Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Objective:To verify the feasibility of using Elekta accelerated go live (AGL) standard process for the acceptance of multiple accelerators.Methods:The beams of three accelerators were adjusted by PTW Beamscan three-dimensional water tank to reach the AGL standard. Dose verification was performed for three accelerators that met AGL standards. A simple field test example from Cancer Hospital Chinese Academy of Medical Sciences was used to compare the MapCheck 3 surface dose measurement results with the surface dose calculated by the same accelerator model. Images of 10 patients including head and neck, esophagus, breast, lung and rectum were randomly selected. volumetric-modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) treatment techniques were used for planning design, and the measured dose of ArcCheck was compared with the planned dose calculated by the same accelerator model. One-way ANOVA was used to statistically analyze the passing rates of two-dimensional and three-dimensional dose verification.Results:The 6 MV X-ray percentage depth dose at 10 cm underwater (PDD 10) of three accelerators was 67.45%, 67.36%, 67.47%, and the maximum deviation between the three accelerators was 0.11%. The 6 MV flattenting filter free (FFF) mode X-ray PDD 10 was 67.33%, 67.20%, 67.20%, and the maximum deviation between the three accelerators was 0.13%. All required discrete point doses on each energy 30 cm×30 cm Profile spindle of the three accelerator X-rays deviated less than ±1% from the standard data. Absolute γ analysis was performed on the results of MapCheck 3 two-dimensional dose matrix validation. Under the 10% threshold of 2 mm/3% standard, the average passing rate of the test cases in Cancer Hospital Chinese Academy of Medical Sciences was above 99%, and the difference was not statistically significant ( P>0.05). Absolute γ analysis was performed on the ArcCheck verification results. Under the 10% threshold, the pass rate of 2 mm/3% was all above 95%, the maximum average passing rate of the three accelerators with different energy and different treatment techniques was 0.28% (6 MV, VMAT), 0.19%(6 MV FFF, VMAT), 0.56% (6 MV, IMRT) and 0.05% (6 MV FFF, IMRT), and the difference was not statistically significant ( P>0.05). Conclusion:Compared with traditional accelerator acceptance process, the acceptance time of each accelerator is shortened by 4-6 weeks by using the AGL standard process, and the radiotherapy plan of patients can be interchangeably executed among different accelerators.

Objective:To obtain hepatitis B virus capsid-like particles (CLPs) displaying B-cell linear epitopes of SARS-CoV-2 spike protein and evaluate their immunogenicity.Methods:Four recombinant plasmids expressing fusion proteins (M1-HBc, S1-57-HBc, S14P5-HBc and S21P2-HBc) were constructed by separately replacing codon of alanine at position 80 of hepatitis B virus core protein (HBc) with four genes coding for four B-cell linear epitopes (M1, S1-57, S14P5 and S21P2). These four recombinant proteins were expressed in E. coli BL21 Star (DE3) strains. The expression products were identified using SDS-PAGE, Western blot and native agarose gel electrophoresis (NAGE). CLPs were purified by sucrose density gradient ultracentrifugation, verified for antigenicity by Western blot and used to immunize BALB/c mice. Serum antibody titers were detected by ELISA. Results:The recombinant fusion proteins M1-HBc and S1-57-HBc self-assembled into M1-CLP and S1-57-CLP. The titer of antibody against S1-57 polypeptide in S1-57-CLP-immunized mouse serum approached 1∶1 000 000.Conclusions:Hepatitis B virus CLPs displaying SARS-CoV-2 M1 or S1-57 linear epitopes are successfully expressed in a prokaryotic system and purified. S1-57-CLP has good immunogenicity. This study provides a new idea for the development of novel diagnostic reagents and vaccines for SARS-CoV-2.

Clarifying the applicability （indications or contraindications） of traditional Chinese medicine （TCM） dietary regimens to different syndromes is a guarantee for the rational application and safety of TCM dietary therapy. By considering evidence from ancient literature， modern research and experts' experience， the Grading System for Syndrome Suitability of Dietary Therapy in TCM （GRADE-SSD） has been constructed. According to the currently available highest-quality evidence， GRADE-SSD classified the applicability of TCM dietary therapy to various TCM syndromes into 2 categories and 4 grades： "definitely" applicable/contradicted （Grade A）， "very likely" applicable/contradicted （Grade B）， "possibly" applicable/contradicted （Grade C）， and insufficient evidence to determine （Grade D）. When applying， first， systematically search the currently available ancient books and clinical research evidence. For different types of evidence （ancient TCM books， randomized controlled trials， observational studies， and meta-analyses）， use the prescribed tools to evaluate the quality of the evidence， and then determine the applicability level of TCM syndromes of dietary therapy based on the principle of "taking the highest" quality. If there is a lack of direct evidence， GRADE-SSD supports a downgraded evaluation based on indirect evidence of "similar prescriptions". When there is a lack of ancient books and clinical research， the GRADE-SSD plan can evaluate the quality of evidence from peer consensus or expert opinions for the applicability level of TCM syndromes of dietary therapy. Based on the requirements for the safety of TCM dietary therapy， when there is both "applicable" and "contradicted" evidence， it should be considered as "contradicted" evidence. GRADE-SSD also provides an evidence certainty update plan based on new evidence in the future. The evaluation results of GRADE-SSD can provide a basis for setting inclusion/exclusion criteria in clinical trials of TCM dietary therapy and stating the applicability of each syndrome in the labels of dietary therapy products.

Objective　To timely understand the current status and distribution of nail snails (Oncomelania hupensis) in Tongjiang River channels in Zhenjiang City, providing a scientific basis for achieving the goal of eliminating schistosomiasis. Methods　From 2019 to 2023, nine Tongjiang River channels on the south bank of the Yangtze River under the jurisdiction of Zhenjiang City were selected as the monitoring area. Snail monitoring was carried out onshore and beach nail snails floats in the Tongjiang River channels, nail snails on attachments in hardened areas, snails induced by straw curtains, and snails carried by boats and domestic animals. Results　The monitoring results of shoreline snail from 2019 to 2023 showed that the snail situation in the Tongjiang River channel and its outer river bank remained relatively stable from 2019 to 2020; however, in 2021, under the influence of the Yangtze River flooding disaster in 2020, the area of snails increased significantly. In 2021, the area with snails in the Tongjiang River channel and the outer river bank increased by 45.70% (11.95/26.15) and 100.00% (20.00/20.00) compared to 2020; the average density of nails snails in the Tongjiang River channel and the outer river bank and the emergence rate of snail frames both showed a significant increase, rising by 94.73% (0.18/0.19) and 68.08% (8.68/12.75) compared to 2020, and by 122.73% (0.81/0.66) and 102.78% (43.26/42.09), respectively. The differences in the increase in the occurrence rate of spiked frames in the Tongjiang River channel Chili River and Renmin River were not statistically significant (χ2=0.329, P>0.05; χ2=0.646, P>0.05). From 2022 to 2023, the density of nail snails and the occurrence rate of framed snails in the Tongjiang River channel showed a decreasing trend (F=4.72, P=0.04 and χ2=372.58, P<0.01). The area of nail snails, density of live snails, and occurrence rate of framed snails in the outer river bank showed a decreasing trend (F=13.96, P=0.02; F=23.43, P<0.01; χ2=1 029.69, P<0.01). During the five years, no nail snails were detected in the ancient canal and 11 tributaries. From 2019 to 2023, 180 times of 3 003 kg of floating objects were salvaged, with a total of 148 live snails detected. A total of 17 live snails were captured on attachments in the hardened berm area; a total of 11 live snails were captured by straw curtain snail baiting;112 boats were inspected, and no snails were found; there were 112 boats surveyed, and no snails were found; 97 cattle were observed, and 2 cattle were found to carry 1 live snail on their hooves; 321 sheep were observed, and no snails were found on their hooves; and no infectious snails were found in the monitoring area in 5 years. Conclusions　Nail snails continue to exist in the Tongjiang River channel, and the risk factors for schistosomiasis transmission have not been completely eliminated. It is still necessary to carry out accurate monitoring of the snail situation in the Tongjiang River and the river bank, so as to grasp the risk of transmission in time and take emergency measures.

Objective This study aims to conduct an evidence-based analysis of the research progress and management status of the competence of clinical department heads and nurse managers in China,providing reliable references for further devel-oping their management research and improving the human resource management in Chinese hospitals.Methods The VIP,CNKI,WANFANG Chinese databases,online resources,and relevant official websites were searched to retrieve literature related to the competence of clinical department directors and nurse managers in China.Descriptive analysis was conducted using biblio-metrics and evidence-based principles and methods.Results A total of 82 articles were included,mainly focusing on the con-ceptual theories of clinical department directors and nurse managers,the construction of competence models,and application re-search.The research on the competence of clinical department directors and nurse managers in China started relatively late and showed a trend of initial growth followed by decline.The distribution of journals was relatively scattered,and the literature mainly came from higher education institutions and medical institutions.The research development has stagnated at the stage of empirical research and has not progressed to the stage of evaluative research.Conclusion The research on the competence of clinical de-partment directors and nurse managers in China is still in the stage of application and practice,lacking systematic research.It is mainly led by higher education institutions and medical institutions,and the attention from the national government in terms of competence of clinical department directors and nurse managers in hospitals needs to be strengthened.

Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.