High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.

Objective:To explore the impact and cost-effectiveness of community stroke screening intervention mode on stroke risk.Methods:A total of 3 561 community people over 40 years old who participated in screening intervention in 2017,2019 and 2021 were selected as research objects,and stroke risk was divided into low risk,medium risk and high risk.A Markov model was established to explore the impact of screening intervention mode on stroke risk in community population.The cost increment during the phase I trial was calculated,and the life year increment was adjusted according to the quality estimate of previous studies.The cost-effectiveness increment ratio was calculated,and the screening intervention mode was evaluated,and univariate sensitivity analysis was performed.Results:Within a certain range,intervention screening could effectively shift the status of residents to the low-risk direction,and finally stabilize the distribution of low-risk,medium-risk and high-risk were 47.4％,31.0％and 21.6％.The incremental cost of interventional screening was 160 245 yuan,the incremental quality-adjusted life year was 151.129 yuan,and the incremental cost-effectiveness ratio(ICER)was 1 060.319 yuan/QALY,which was less than 1 times the per capita GDP.The intervention program was fully cost-effective.Conclusion:Screening intervention can promote the transformation of the commu-nity population to a low-risk state of stroke in the prevention stage,and this approach has good cost-effectiveness performance.It is recommended that the primary medical and health institutions that are not enough to fully implement the integrated process ser-vice of community prevention and treatment of stroke should first implement low-cost screening intervention.