Objective:To evaluate the clinical efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV) via antegrade venous-arterial loop in neonates with critical pulmonary stenosis with intact ventricular septum (CPS-IVS).Methods:A retrospective case review was conducted. Fifteen neonates with CPS-IVS who underwent PBPV via antegrade venous-arterial loop at the Women and Children′s Hospital, Qingdao University between September 2020 and September 2023 were included. Pre-and post-operative right ventricular functional parameters, surgical complications, and follow-up outcomes were analyzed. Paired-sample t-test was used to compare changes in right ventricular systolic pressure (RVSP), percutaneous oxygen saturation (SpO 2), and echocardiographic findings pre-and post-operatively, as well as during the follow-up period. Results:Among the 15 neonates (9 males and 6 females) with CPS-IVS, the surgical age was (3.6±0.5) d. All neonates underwent successful PBPV via antegrade venous-arterial loop under general anesthesia. The immediate post-operative trans-pulmonary valve pressure gradient was (35±6) mmHg (1 mmHg=0.133 kPa), with a significant reduction in RVSP from (96±16) mmHg to (59±14) mmHg ( t=6.70, P<0.001). SpO 2 (with an inspired oxygen concentration of 0.48) increased from 0.86±0.07 pre-operatively to 0.97±0.03 post-operatively ( t=4.81, P<0.001). One month postoperatively, SpO 2 (without oxygen supplementation) normalized in all patients, with a statistically significant difference compared to pre-operative values ( t=0.16, P<0.001). Immediately postoperative, mild to moderate diastolic pulmonary valve regurgitation was observed in 8 patients, with no cases of severe regurgitation. Additionally, the severity of tricuspid valve regurgitation decreased from severe to mild-to-moderate in 6 patients. Three months postoperatively, one patient underwent a second PBPV due to an increased trans-pulmonary valve pressure gradient of 74 mmHg, which decreased to 27 mmHg immediately after the procedure, with subsequent good recovery. Over a one-year follow-up period, all 15 patients demonstrated improvements in right ventricular indices. The Z-score of the tricuspid valve annulus significantly improved from -1.9±0.8 pre-operatively to -0.4±0.1 post-operatively ( t=6.88, P<0.001). At the last follow-up, mild to moderate pulmonary valve regurgitation was observed in 3 patients, and mild tricuspid regurgitation in 2 patients, with no cases of moderate or severe regurgitation. Conclusion:Intervention via antegrade venous-arterial loop for the treatment of CPS-IVS in neonates is safe and effective.

Objective:To establish HPLC fingerprint and methods for determining the contents of four iridoid glycosides of Gentiana rigescens; To evaluate the quality of Gentiana rigescens from different origins; To improve the quality control level of Gentiana rigescens medicinal materials.Methods:Using 15 batches of Gentiana rigescens from the main production areas and authentic production areas as raw materials, the common mode of HPLC fingerprints of Gentiana rigescens was established, and the chemical components of the common peaks were identified. Referring to the common mode of fingerprints, similarity analysis was conducted on the fingerprints of Gentiana rigescens from different origins. Using chemometric methods, cluster analysis (HCA), principal component analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed on 15 batches of Gentiana rigescens, with the common peak area of fingerprint as the variable. The contents of four types of iridoid glycosides in Gentiana rigescens were determined. Combined with the fingerprints and the content results of four types of iridoid glycosides, the quality of Gentiana rigescens from different origins was evaluated.Results:The fingerprints of Gentiana rigescens contained 9 common peaks, with 4 identified iridoid glycosides. The similarity of the fingerprints of 15 batches of Gentiana rigescens ranged from 0.962 to 0.999. HCA and PCA divided the 15 batches of Gentiana rigescens into two categories. OPLS-DA analyzed 3 significantly different components, namely gentiopicroside, peak 7, and loganic acid. The content determination results showed that the average contents of loganic acid, swertiamarin, and gentiopicroside in Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province were the highest, and the total amount of four iridoid glycosides was also significantly higher than that from other regions, indicating that the overall quality of Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province was relatively good.Conclusion:This method is simple, fast, accurate, and can provide reference for improving the quality standards of Gentiana rigescens.

Objective:To identify the components of Prunus mume f. viridicalyx based on ultra performance liquid chromatography-QE-Orbitrap mass spectrometry (UPLC-QE-Orbitrap-MS); To predict and analyze its substances and mechanisms to exert anti-depression effects combined with network pharmacology.Methods:UPLC-QE Orbitrap MS technology was used to analyze the chemical components of Prunus mume f. viridicalyx. Based on ChemSpider, mzCloud online platform, orbitrap TCM library and existing literature research, the secondary mass spectra of target compounds were compared and confirmed to identify the chemical composition of Prunus mume f. viridicalyx. The active components of the Prunus mume f. viridicalyx were screened. The Swiss Target Prediction database was used to predict targets with high correlation to active components in Prunus mume f. viridicalyx, and obtaining depression related disease targets from GeneCards and DisGeNET databases. The intersection targets of constituents and diseases were obtained using Venny platform. Protein-protein interaction network (PPI) was constructed by using String database, and the core targets were screened. Gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of potential core targets were performed by using David database, and "active component-core target-signal pathway" network was constructed. PyMOL software was used to perform molecular docking between active components and key targets.Results:A total of 54 components, including organic acids, flavonoids and their glycosides, alkaloid, amino acids and other compounds were identified from Prunus mume f. viridicalyx. A total of 22 active components were screened and 92 active components and disease intersection targets were identified. A total of 13 core targets were screened through PPI network, including tumor necrosis factor, albumin, amyloid beta-protein precursor, AKT serine/threonine kinase 1 and so on. Enrichment analysis showed that Prunus mume f. viridicalyx mainly participated in transcription from RNA polymerase Ⅱ promoter, gene expression, protein binding and other functions, and presented the effects of anti-depression through MAPK, Toll-like receptor signaling pathway and other pathways. 12 key targets and 7 key active components were further obtained through the analysis of the "active component-core target-signal pathway" network, three of them were confirmed as kaempferol, quercetin, and isorhamnetin by reference substance. Molecular docking showed that 3 compounds could bind to the target proteins of depression well.Conclusion:Prunus mume f. viridicalyx exerts antidepressant effects through multiple components, targets, and pathways, mainly through the MAPK signaling pathway.

Objective:To evaluate the clinical efficacy of percutaneous balloon pulmonary valvuloplasty (PBPV) via antegrade venous-arterial loop in neonates with critical pulmonary stenosis with intact ventricular septum (CPS-IVS).Methods:A retrospective case review was conducted. Fifteen neonates with CPS-IVS who underwent PBPV via antegrade venous-arterial loop at the Women and Children′s Hospital, Qingdao University between September 2020 and September 2023 were included. Pre-and post-operative right ventricular functional parameters, surgical complications, and follow-up outcomes were analyzed. Paired-sample t-test was used to compare changes in right ventricular systolic pressure (RVSP), percutaneous oxygen saturation (SpO 2), and echocardiographic findings pre-and post-operatively, as well as during the follow-up period. Results:Among the 15 neonates (9 males and 6 females) with CPS-IVS, the surgical age was (3.6±0.5) d. All neonates underwent successful PBPV via antegrade venous-arterial loop under general anesthesia. The immediate post-operative trans-pulmonary valve pressure gradient was (35±6) mmHg (1 mmHg=0.133 kPa), with a significant reduction in RVSP from (96±16) mmHg to (59±14) mmHg ( t=6.70, P<0.001). SpO 2 (with an inspired oxygen concentration of 0.48) increased from 0.86±0.07 pre-operatively to 0.97±0.03 post-operatively ( t=4.81, P<0.001). One month postoperatively, SpO 2 (without oxygen supplementation) normalized in all patients, with a statistically significant difference compared to pre-operative values ( t=0.16, P<0.001). Immediately postoperative, mild to moderate diastolic pulmonary valve regurgitation was observed in 8 patients, with no cases of severe regurgitation. Additionally, the severity of tricuspid valve regurgitation decreased from severe to mild-to-moderate in 6 patients. Three months postoperatively, one patient underwent a second PBPV due to an increased trans-pulmonary valve pressure gradient of 74 mmHg, which decreased to 27 mmHg immediately after the procedure, with subsequent good recovery. Over a one-year follow-up period, all 15 patients demonstrated improvements in right ventricular indices. The Z-score of the tricuspid valve annulus significantly improved from -1.9±0.8 pre-operatively to -0.4±0.1 post-operatively ( t=6.88, P<0.001). At the last follow-up, mild to moderate pulmonary valve regurgitation was observed in 3 patients, and mild tricuspid regurgitation in 2 patients, with no cases of moderate or severe regurgitation. Conclusion:Intervention via antegrade venous-arterial loop for the treatment of CPS-IVS in neonates is safe and effective.

Objective To establish the ultra-high performance liquid chromatography(UPLC)chromatographic fingerprint of Notopterygii Rhizoma et Radix;To determine the contents of ferulic acid,nodakenin,ammijin,notopterol,isoimperatorin and volatile oil of Notopterygii Rhizoma et Radix from different producing areas;To provide reference for quality evaluation of Notopterygii Rhizoma et Radix.Methods Waters BEH C18 chromatographic column(2.1 mm×150 mm,1.7 μm)was used,with mobile phase acetonitrile-0.02%formic acid aqueous solution gradient elution,flow rate 0.25 mL/min,column temperature 25℃,detection wavelength 330 nm,injection volume 2 μL.UPLC fingerprints of 25 batches of Notopterygii Rhizoma et Radix were established,and the similarity analysis and chemometrics analysis were carried out.The contents of ferulic acid,nodakenin,ammijin,notopterol and isoimperatorin were determined simultaneously,and the contents of volatile oil was determined by steam distillation method.Results Totally 23 common fingerprint peaks were calibrated,11 known components were identified.According to the results of the cluster analysis and principal component analysis,25 batches of Notopterygii Rhizoma et Radix samples were divided into 3 categories,and the 6 potential differential components were screened out by orthogonal partial least squares-discriminant analysis(OPLS-DA).The results showed that the contents of notopterol and volatile oil from Sichuan Province were higher than those from Gansu Province and Qinghai Province.Conclusion The method established in the study is accurate and reliable,which can provide scientific basis and reference for the quality evaluation and control of Notopterygii Rhizoma et Radix.

Organoid technology for primary liver cancer presents a novel in vitro model that faithfully reproduces the tissue architecture and genetic characteristics of liver cancer, serving as a platform for drug efficacy testing and disease mechanism exploration. Despite hurdles such as modest cultivation success rates and the challenge of fully mimicking the tumor microenvironment, the progression of liver cancer organoid technology holds the potential for advancing personalized medicine and tailored therapies, positioning it as a critical instrument in the investigation of liver cancer treatment strategies. This review delineates the techniques for construction methods of liver cancer organoids, their applications, and the existing constraints.

Objective:To establish ultra performance liquid chromatography (UPLC) characteristic chromatogram of Pulsatilla chinensis; To provide reference for the origin identification and quality control of Pulsatilla chinensis. Methods:UPLC Method was adopted. The determination was performed on a column of Agilent SB C18 (2.1 mm×100 mm, 1.8 μm) . The mobile phase was acetonitrile-methanol (2:1) -0.1% phosphoric acid solution by fradient elution at a flow rate of 0.30ml/min. The column temperature was 30 ℃. The detection wavelength was 215 nm. The injection volume was 2 μl. The common counterfeit products and medicinal herbs of Pulsatilla chinensis from different areas were evaluated by comparison of characteristic chromatogram, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Results:There were 9 characteristic peaks in the characteristic chromatogram of Pulsatilla chinensis, and 8 common peaks were identified by high resolution mass spectrometry and comparison of reference materials. Through PCA analysis, it was possible to clearly distinguish the medicinal herbs of Pulsatilla chinensis from different areas. Combined with OPLS-DA analysis, it was found that peak 2, peak 3, peak 6 were the main markers of Pulsatilla chinensis from different producing areas. Conclusion:The established method has good specificity, repeatability and durability, and it can effectively distinguish the common counterfeits of Pulsatilla chinensis, and provide the basis of quality control and selection of origin for Pulsatilla chinensis.

Objective:To establish the ultra high performance liquid chromatography (UPLC) fingerprints of Mume flos at different flowering stages; To provide reference for the quality research of Mume flos.Methods:The fingerprints of Mume flos were established by UPLC method, and the common peaks were identified by high performance liquid chromatography high resolution mass spectrometry (LC-MS). Chemometrics analysis was carried out with the fingerprints' common peak area of plum blossom at different flowering stages as a variable. Semiquantitative analysis of changes in flavonoids and phenolic acids in Mume flos at different flowering stages was conduct using peak area calculation method.Results:Totally 31 common peaks were identified in the fingerprints of plum blossom medicinal materials at different flowering stages and 9 components were identified. Clustering analysis (HCA) and principal component analysis (PCA) both classified plum blossom medicinal herbs at different flowering stages into three categories. Among them, there were significant differences between the groups at the bud stage, blooming period, and final flowering period, while the differences between the groups at blooming period and final flowering period were relatively small. The orthogonal partial least squares discriminant analysis (OPLS-DA) screened 16 different components with VIP>1.0. The contents of phenolic acids in different flowering stages were as follows: bud stage>blooming period>final flowering period, while the contents of flavonoids were as follows: blooming period>final flowering period>bud stage.Conclusions:This method is simple and reliable, and can provide reference for the quality evaluation of plum blossom medicinal materials at different flowering stages.

Objective:To study the effects of different single cell phenotypes on the prognosis of patients with intrahepatic cholangiocarcinoma by using spatial analysis, providing clues for obtaining potential immunotherapeutic targets.Methods:This study was a retrospective cohort study. A total of 41 intrahepatic cholangiocarcinoma (ICC) patients who underwent surgery in Beijing Youan Hospital Affiliated to Capital Medical University from February 2013 to June 2019 were enrolled. According to the 5-year survival situation, the patients were divided into survival group ( n=10) and death group ( n=31). A metal label-based tissue imaging mass panel containing 36 related markers was designed and constructed for staining different components in tumor samples. Through the analysis of the type and quantity of different metacluster and spatial location information and combined with the clinical outcomes of patients with information, certain metaclusters were found related to the prognosis of patients. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), paired t-test was used for comparison between groups. Measurement data with skewed distribution were expressed as median, and rank sum test was used for comparison between groups. The chi-square test was used to compare the counting data between groups. Results:36 biomarkers of 41 ICC patients were located and quantified to generate 1 476 single-cell resolution histological images. The expression information of various markers was analyzed by t-distributed Stochastic Neighbor Embedding (tSNE), and subgroups annotations (1-29) were added. It revealed that the density of metacluster 7(CD8 + T cells) was lower in survival group. The density of metacluster 16(Bcl-2 + CK7 + cancer cells) within tumors, as well as the density of metacluster 3(Vista + GB + CD11b + neutrophils) within stroma were higher in death group. Conclusion:The density of metacluster 7(Activated CD8 + T cells), metacluster 16(Bcl-2 + CK7 + tumor cells) and a novel neutrophil metacluster 3(Vista + GB + CD11b + neutrophils) correlated with ICC patients prognosis.

Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.