1.The effect of body mass index and inferior pulmonary ligament division on the residual lung expansion after right upper lobectomy: A retrospective cohort study in a single center
Guang MU ; Wenhao ZHANG ; Hongchang WANG ; Yan GU ; Chenghao FU ; Wentao XUE ; Shiyuan XIE ; Tong WANG ; Ke WEI ; Yang XIA ; Liang CHEN ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):261-266
Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2<BMI≤23 kg/m2), a group B (23 kg/m2<BMI≤29 kg/m2) and a group C (BMI>29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.
2.Rhodiolae Crenulatae Radix et Rhizoma protects brain microvascular endothelial cells from ischemia and hypoxia injury by regulating PI3K/AKT/GSK3β pathway.
Li TANG ; Qiu-Yue YANG ; Hong-Fa CHENG ; Ya-Hui XIE ; Qiu-Xia ZHANG
China Journal of Chinese Materia Medica 2025;50(11):3127-3136
This study elucidates the mechanism of Rhodiolae Crenulatae Radix et Rhizoma(RCRR) in protecting brain microvascular endothelial cells from oxygen-glucose deprivation(OGD) injury and reveals the modern pharmacological mechanism of RCRR's traditional use in nourishing Qi and promoting blood circulation to protect endothelial cells. The scratch assay was employed to assess the migratory capacity of endothelial cells. Immunofluorescence and Western blot techniques were employed to assess the protein expression of tight junction proteins zonula occludens-1(ZO-1), occludin, claudin-5, and proteins of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase-3beta(GSK3β) pathway. The results demonstrated that 63 bioactive components and 125 potential core targets of RCRR were identified from the ETCM, TCMBank, and SwissTargetPrediction databases, as well as from the literature. A total of 1 708 brain microvascular endothelial cell-related targets were identified from the GeneCards and OMIM databases, and 52 targets were obtained by intersecting drug components with cell targets. The protein-protein interaction(PPI) network analysis revealed that AKT1, epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), estrogen receptor 1(ESR1), proto-oncogene tyrosine-protein kinase(SRC), peroxisome proliferator-activated receptor gamma(PPARG), GSK3β, and matrix metalloproteinase 2(MMP2) were considered hub genes. The KEGG enrichment analysis identified the PI3K/AKT pathway as the primary signaling pathway. Cell experiments demonstrated that RCRR-containing serum could enhance the migratory capacity of brain microvascular endothelial cells and the expression of tight junction proteins following OGD injury, which may be associated with the downregulation of the PI3K/AKT/GSK3β pathway. This study elucidates the pharmacological mechanism of RCRR in protecting brain microvascular endothelial cells through network pharmacology, characterized by multiple components and targets. These findings were validated through in vitro experiments and provide important ideas and references for further research into the molecular mechanisms of RCRR in protecting brain microvascular endothelial cells.
Endothelial Cells/cytology*
;
Glycogen Synthase Kinase 3 beta/genetics*
;
Proto-Oncogene Proteins c-akt/genetics*
;
Drugs, Chinese Herbal/pharmacology*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Signal Transduction/drug effects*
;
Brain/metabolism*
;
Humans
;
Animals
;
Rhizome/chemistry*
;
Microvessels/metabolism*
;
Brain Ischemia/drug therapy*
3.Effects of Sishen Pills and its separated prescriptions on human intestinal flora based on in vitro fermentation model.
Jia-Yang XI ; Qi-Qi WANG ; Xue CHENG ; Hui XIA ; Lu CAO ; Yue-Hao XIE ; Tian-Xiang ZHU ; Ming-Zhu YIN
China Journal of Chinese Materia Medica 2025;50(11):3137-3146
Sishen Pills and its separated prescriptions are classic prescriptions of traditional Chinese medicine to treat intestinal diseases. In this study, a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry(HPLC-ESI-MS/MS) technology was used to identify the components of Sishen Pills, Ershen Pills, and Wuweizi Powder. The positive and negative ion sources of electrospray ionization were simultaneously collected by mass spectrometry. A total of 11 effective components were detected in Sishen Pills, with four effective components detected in Ershen Pills and eight effective components detected in Wuweizi Powder, respectively. To explore the effects of Sishen Pills and its separated prescriptions on the human intestinal flora, an in vitro anaerobic fermentation model was established, and the human intestinal flora was incubated with Sishen Pills, Ershen Pills, and Wuweizi Powder in vitro. The 16S rDNA sequencing technology was used to analyze the changes in the intestinal flora. The results showed that compared with the control group, Sishen Pills, and its separated prescriptions could decrease the intestinal flora abundance and increase the Shannon index after fermentation. The abundance of Bifidobacterium was significantly increased in the Sishen Pills and Ershen Pills groups. However, the abundance of Lactobacillus, Weissella, and Pediococcus was significantly increased in the Wuweizi Powder group. After fermentation for 12 h, the pH of the fermentation solution of three kinds of liquids with feces gradually decreased and was lower than that of the control group. The decreasing amplitude in the Wuweizi Powder group was the most obvious. The single-bacteria fermentation experiments further confirmed that Sishen Pills and Wuweizi Powder had inhibitory effects on Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis, and the antibacterial activity of Wuweizi Powder was stronger than that of Sishen Pills. Both Sishen Pills and Ershen Pills could promote the growth of Lactobacillus brevis, and Ershen Pills could promote the growth of Bifidobacterium adolescentis. This study provided a more sufficient theoretical basis for the clinical application of Sishen Pills and its separated prescriptions.
Humans
;
Gastrointestinal Microbiome/drug effects*
;
Drugs, Chinese Herbal/chemistry*
;
Fermentation/drug effects*
;
Bacteria/drug effects*
;
Chromatography, High Pressure Liquid
;
Tandem Mass Spectrometry
;
Intestines/microbiology*
4.Quality evaluation of Xinjiang Rehmannia glutinosa and Rehmannia glutinosa based on fingerprint and multi-component quantification combined with chemical pattern recognition.
Pan-Ying REN ; Wei ZHANG ; Xue LIU ; Juan ZHANG ; Cheng-Fu SU ; Hai-Yan GONG ; Chun-Jing YANG ; Jing-Wei LEI ; Su-Qing ZHI ; Cai-Xia XIE
China Journal of Chinese Materia Medica 2025;50(16):4630-4640
The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification*
;
Drugs, Chinese Herbal/chemistry*
;
Chromatography, High Pressure Liquid/methods*
;
Quality Control
5.Short-term outcomes of transcatheter pulmonary valve replacement with Venus-P valve in patients with moderate-to-severe pulmonary regurgitation and right ventricular systolic dysfunction.
Haiyue XIE ; Wenhao ZHU ; Zhiyuan XIA ; Gejun ZHANG
Journal of Zhejiang University. Medical sciences 2025;54(3):390-398
OBJECTIVES:
To evaluate the short-term outcomes of transcatheter pulmonary valve replacement (TPVR) using the Venus-P valve in patients with moderate-to-severe pulmonary regurgitation and right ventricular systolic dysfunction (RVSD) following surgical repair of complex congenital heart disease.
METHODS:
A retrospective analysis was conducted on patients undergoing Venus-P valve implantation (TPVR group, n=28) or surgical pulmonary valve replacement (SPVR group, n=19) at Fuwai Hospital between February 2014 and February 2024. All patients had moderate-to-severe pulmonary regurgitation with right ventricular ejection fraction less than 45% preoperatively. Postoperative pulmonary valve function and ventricular parameters were assessed at discharge and during a 6-month follow-up.
RESULTS:
All procedures were successfully completed with no early mortality. At 6 months, the TPVR group demonstrated significantly lower pulmonary valve transvalvular pressure gradients compared to the SPVR group (P<0.05). Both groups exhibited significant improvements from baseline in New York Heart Association (NYHA) functional class, biventricular ejection fractions, and right ventricular end-diastolic volume index (all P<0.05). The reduction in right ventricular end-diastolic diameter differed between the two groups (P<0.01). However, multivariable analysis revealed no association between this difference and surgical approach (β=4.4, P>0.05). In the TPVR group, QRS duration was significantly shortened postoperatively (P<0.01), with improvements in left ventricular end-diastolic volume index and cardiac index (both P<0.01), but these improvements did not differ significantly from the SPVR group (all P>0.05). During the follow-up, one patient in each group developed infective endocarditis within 1-month post-procedure; both were successfully treated with antibiotics. No other major complications were observed.
CONCLUSIONS
For patients with moderate-to-severe pulmonary regurgitation and RVSD, TPVR using the Venus-P valve effectively improves short-term pulmonary valve function and ventricular performance with a favorable safety profile, demonstrating potential as a minimally invasive alternative to SPVR .
Humans
;
Pulmonary Valve Insufficiency/surgery*
;
Retrospective Studies
;
Pulmonary Valve/surgery*
;
Heart Valve Prosthesis Implantation/methods*
;
Ventricular Dysfunction, Right/physiopathology*
;
Treatment Outcome
;
Female
;
Male
;
Child
;
Adult
;
Heart Valve Prosthesis
;
Adolescent
;
Cardiac Catheterization/methods*
;
Child, Preschool
6.Curative Efficacy Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with ASXL1 Mutation.
Ya-Jie SHI ; Xin-Sheng XIE ; Zhong-Xing JIANG ; Ding-Ming WAN ; Rong GUO ; Tao LI ; Xia ZHANG ; Xue LI ; Yu-Pei ZHANG ; Yue SU
Journal of Experimental Hematology 2025;33(3):720-725
OBJECTIVE:
To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation.
METHODS:
The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed.
RESULTS:
Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients.
CONCLUSION
Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans
;
Leukemia, Myeloid, Acute/therapy*
;
Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Middle Aged
;
Mutation
;
Adult
;
Repressor Proteins/genetics*
;
Adolescent
;
Retrospective Studies
;
Aged
;
Nucleophosmin
;
Young Adult
;
Transplantation, Homologous
;
Prognosis
;
Survival Rate
7.Robot-assisted percutaneous coronary intervention: a prospective, multicenter, randomized controlled, non-inferiority clinical trial.
Yi YU ; Zheng CHEN ; Zhi-Jian WANG ; Yue-Ping LI ; Li-Xia YANG ; Jing QI ; Jing XIE ; Tao HUANG ; Dong-Mei SHI ; Yu-Jie ZHOU
Journal of Geriatric Cardiology 2025;22(8):725-735
OBJECTIVE:
To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention (R-PCI) compared to traditional manual percutaneous coronary intervention (M-PCI).
METHODS:
This prospective, multicenter, randomized controlled, non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention. Participants were randomly assigned to either the R-PCI group or the M-PCI group. Primary endpoints were clinical and technical success rates. Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis < 30% with no 30-day major adverse cardiac events. Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system, without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter. Secondary endpoints included total procedure time, percutaneous coronary intervention procedure time, fluoroscopy time, contrast volume, operator radiation exposure, air kerma, and dose-area product.
RESULTS:
The trial enrolled 152 patients (R-PCI: 73 patients, M-PCI: 79 patients). Lesions were predominantly B2/C type (73.6%). Both groups achieved 100% clinical success rate. No major adverse cardiac events occurred during the 30-day follow-up. The R-PCI group had a technical success rate of 100%. The R-PCI group had longer total procedure and fluoroscopy times, but lower operator radiation exposure. The percutaneous coronary intervention procedure time, contrast volume, air kerma, and dose-area product were similar between the two groups.
CONCLUSIONS
For certain complex lesions, performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.
8.Mechanism of Banxia Houpo Decoction in Treating Gastroesophageal Reflux Disease: An Integrated Approach of Compound Analysis, Network Pharmacology and Empirical Verification.
Shun-Zhe SONG ; Jiang-Nan XIE ; Jing-Wen ZHANG ; Ai-Xia GONG
Chinese journal of integrative medicine 2025;31(10):889-898
OBJECTIVE:
To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification.
METHODS:
Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively.
RESULTS:
UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10-10 to 10-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10-7 to 3 × 10-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10-5 to 10-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged.
CONCLUSION
BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals
;
Gastroesophageal Reflux/physiopathology*
;
Drugs, Chinese Herbal/chemistry*
;
Rats, Sprague-Dawley
;
Network Pharmacology
;
Male
;
Serotonin/metabolism*
;
Rats
;
Disease Models, Animal
;
Serotonin Plasma Membrane Transport Proteins/metabolism*
;
Esophagus/drug effects*
9.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Arthritis, Rheumatoid/drug therapy*
;
Glucocorticoids/therapeutic use*
;
Medicine, Chinese Traditional
;
Retrospective Studies
10.Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite-stable colorectal cancer patients receiving immunotherapy.
Shijin YUAN ; Yan XIA ; Guangwei DAI ; Shun RAO ; Rongrong HU ; Yuzhen GAO ; Qing QIU ; Chenghao WU ; Sai QIAO ; Yinghua XU ; Xinyou XIE ; Haizhou LOU ; Xian WANG ; Jun ZHANG
Journal of Zhejiang University. Science. B 2025;26(4):371-392
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*

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