ObjectiveTo explore the molecular mechanism through which modified Guizhi Fulingwan （MGZFLW） promotes apoptosis and inhibits prostate cancer through the miR-34a-5p/δ-like protein 1 （DLL1）/Notch signaling pathway based on the traditional Chinese medicine theory of Yang transforming Qi while Yin constituting form. MethodsThe optimal intervention conditions of MGZFLW-containing serum and docetaxel （DXT） were screened by the cell counting kit-8 （CCK-8） method. Human prostate cancer cells （PC-3） were allocated into blank， MGZFLW （10%）， and DXT （30 nmol·L^-1） groups. The effects of MGZFLW-containing serum on the migration and proliferation of PC-3 cells were evaluated by cell scratch and colony formation assays， and the apoptosis of PC-3 cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay. The cells were transfected with miR-34a-5p mimics and miR-34a-5p inhibitor. The mRNA levels of miR-34a-5p， DLL1， Notch1 and its downstream effector factors Notch1 intracellular domain （NICD1）， Hes family basic helix-loop-helix transcription factor 1 （Hes1）， and hairy/enhancer-of-split related with YRPW motif 1 （Hey1） were determined by Real-time PCR. The protein levels of DLL1， Notch1， NICD1， Hes1， and Hey1 were determined by a WES fully automatic protein system. The effect of miR-34a-5p on the DLL1-mediated Notch pathway was evaluated based on the results. Further， after MGZFLW-containing serum intervention， the expression of DLL1 and Notch1 was detected by the immunofluorescence （IF） assay， and the mRNA and protein levels of miR-34a-5p/DLL1/Notch pathway-related molecules were quantified by Real-time PCR and the WES fully automatic protein system， respectively， to explore the regulatory effect of MGZFLW-containing serum on the miR-34a-5p/DLL1/Notch pathway. ResultsMGZFLW-containing serum inhibited the viability， migration， and proliferation and promote the apoptosis of PC-3 cells （P<0.01）. The overexpression of miR-34a-5p down-regulated the mRNA and protein levels of key molecules in the DLL1/Notch signaling pathway and promoted cell apoptosis （P<0.01）， while inhibition of miR-34a-5p had the opposite effects. MGZFLW-containing serum reversed the activation of the DLL1/Notch pathway and the inhibition of apoptosis caused by miR-34a-5p inhibition， up-regulated the expression of miR-34a-5p， and down-regulated the expression of related molecules in this pathway （P<0.01）. ConclusionMGZFLW can up-regulate the expression of miR-34a-5p to inhibit the DLL1/Notch signaling pathway and promote the apoptosis of prostate cancer cells， thereby inhibiting prostate cancer. This study provides experimental evidence for clarifying the molecular mechanism of the anti-prostate cancer effect of this formula.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective:To investigate the feasibility of the combination of free breathing with the high-threshold, short-delay technique in reducing radiation dose and the volumes of iodinated contrast agent in coronary computed tomography angiography (CCTA) for obese patients.Methods:The data of 73 obese patients with weights > 85 kg and body mass indices (BMIs) > 30 kg/m 2 who received CCTA in the Radiology Department of the Peking University Third Hospital from February 2023 to May 2024 were prospectively collected. These patients were divided into a control group (31 patients) and an experimental group (42 patients). Data were collected from the control group and experimental groups under breath-holding and free-breathing conditions, respectively. The bolus tracking thresholds, delay times, and ICA injection durations were set at 100 HU, 7 s, and 12 s for the control group and at 250 HU, 2 s, and 8 s for the experimental group, respectively. Other scanning and reconstruction parameters of both groups were consistent. The CT values and their standard deviations ( SD) of both groups were assessed and compared, with the CT values involving the lumens of the aorta (AO) root, left anterior descending (LAD), left circumflex artery (LCX), and right coronary artery (RCA). The signal-to-noise ratios (SNR) and contrast-to-noise ratio (CNR) were also calculated. The subjective assessment of image quality was performed for the 18 coronary artery segments using a 4-point scale. The effective radiation doses ( E) and the volumes of iodinated contrast agent of both groups were recorded and compared. The statistical differences in the aforementioned parameters between the groups were tested and analyzed using the analysis of variance (ANOVA), the Mann-Whitney U test, or the χ 2 test. With the results of the ICA as the gold standard, the diagnostic performance of the combination of free-breathing with the high-threshold, short-delay technique in CCTA for obese patients was assessed. Results:There was no statistically significant difference ( P > 0.05) in coronary artery images between both groups, specifically regarding the CT, SNR, and CNR values of the lumens of the AO roots, LAD, LCX, and RCA, as well as the SD values of the AO roots. Both groups received subjective scores of ≥ 3 for coronary artery images, meeting the diagnostic criteria, with no statistically significant differences ( P > 0.05). Compared with the results of the ICA, the analyses of the coronary artery segments of 23 patients from the experimental group, revealed that the accuracy, sensitivity, and specificity of CCTA in the diagnosis of > 50% stenosis were 89%, 86%, and 97%, respectively. Compared to that (45 ml) of the control group, the volume (30 ml) of iodinated contrast agent of the experimental group decreased by 33.3%, with no statistically significant difference in the effective radiation dose ( E) between both groups ( P > 0.05). Conclusions:The combination of free breathing with the high-threshold, short-delay technique can further reduce the volume of the ICA for obese patients while maintaining high CCTA image quality and diagnostic performance.

Aim To study the effect of evodiamine(EVO)regulating forkhead box protein Ml(FOXM1)on the proliferation and apoptosis of colorectal cancer-resistant cells HCT8/5-FU.Methods CCK-8 assay and EdU assay were used to detect the effect of EVO on cell proliferation ability.Clone formation assay was employed to detect the effect of EVO on the clone for-mation ability of cells.Flow cytometric counting was applied to detect apoptosis.Western blot was utilized to detect the expression of cellular Bcl-2,Bax,FOXM1,β-catenin,c-MYC,and CyclinD1;Molecular docking was used to explore the EVO-FOXM1 interac-tion.Nude mouse transplant tumor model was estab-lished to validate the effect of EVO on HCT8/5-FU cells in vivo.Results CCK-8 assay showed that EVO inhibited the proliferation of HCT8/5-FU cells in a time-and concentration-dependent manner.EdU assay found that the newly proliferated cells in the EVO-trea-ted group were significantly reduced.The results of the clone formation assay showed that EVO inhibited the clone-forming ability of HCT8/5-FU cells.Flow cyto-metric counting found that apoptosis rate of the cells in the EVO group significantly increased.Western blot showed that FOXM1 and β-catenin were significantly highly expressed in HCT8/5-FU cells,and EVO down-regulated the expression of FOXM1,β-cateniin,c-MYC,CyclinD1,and Bcl-2,and up-regulated the ex-pression of Bax.Molecular docking revealed strong in-teractions between EVO and FOXM1.The in vivo ex-perimental results demonstrated that EVO exerted a substantial inhibitory effect on the growth of subcutane-ously implanted HCT8/5-FU xenograft tumors and regulated the expression of related proteins.HE stai-ning revealed significant nuclear consolidation and fragmentation of tumor cells in the EVO group.Con-clusions The findings suggest that EVO could sup-press the activation of the Wnt signaling pathway through a mechanism involving the downregulation of FOXM1 protein expression,thus inhibiting the prolifer-ation of HCT8/5-FU cells and induce their apoptosis.

Objective:To investigate the feasibility of the combination of free breathing with the high-threshold, short-delay technique in reducing radiation dose and the volumes of iodinated contrast agent in coronary computed tomography angiography (CCTA) for obese patients.Methods:The data of 73 obese patients with weights > 85 kg and body mass indices (BMIs) > 30 kg/m 2 who received CCTA in the Radiology Department of the Peking University Third Hospital from February 2023 to May 2024 were prospectively collected. These patients were divided into a control group (31 patients) and an experimental group (42 patients). Data were collected from the control group and experimental groups under breath-holding and free-breathing conditions, respectively. The bolus tracking thresholds, delay times, and ICA injection durations were set at 100 HU, 7 s, and 12 s for the control group and at 250 HU, 2 s, and 8 s for the experimental group, respectively. Other scanning and reconstruction parameters of both groups were consistent. The CT values and their standard deviations ( SD) of both groups were assessed and compared, with the CT values involving the lumens of the aorta (AO) root, left anterior descending (LAD), left circumflex artery (LCX), and right coronary artery (RCA). The signal-to-noise ratios (SNR) and contrast-to-noise ratio (CNR) were also calculated. The subjective assessment of image quality was performed for the 18 coronary artery segments using a 4-point scale. The effective radiation doses ( E) and the volumes of iodinated contrast agent of both groups were recorded and compared. The statistical differences in the aforementioned parameters between the groups were tested and analyzed using the analysis of variance (ANOVA), the Mann-Whitney U test, or the χ 2 test. With the results of the ICA as the gold standard, the diagnostic performance of the combination of free-breathing with the high-threshold, short-delay technique in CCTA for obese patients was assessed. Results:There was no statistically significant difference ( P > 0.05) in coronary artery images between both groups, specifically regarding the CT, SNR, and CNR values of the lumens of the AO roots, LAD, LCX, and RCA, as well as the SD values of the AO roots. Both groups received subjective scores of ≥ 3 for coronary artery images, meeting the diagnostic criteria, with no statistically significant differences ( P > 0.05). Compared with the results of the ICA, the analyses of the coronary artery segments of 23 patients from the experimental group, revealed that the accuracy, sensitivity, and specificity of CCTA in the diagnosis of > 50% stenosis were 89%, 86%, and 97%, respectively. Compared to that (45 ml) of the control group, the volume (30 ml) of iodinated contrast agent of the experimental group decreased by 33.3%, with no statistically significant difference in the effective radiation dose ( E) between both groups ( P > 0.05). Conclusions:The combination of free breathing with the high-threshold, short-delay technique can further reduce the volume of the ICA for obese patients while maintaining high CCTA image quality and diagnostic performance.

Aim To study the effect of evodiamine(EVO)regulating forkhead box protein Ml(FOXM1)on the proliferation and apoptosis of colorectal cancer-resistant cells HCT8/5-FU.Methods CCK-8 assay and EdU assay were used to detect the effect of EVO on cell proliferation ability.Clone formation assay was employed to detect the effect of EVO on the clone for-mation ability of cells.Flow cytometric counting was applied to detect apoptosis.Western blot was utilized to detect the expression of cellular Bcl-2,Bax,FOXM1,β-catenin,c-MYC,and CyclinD1;Molecular docking was used to explore the EVO-FOXM1 interac-tion.Nude mouse transplant tumor model was estab-lished to validate the effect of EVO on HCT8/5-FU cells in vivo.Results CCK-8 assay showed that EVO inhibited the proliferation of HCT8/5-FU cells in a time-and concentration-dependent manner.EdU assay found that the newly proliferated cells in the EVO-trea-ted group were significantly reduced.The results of the clone formation assay showed that EVO inhibited the clone-forming ability of HCT8/5-FU cells.Flow cyto-metric counting found that apoptosis rate of the cells in the EVO group significantly increased.Western blot showed that FOXM1 and β-catenin were significantly highly expressed in HCT8/5-FU cells,and EVO down-regulated the expression of FOXM1,β-cateniin,c-MYC,CyclinD1,and Bcl-2,and up-regulated the ex-pression of Bax.Molecular docking revealed strong in-teractions between EVO and FOXM1.The in vivo ex-perimental results demonstrated that EVO exerted a substantial inhibitory effect on the growth of subcutane-ously implanted HCT8/5-FU xenograft tumors and regulated the expression of related proteins.HE stai-ning revealed significant nuclear consolidation and fragmentation of tumor cells in the EVO group.Con-clusions The findings suggest that EVO could sup-press the activation of the Wnt signaling pathway through a mechanism involving the downregulation of FOXM1 protein expression,thus inhibiting the prolifer-ation of HCT8/5-FU cells and induce their apoptosis.

ObjectiveTo discriminate the age of Arisaema Cum Bile， the combination of headspace solid-phase microextraction （HS-SPME） with gas chromatography-mass spectrometry （GC-MS） was applied to explore the differences of volatile components of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented Arisaema Cum Bile. MethodSamples with different fermentation durations were collected and HS-SPME-GC-MS technology was employed to detect the volatile components of each sample. The relative contents of detected volatile components were processed and analyzed by chemometrics methods such as principal component analysis （PCA）， hierarchical cluster analysis （HCA）， and partial least squares discriminant analysis （PLS-DA）. ResultThe results showed that 145 volatile components were identified. Among these volatile components， the relative contents of heterocyclic， alcohols， aldehydes and aromatics were high. PCA， HCA， and PLS-DA can effectively separate Arisaema Cum Bile with four different ages. Based on variable importance in projection （VIP） value > 1， 73 markers of differential volatile components were identified. The content of 2，6，11-trimethyldodecane and m-xylene in unfermented samples was the highest， and the content difference between them and those in fermented samples was significant （P<0.05）. 2，3-butanediol was detected only in 1-year samples， octane was detected only in 2-year samples， and ethyl heptanoate was detected only in 3-year samples. These components can be used as odor markers for Arisaema Cum Bile with different fermentation years. ConclusionThe identification method of volatile components of Arisaema Cum Bile was established by HS-SPME-GC-MS technology， which can realize the rapid identification of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented samples， and provide a scientific basis for the standardization of processing technology and quality standards of Arisaema Cum Bile.

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.

Objective:To evaluate the performance of key performance indicator (KPI) lean teaching management system in clinical medical laboratory.Methods:Combining lean teaching management in universities with KPI system of enterprises, an innovative KPI lean teaching management system was developed and applied in Clinical Medical Laboratory of Guangdong Provincial People′s Hospital (GDPH). A total of 106 teachers, who had worked from January 2021 to December 2022 in GDPH, joined this study. Teachers were divided into 8 professional groups. Firstly, we quantified the teaching workload by class hours, evaluated the teaching outcomes base on national, provincial, school, and college levels to assign different teaching points, and linked the teaching KPI scores to the evaluation, salary, and professional title of teachers. Then, we analyzed the overall teaching points and teaching points for each professional group (2021-2022). Finally, we asked teaching managers, teachers, and colleagues to evaluate the KPI lean teaching management system and compared the effects before and after the implementation of this system.Results:Compared with 2021, the teaching scores of 106 teachers increased significantly from 1.0 (0.2, 2.7) to 3.8 (2.3, 6.0) in 2022 ( Z=8.1, P<0.01). The teaching scores of clinical molecules, clinical coagulation, clinical immunology, clinical microbiology, Huifu laboratory, and clinical biochemistry group were significantly higher in 2022 than the scores they got in 2021 (all P<0.05). Compared with 2021, there were 3 new set up of educational reform projects, 2 submitted teaching articles, 3 new competition awards, 7 outstanding teachers, and 5 outstanding students in 2022. After application of KPI lean teaching management, the evaluation scores of teaching work by teaching managers, teachers, and colleagues are all significantly improved ( P<0.05). Conclusion:KPI lean teaching management system could effectively enhance teachers′ work initiative, improve teaching efficiency and outcome, and promote the teaching quality. Therefore, based on the performance of KPI lean teaching management system in our study, it is possible to realize its potential in terms of lean management in clinical medical laboratory.