ObjectiveTo compare the application value of two endoscopic ultrasound （EUS）-guided targeted vascular embolization techniques in secondary prevention of esophagogastric variceal bleeding （EGVB）， and to clarify the clinical advantages of targeted main trunk embolization. MethodsA retrospective analysis was performed for 59 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from April 2023 to July 2024 and received secondary prevention of gastroesophageal varices （GOV）-type EGVB， and according to the surgical procedure， they were divided into EUS-PCSS targeting the distal segment of the source vessel or perforating branch vessels （EUS-PCSS-D/P） group with 29 patients and EUS-PCSS targeting the source vascular trunk （EUS-PCSS-T） group with 30 patients. The two groups were observed in terms of rebleeding rate， variceal eradication efficiency， and the incidence rate of adverse events. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Mann-Whitney U test was used for subgroup analysis， and ordinal Logistic regression was used for multivariate analysis. ResultsThere were no significant differences in baseline data between the two groups （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly smaller diameter of punctured vessels （5.39±2.03 mm vs 7.00±2.21 mm， t=3.012， P=0.005）， a significantly lower treatment rate of supplementary endoscopic injection sclerotherapy （EIS） （40.00% vs 79.31%， χ²=7.521， P=0.006）， and a significantly lower amount of lauromacrogol used （16.08±7.25 mL vs 22.17±6.83 mL， t=2.518， P=0.015）， and there were no significant differences between the two groups in the amount of tissue adhesive used， the number of puncture sites， and treatment costs （all P>0.05）. There were no significant differences between the two groups in rates of GOV-related and all-cause gastrointestinal rebleeding （all P>0.05）. Compared with the EUS-PCSS-D/P group， the EUS-PCSS-T group had a significantly lower number of treatment sessions required for GOV eradication （2.00 ［1.25 — 2.00］ vs 3.00 ［2.00 — 4.00］， Z=3.872， P<0.001）， with a higher two-session eradication rate （50.00% vs 17.86%， χ²=7.102， P=0.008） and a lower eradication rate for three or more sessions （23.33% vs 71.43%， χ²=15.326， P<0.001）. The subgroup analysis showed that history of endoscopic treatment and supplementary EIS did not affect the number of treatment sessions required for GOV regression （all P>0.05）， and the ordinal Logistic regression analysis showed that treatment grouping was an independent influencing factor for the number of treatment sessions required for GOV regression （odds ratio=0.32， 95% confidence interval： 0.15 — 0.68， P=0.007）. There was no significant difference in the incidence rate of adverse events between the two groups （P>0.05）， and no ectopic embolism was observed in the EUS-PCSS-T group. ConclusionThe EUS-PCSS-T procedure can significantly improve the eradication efficiency of GOV and reduce the number of treatment sessions； its efficacy is not affected by history of endoscopic treatment or supplementary EIS therapy， and it has a favorable safety profile.

Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*

To summarize the postoperative nursing experience for a child with Uhl's anomaly undergoing complex heart surgery.Nursing key points include implementing goal-oriented liquid negative balance management to promote the recovery of cardiac function;carrying out pressure load management and closely monitoring the heart rate and rhythm to maintain the stability of the circulatory system;closely monitoring the central venous pressure in the upper chamber and paying attention to the changes of the pulmonary artery pressure in real time;adopting a refined integrated management to avoid an abnormal rise in the pulmonary artery pressure;withdrawing invasive mechanical ventilation as early as possible and carrying out the non-invasive ventilator deconditioning training in an orderly manner;the synergistic management of bleeding and anticoagulation;the adoption of various measures to actively prevent complications;the prevention and control of infections in an all-round and multi-angle manner;the formulation of individualized cardiac rehabilitation training and nutritional intervention programs.The child was transferred from the pediatric intensive care unit back to the pediatric ward on postoperative day 9,transferred back to the pediatric intensive care unit on postoperative day 11 for 13 d for right atrial thrombus,stabilized and transferred back to the pediatric ward,and discharged after 10 d for recovery.The prognosis showed good recovery after 1 month and 3 months.

OBJECTIVE To establish a liquid chromatography massspectrometry(LC-MS/MS)method for quantitatively determining the concentration of cepharanthine in rat plasma and tissue samples after intravenous injection of cepharanthine hydrochloride.METHODS ①The LC-MS/MS method was adopted.A Phenomenex C18(3.0 mm×50 mm,2.6 μm)column was employed with a mobile phase consisting of 0.05%formic acid-2 mmol·L-1 ammonium acetate-water solution and 0.1%formic acid-acetonitrile solution under gradient elution at a flow rate of 0.6 mL·min-1.The determination was performed using positive ion multiple reaction monitoring mode assays:cepharanthine(m/z:607.3→365.1)and buspirone(IS)(m/z:386.4→122.2).② Blood samples were collected from 6 SD rats at different time points following a single iv administration of cepharanthine to determine the concentration of the drug.The main pharmacokinetic parameters were calculated using a non-compartmental model.③72 SD rats were subjected to tissue distribution experiments after a single and multiple iv administra-tion of cepharanthine,and tissue samples were collected at six different time points(n=6)for the quanti-fication of drug concentrations.④ The whole blood plasma distribution ratio(Rb/p)of cepharanthine hydrochloride(7.5 mg·kg-1)in 3 SD rats was determined 2 h after iv administration.⑤The protein binding of cepharanthine to rat plasma and lung tissue homogenates was determined by equilibrium dialysis before the concentration of the free drug within the lungs was calculated.RESULTS ① An LC-MS/MS method for quantitatively determining cepharanthine in rat plasma and tissue homogenates was devel-oped,which demonstrated an excellent linear relationship(r2>0.999)within the concentration range of 2 to 1000 μg·L-1,with a lower limit of quantification at 2 μg·L-1.The obtained results met all the require-ments for accurate quantitative detection.②The main pharmacokinetic parameters of cepharanthine in rats following a single iv administration were as follows:C0=(686.91±238.43)μg·L-1,t1/2=(29.70±6.29)h,Vz=(62.70±7.93)L·kg-1,Vss=(62.55±11.28)L·kg-1,CL=(1.50±0.23)L·h-1·kg-1 and AUC(0-t)=(4.52±0.61)h·mg·L-1.③ Concentrations in tissues exceeded those in plasma after both a single and multiple iv administration,with the highest levels in the lung.The values of AUC(0-t)in lungs were(2 547.35±156.56)and(4 481.35±479.21)h·mg·L-1 after a single and multiple iv administration,respectively.④ The content of cepharanthine in blood cells was higher than that in plasma,and Rb/p was 3.5±0.8.⑤ After correction by the protein-binding rate,the minimum concentration of free drugs in the lungs(95.04 μg·L-1)exceeded the reported antiviral activity threshold against coronaviruses(EC50=60.67 μg·L-1).CONCLUSION An LC-MS/MS method has been established to rapidly and sensitively determine the concentration of cepharanthine in rat plasma and tissues.Following intravenous administration of ceph-aranthine hydrochloride,the pulmonary exposure level of the drug is significantly higher in plasma and other tissues,providing data for evaluating its in vivo pharmacological activities.

Objective To explore the expert consensus on perinatal care management of infants with congenital heart disease(hereinafter referred to as"Consensus")in order to promote the standardization of integrated nursing.Methods The literature was systematically searched and several discussions were organized within the group to compile the first draft of the Consensus.From January to March 2024,20 experts in the clinical nursing,nursing management,clinical medicine and other fields of congenital heart disease were solicited through 2 rounds of Delphi,and 8 experts were invited to conduct a validation to revise the items to form the final Consensus.Results The recovery rates of the 2 rounds of questionnaires were 100％;the experts'authority coefficient was 0.89;the Kendall's W were 0.172,0.211,with statistical significance(P＜0.05).The Consensus included 8 first-level subjects,namely prenatal examination and consultation,postpartum screening,standardized referral,preoperative nursing,intraoperative nursing,postoperative nursing,other disease screening,health education and discharge follow-up.Conclusion The Consensus is scientific and rigorous,and it can provide a reference basis for clinical nursing staff to carry out the care and management of newborns with congenital heart disease.

Objective:To construct three photosensitive fusion proteins between protein G C3 domain and Avitag for site-spe-cific biotinylation of goat IgG.Methods:DNA sequences of protein G C3 domain with amber codon mutation and C-terminal containing 1,2,3 Avitag were obtained by chemical synthesis,respectively,and sub-cloned into pTXB1 plasmid to construct three fusion pro-tein expression vectors.Three plasmids and pEVOL-pBpF plasmid were co-transformed into competent bacterium E.coli BL21,respec-tively.Target fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were prepared using genetic codon extension technology,and were purified by His Trap Chelating HP column,then biotinylated by Avitag/BirA system.Photo-conjugation efficiency,crosslink site and antigen-binding activity of photo-conjugates were investigated by SDS-PAGE,control experiment,and competitive ELISA.Results:Three expression vectors were successfully constructed,and three designed photoactivatable fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were successfully expressed with molecular weights consistent with their theoretical values.Heavy-chain conjugation efficiencies of biotinylated fusion protein with goat IgG were 85%with Fc-specific conjugation,and conjugates maintained its antigen-binding activity after photo-conjugation.Conclusion:CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 fusion proteins are successfully prepared,and mediates by those photosensitive fusion proteins,biotins molecules are conjugated to Fc fragment of goat IgG,results site-specific biotinylation of goat IgG.

Objective To investigate the risk factor for adverse events(AEs)after non-sedated esophagogastroduodenoscopy(EGD).Methods The data on clinical manifestations,adverse events after non-sedated EGD and common risk factors were collected and retrospectively analyzed with statistical methods in patients who underwent non-sedated EGD from May 2018 to June 2019.These patients were divided into AEs group and non-AEs group.Results Of 2 384 patients,57.67%(1 375/2 384)presented with nausea,12.79%(305/2 384)vomiting,and 5.79%(138/2 384)presented with pharyngalgia.Multivariate Logistic regression analysis was performed.Advanced age(≥65 years old)(OR=0.683,95%CI:0.506-0.921)was protective factors for nausea after non-sedated EGD.Hypertension(OR=1.361,95%CI:1.026-1.806),overweight(OR=1.399,95%CI:1.154-1.695),obesity(OR=2.594,95%CI:1.760-3.823)and inspection duration>15 min(OR=3.107,95%CI:2.296-4.206)were independent risk factors for nausea after non-sedated EGD.Advanced age(OR=0.393,95%CI:0.221-0.699)and imported equipment(OR=0.697,95%CI:0.546-0.890)were protective factors for vomiting after non-sedated EGD.Moreover,inspection duration>15 min(OR=1.641,95%CI:1.008-2.699)was independent risk factors for vomiting after non-sedated EGD.There was no difference in success rate of non-sedated EGD between two groups(P<0.05).Conclusion Hypertension,overweight and obesity were independent risk factors for nausea after non-sedated EGD.The advanced age and imported equipment were protective factors for vomiting after non-sedated EGD.In addition,inspection duration over 15 min is a risk factor for AEs such as nausea and vomiting after nonsedative EGD.Whether AEs occurred or not is non-related to success rate of non-sedated EGD.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Objective To screen natural small-molecule compounds with anti-Helicobacter pylori urease(HPU)activity based on traditional Chinese medicine active ingredients and to systematically investigate their inhibitory mechanisms against HPU,as well as their regulatory effects on cellular inflammation and oxidative stress following Helicobacter pylori(Hp)infection.Methods A multi-dimensional screening strategy was adopted.Firstly,virtual screening was performed on the traditional Chinese medicine monomer compound database based on the crystal structure of HPU,and the candidate molecules were selected in combination with bibliometric analysis.Subsequently,the modified Berthelot method was applied to verify urease inhibitory activity in vitro.Inhibition kinetics were analyzed with Lineweaver-Burk plots.The inhibitory sites were explored through sulfhydryl blocking agents and Ni2+competitive inhibitors,followed by molecular docking simulations with AutoDock Vina(version 1.2.3).A Hp-infected human gastric mucosal epithelial cells(GES-1)model was established.The compound's cytotoxicity was assessed with the CCK-8 assay and lactate dehydrogenase release assay.The mRNA expression levels of interleulain(IL)-6,IL-8,and IL-1β were quantified with quantitative real-time PCR(qRT-PCR).Intracellular reactive oxygen species(ROS)levels were measured with a DCFH-DA fluorescent probe.Results According to the screening results,the natural small-molecule compound rhodiosin(RHO)significantly inhibited HPU activity with a half-maximal inhibitory concentration(IC50)of(82.38±5.45)μmol/L.Enzyme kinetics analysis revealed that RHO acted as an anti-competitive inhibitor,showing an inhibition constant of(146.40±2.19)μmol/L;RHO-sulfhydryl/Ni2+-HPU interaction experiments confirmed that its target was located in the sulfhydryl group in the active center of HPU.Molecular docking simulations suggested that RHO is bound exactly to the Flap domain of the urease active pocket,with a binding energy of-8.678 kcal/mol.No significant cytotoxicity towards GES-1 cells was observed with RHO at 80 μmol/L in cellular experiments.Furthermore,RHO significantly down-regulates the mRNA overexpression of IL-6,IL-8,and IL-1β induced by Hp and reduces the production of ROS by 95%.Conclusion The monomer RHO of traditional Chinese medicine inhibits HPU through anti-competitive binding to the sulfhydryl site.It can effectively alleviate the inflammatory response and oxidative stress injury of GES-1 caused by Hp infection,providing a theoretical foundation for developing novel anti-Hp treatment strategies.