=0.000). During the follow-up period, the peak transaortic gradient was 21-58 (37.06±13.52) mm Hg, and there was no significant difference between the follow-up and immediate postoperation (P=0.310). Immediately after procedure and during follow-up, 58% of patients had aortic regurgitation, which was not statistically different from the preoperation (P=0.682). Conclusion Systematic use of Doppler echocardiographic guidance for PBAV is feasible, and that it is associated with a high success rate and a very low complication rate.

To isolate corynoline from Corydalis bungeana Turcz.and study its anti-inflammatory mechanism via TLRs/NF-κB signal pathway.Corynoline was extracted by 80％ ethanol and purified by silicagel column chromatography.The structure and purity of corynoline was determined by UPLC,MS,1H NMR and 13C NMR.In the course of experiment,the cytotoxicity of corynoline was evaluated by MTT assay.And the inflammation model was established by RAW264.7 macrophages induced by lipopolysaccharide(LPS),which was intervened by coryno line.The expression levels of TLR4,TLR2 and nuclear transcription factor-κB(NF-κB) signaling pathways related proteinsin RAW264.7 macrophages were detected by Western blot.Furthermore,the expressionof NF-κB p65 mRNA and nuclear p65 were determined by the real-time fluorescence quantitative PCR(RT-qPCR) and Western blot.Results showed that 5-40 μmol/L corynoline reduced the expression level of TLR4 and TLR2,and inhibited the phosphorylation level of IκBα and the phosphorylation and nuclear translocation of p65 at gene and protein levelin a dose-dependent manner in LPS-induced RAW264.7 cells.This study indicated the protective effect of corynoline on LPS-induced RAW264.7 macrophages may be related with the inhibition of TLRs/NF-κB inflammatory signaling pathway.

Extract of Caragana sinica iv (100mg/kg, 200mg/kg ) significantly decreased the viscosity of wliole blood, plasma viscosity and whole blood reductive viscosity in rabbiLs. It also decreased fibrinogen cotent in plasma, and shortened platelet eletrophoresis time. In addition,extract of C. sinica significantly inhibited platelet adhesiveness.