New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization(TACE)being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors(TKIs) and immune checkpoint inhibitors(ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

The water-soluble TF3 component from Eupolyphaga sinensis Walker promotes tibial fracture healing in rats by promoting osteoblast proliferation and angiogenesis

Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results: Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion: TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

胸外科术后重症患者下肢深静脉血栓形成及其凝血状态分析

背景与目的分析胸外科术后重症患者住重症加强护理病房(intensive care unit, ICU)期间的下肢深静脉血栓(deep venous thrombosis, DVT)发生率与凝血指标。方法回顾性分析2016年7月-2018年6月接受物理预防血栓的胸外科术后重症患者,将床旁下肢静脉超声、血常规、凝血四项、血栓弹力图等结果完善的病例纳入研究,对发生血栓人群的一般信息、病种、手术方式、凝血指标等进行分析。结果共纳入患者50例,年龄22岁-80岁,男34例,女16例。共有11例患者出现小腿深静脉血栓(22.0%),男性发生术后血栓的比例为29.4%(10/34),女性为6.3%(1/16)。恶性肿瘤的DVT发生率为23.5%(8/34),非恶性肿瘤的发生率为18.6%(3/16)。比较发生血栓和未发生血栓组的血小板计数、凝血四项、血栓弹力图等,除活化部分凝血活酶时间血栓组较无血栓组显著延长外,余无统计学差异。结论即便在充分物理预防的基础上,胸科术后重症患者下肢深静脉血栓仍为高发,且男性、恶性肿瘤患者多见;术后超声筛查有助于早期发现DVT。

Anatomy of Different Ages of Streblus asper Leaves and Their Drought Resistance

The leaf thickness, stratum corneum thickness, epidermis thickness, palisade tissue thickness and sponge tissue thickness of Streblus asper leaves at different ages were observed by using paraffin section technology and optical microscopic observation to explore the anatomic adaptive response mechanism to drought stress, also to provide a theoretical basis for S. asper introduction. The results showed that under drought stress, various parts of S. asper leaf anatomy showed some characteristics adapted to water environment. Leaf palisade tissue cells became shorter, increasing from 1-2 layers to 2-3 layers; sponge cells were arranged in neat and compact long column shape, and the upper and down epidermis were thickened. The upper and down epidermis produced more trichomes to resist stress. After rehydration, leaf porosity increased and trichomes had a corresponding reduction. The principal component analysis showed that the stratum corneum thickness, leaf thickness and palisade were available to describe the impact of stress and rehydration on different ages of S. asper leaf anatomy. Under drought stress, S. asper leaf stratum corneum thickness and leaf thickness increased and leaves returned to normal after rehydration. Middle and top leaves were better than basal leaves in response to drought stress sensitivity.

Measurement of Rural Inclusive Financial Development and Analysis of Spatial Effects on Anti-poverty

Based on two dimensions of supply and demand,we use six indicators to establish a rural inclusive financial development index and evaluate the development of China's rural inclusive finance. We use spatial panel data model to examine the relationship between financial inclusion and rural poverty. Results show that:( i) both the rural inclusive finance and rural residents' per capita consumption present spatial clustering feature and show significant spatial correlation;( ii) the development of rural inclusive finance has significant spatial effect on poverty alleviation along time and space dimensions. In this study,the paper puts forward policy recommendations on strengthening the rural financial resources flow and constructing diversified rural inclusive financial system.

Fecal metabolomics reveals the positive effect of ethanol extract of propolis on T2DM mice

A large number of studies have shown that propolis has positive effects in the treatment of type 2 diabetes mellitus(T2DM).However,there are have only been a few reports that are based on an ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS)analysis of the fecal metabolomics of ethanol extract of propolis(EEP)in the treatment of T2DM.The present investigation was designed to screen potential biomarkers of T2DM by the metabonomic method and to explain the possible anti-diabetes mechanism of EEP according to the changes in the biomarkers.The results showed that EEP improved the body weight(BW)of T2DM mice,lowered blood sugar levels,and significantly restored blood biochemical indicators related to T2DM,such as fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),aspartate transaminase(AST),and alanine aminotransferase(ALT).Liver pathology showed that EEP reversed liver damage caused by T2DM.Metabolomics data identified 27 potential biomarkers in fecal samples.EEP effectively regulated the dysfunction in the metabolic pathways of glycerophospholipids,sphingolipids,riboflavins,and sterol lipids caused by T2DM.In summary,our research results revealed positive effects of EEP in the treatment of T2DM and provided potential candidate markers for further research and in the clinical treatment of T2DM.

Anti-tumor activities of macromolecular fractions of fresh gecko vivo and their induction of Bel-7402 cell differentiation

Objective:To investigate the anti-tumor effect of macromolecular fractions of fresh gecko (M-AG) in vivo and their differentiation-inducing activity in Bel-7402 cells in vitro.Methods:An H22 hepatocarcinoma-bearing mouse model was used to evaluate the anti-tumor activity of M-AG samples.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to analyze cell viability.Cell morphology was observed by phase contrast microscopy.The quantity of the alpha-fetoprotein was detected by a radioimmunoassay.Chromatometry was used to assay the albumin quantity.Activities of alkaline phosphatase and γ-glutamyl trans-peptidase were measured by biochemical methods.Finally,western blotting was applied to assess proteins in the mitogen-activated protein kinase (MAPK) signaling pathway.Results:Macromolecular fractions of fresh gecko exerted a significant anti-tumor effect in mice.The inhibition rate of tumor growth was 63% in the moderate M-AG dose group.Cells treated with M-AG displayed a differentiated state.The treatment lowered alphafetoprotein secretion and significantly decreased the activities of γ-glutamyl trans-peptidase and alkaline phosphatase in Bel-7402 cells.In contrast,M-AG increased the amount of albumin in the cell culture medium.All biochemical indices demonstrated that M-AG induced Bel7402 cell differentiation.Western blotting showed no changes in the quantities of extracellular signal-regulated kinase (ERK) 1/2,p38MAPK,or c-Jun N-terminal protein kinase 1/2.However,M-AG significantly activated the phosphorylation of ERK1/2 in a dose-dependent manner.In addition,M-AG had no significant influence on the expression of nuclear factor-kappa B.Conclusion:Macromolecular fractions of fresh gecko has an anti-tumor activity in H22 hepatocarcinoma-bearing mice in vivo and inhibits Bel-7402 cell proliferation in vitro by inducing cell differentiation related to activation of ERK1/2.

新文科建设背景下以目标为导向的犯罪学课程教学改革研究

犯罪学是公安类专业的必修课,对警察职业综合能力培养起着重要奠基作用。当前犯罪学课程教学存在诸多问题,与新文科建设要求有着相当差距。为了贯彻落实新文科建设要求,犯罪学课程教学首先必须重新厘定课程目标。以课程目标分类理论和新文科建设要求为依据,犯罪学课程应兼顾认知、技能、情感价值观等三类课程目标。新文科建设背景下,以课程目标为导向,犯罪学课程教学改革应当着手于:科学规划和设计课程教学内容,优化和创新教学活动过程,完善和健全教学评价体系。

新文科建设背景下卓越警务人才培养基本问题研究

新文科建设为高校人才培养工作提供了理论指引和行动指南,它要求高校培养具有家国情怀和志存高远的社会主义事业建设者和接班人,要求高校以发展新兴、交叉学科为契机优化调整专业,培养具有新知识、新方法、新思维的复合型人才。就警察类专业而言,新文科建设要求其以卓越警务人才为培养目标,从思想、知识、能力、身心素质等方面赋予人才培养规格新的内涵。为了培养新时代需要的卓越警务人才,高校须促进学科交叉与融合,完善警察类专业课程体系;推动思政课程教学和专业课程思政教学同时发力,锻造忠诚警魂;积极优化课堂教学设计,促进学生警察职业综合能力提升;强化实践教学环节,提高学生的实践实战能力。

Research on microstructural evolution and dynamic recrystailization behavior of JB800 bainitic steel by FEM

Single pass compression tests were conducted on Gleeblel500 thermal simulator. The effect of different deformation parameters on the grain size of dynamically recrystallized austenite was analyzed. A mathematical model of dynamic recrystallization and a material database of JB800 steel, whose tensile strength is above 800 MPa, were set up. A subprogram was compiled using Fortran language and called by Marc finite element software. A thermal coupled elastoplastic finite element model was established to simulate the compression process. The grain size of recrystallized austenite obtained by different recrystallization models was simulated. The results show that the optimized dynamic recrystallization model of JB800 bainitic steel has a higher precision and yields good agreement with metallographic observations.

Effects of heat on the biological activity of wild Cordyceps sinensis

Background:Current methods of extending the storage time of wild Cordyceps sinensis adversely affect the nutritive and medicinal value of the product.Thus,this study was designed to investigate the effects of heat treatment,a relatively safe storage extension method,on the biological activity of wild C.sinensis.Methods:Samples were heated to 60,80,or 100℃ for 15,30,or 60 minutes.SOD activity in wild C.sinensis before and after heating was assayed using a standard colorimetric assay.Deoxyribonuclease (DNase) activity was measured using the plasmid-nicking assay.Cordycepin content was analyzed using HPLC.Polysaccharide content was measured using the phenol sulfuric method.The Student's t-test was used for comparison.Results:After heating at 60,80,100℃ for 15,30,60 minutes,respectively,no significant reduction in DNase activity or polysaccharide dissolution was noted (P >.05).Interestingly,heating at 80℃ for 30 minutes led to a significant increase in the SOD activity of C.sinensis (P <.05).In addition,heating at 60℃ for 60 minutes or at 80℃ for 15 minutes significantly increased cordycepin dissolution (P <.05).Other heat treatments had no significant effects on SOD activity or cordycepin dissolution (P >.05).Conclusions:These results suggested that heat treatment does not adversely affect SOD or DNase activity,polysaccharide content,or cordycepin dissolution.Thus,heat treatment might be a safe processing method to extend the storage time of wild C.sinensis without compromising biological activity.

Biotransformation of 6-deoxypseudoanisatin by Synechocystis sp. PCC6803

Objective:To explore the ability of Synechocystis sp.PCC6803 in transforming 6-deoxypseudoanisatin.Methods:The experiment was performed by incubating 6-deoxypseudoanisatin with the freshwater cyanobacterium Synechocystis sp.PCC6803 under continuous white light at 30C for 5 days.The crude converted product was detected using thin-layer chromatography(TLC)and further analyzed using high-performance liquid chromatography(HPLC)as well as HPLC with electron spray ionization mass spectrometry(HPLC-ESI-MS).Results:TLC results showed that 6-deoxypseudoanisatin was converted into a less polar product.HPLC and MS data indicated that the retention time of the converted product increased in comparison with the standard of 6-deoxypseudoanisatin.Conclusion:Thus,the study appears to demonstrate that Synechocystis sp.PCC6803 can transform 6-deoxypseudoanisatin.The polarity of the converted product is less than that of 6-deoxypseudoanisatin.

A new species in the genus Indoquedius Blackwelder(Coleoptera:Staphylinidae)from Yunnan,China

Indoquedius lii sp.nov.is described from Yunnan,China.The number of Indoquedius species has thus increased to 39.Color images of the habitus,sternites,tergite and aedeagus of this new species are included.A key to species in the genus Indoquedius of Yunnan is provided.

Optimal Path Finding Method Study Based on Stochastic Travel Time

Finding optimal path in a given network is an important content of intelligent transportation information service. Static shortest path has been studied widely and many efficient searching methods have been developed, for example Dijkstra’s algorithm, Floyd-Warshall, Bellman-Ford, A* et al. However, practical travel time is not a constant value but a stochastic value. How to take full use of the stochastic character to find the shortest path is a significant problem. In this paper, GPS floating car is used to detect road section’s travel time. The probability distribution of travel time is estimated according to Bayes estimation method. The combined probability distribution of a feasible route is calculated according to probability operation. The objective function is to find the route that has the biggest probability to arrive for desired time thresholds. Improved Genetic Algorithm is used to calculate the optimal path. The efficiency of the proposed method is illustrated with a practical example.

Erratum to: Tannic acid coated single-wall carbon nanotube membranes for the recovery of Au from trace-level solutions

Erratum to Nano Research,2023,16(8):11350–11357 https://doi.org/10.1007/s12274-023-5803-y The article"Tannic acid coated single-wall carbon nanotube membranes for the recovery of Au from trace-level solutions",written by Chunmei Wang et al.,was erroneously originally published electronically on the publisher’s internet portal(currently SpringerLink)on 27 June 2023 with Fig.3(a).In Fig.3(a),the rejection of MWCNT is 38.9%instead of 98.3%.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its sub-variants.This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies.Here,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its sub-variants.Cryo-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S protein.The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex.Furthermore,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus particles.Compared to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro.The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.