Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To explore the effects of different fractionation doses,fractionation methods,and other related parameters on the peripheral blood lymphocyte count of patients with liver cancer receiving CyberKnife radiotherapy.Methods The clinical data of 90 patients with liver cancer receiving CyberKnife radiotherapy in our hospital were retrospectively analyzed.The peripheral blood lymphocyte counts of patients 1 week before CyberKnife radiotherapy and 1 week,1 month and 3 months after treatment were determined.The effects of different prescribed doses,fractionation doses and numbers of fractionations on the peripheral blood lymphocyte count were analyzed.Results The peripheral blood lymphocyte counts of patients with different prescribed doses,fractionation doses and fractionation methods after CyberKnife treatment decreased to varying degrees compared with those 1 week before treatment(P<0.05).The peripheral blood lymphocyte counts of patients in the groups with≤5 fractionations and fractionation dose>7 Gy were significantly higher than those of patients in the groups with>5 fractionations and the fractionation dose≤7 Gy,respectively(P<0.05).There was no significant difference in peripheral blood lymphocyte counts between patients with different prescribed doses before and after CyberKnife treatment(P>0.05).Conclusion CyberKnife in the treatment of liver cancer with≤5 ractionations and a fractionation dose of>7 Gy is more beneficial to alleviate the decrease of lymphocyte count caused by Cyberknife treatment.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Objective To design a portable intelligent cleaner for medical lumen instruments to enhance cleaning efficiency.Methods The portable intelligent cleaner had a box-body shape and a shell made of 304 stainless steel,which was composed of a circuit control board,a micro pump,lithium batteries,a charging interface,a rinse tube and connectors.The circuit control board used a STM32G030C8T6 integraged circuit,which was equipped with a countdown digital tube to display the time left for cleaning;the micro pump and lithium batteries were placed at the inner wall of the box bottom,the charging interface and water inlet/outlet inteface were put on the outside of the front wall of the box bottom,the water inlet/outlet interface was connected with a silicon rinse tube linked to an adapter at its distal end,and the adapters with different calibers were compatible with sizes of medical lumen instruments.Totally 9 672 pieces of lumen instruments received by some hospital's disinfection supply center from May to October 2021 were divided into 2 groups with the convenience sampling method,with 4 836 pieces in each group.The odd-numbered instruments were enrolled into a control group and cleaned with an ultrasonic cleaner and a lumen brush,and the even-numbered instruments were included into an experimental group and cleaned conventionally after pretreatment by the intelligent cleaner.The two groups were compared in terms of eaning efficiency and satisfaction.Results Testing by visual inspection,magnifying glass with light source and white stripe method showed that the experimental group behaved better than the control group in the cleaning qualification rate,whose satisfaction rate(100％)was also higher than that of the control group(86.53％),with all the differences being statistically significant(P＜0.05).Conclusion The portable cleaner with easy operation enhances the cleaning quality and efficiency for medical lumen instruments.[Chinese Medical Equipment Journal,2024,45(10):114-117]

Objective To conduct bibliometric visualization analyses of the literature domestic and overseas on active surveillance of post-marketing safety of drugs,aiming to display the current status and trend of hotspots in this field and to provide references for future research and the improvement of the Chinese management system of active surveillance.Methods The English and Chinese literature on active surveillance of post-marketing safety of drugs were searched in Web of Science and CNKI respectively and imported into CiteSpace 6.3.R2 software for the analysis of the number of publications,authors,institutions,and national cooperative networks,and the analysis of keyword co-occurrence,clustering and emergence.Results 415 Chinese and 676 English literature were included,with an overall increasing trend in annual publication volume.The author collaboration network of Chinese literature was smaller than that of English literature,and the partnership network was sparse,with no strong centralized institution.Domestic drug regulatory agencies played an important role in the field,while drug companies'monitoring research on their own products was still relatively scarce.The research topic covered active surveillance systems,technical method research,and drug safety active surveillance practice research for specific drugs and diseases.Conclusion Countries worldwide have widely considered active surveillance of post-marketing drug safety.The heat of research activities in China has shown a significant growth trend.However,there is still a significant gap compared with the international frontiers.Further cooperation needs to be strengthened to promote the improvement of the active surveillance management system in China.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

The post-translational modification of proteins is a key mechanism that imparts physiological functions to proteins,among which reversible phosphorylation modifications play a pivotal role in many biological processes.Aberrant changes in phosphorylation are often closely associated with various major disease processes.In recent years,with the aid of proteomic technologies and methods,high-throughput,high-precision qualitative and quantitative approaches for phosphorylated proteins have rapidly advanced.This article reviews the research progress of phosphorylated protein quantification and chemical proteomics analysis methods based on the"bottom-up"strategy,including phosphopeptide enrichment methods,mass spectrometry fragmentation methods,quantification analysis methods and phosphorylation site stoichiometry,and discusses the development trend of quantification and stoichiometric analysis methods for phosphorylated proteins.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

Objective To explore the clinical manifestations,endoscopic findings,histopathological changes,treatment,and prognosis of eosinophilic gastrointestinal disease(EGID)in children,with the aim of enhancing awareness among pediatricians about this condition.Methods Data of 267 children with EGID were prospectively collected from January 2019 to July 2022 at Jiangxi Children's Hospital,Hunan Children's Hospital,and Henan Children's Hospital.The age of onset,symptoms,physical signs,laboratory examination results,endoscopic findings,histopathological changes,and treatment outcomes were observed.Results Among the 267 children with EGID,the majority had mild(164 cases,61.4% )or moderate(96 cases,35.6% )clinical severity.The disease occurred at any age,with a higher prevalence observed in school-age children(178 cases).The main symptoms in infants were vomiting and hematemesis,while in toddlers,vomiting and bloody stools were prominent.Abdominal pain and vomiting were the primary symptoms in preschool and school-age children.Nearly half(49.4% )of the affected children showed elevated platelet counts on hematological examination,but there was no significant difference in platelet counts among children with mild,moderate,and severe EGID(P>0.05).Endoscopic findings in EGID children did not reveal significant specificity,and histopathological examination showed no specific structural damage.Among them,85.0% (227 cases)received acid suppression therapy,34.5% (92 cases)practiced dietary avoidance,20.9% (56 cases)received anti-allergic medication,and a small proportion(24 cases,9.0% )were treated with prednisone.Clinical symptoms were relieved in all patients after treatment,but three cases with peptic ulcers experienced recurrence after drug discontinuation.Conclusions Mild and moderate EGID are more common in children,with no specific endoscopic findings.Dietary avoidance,acid suppression therapy,and anti-allergic medication are the main treatment methods.The prognosis of EGID is generally favorable in children.[Chinese Journal of Contemporary Pediatrics,2024,26(2):139-144]