1.Availability and use of child safety seats among children aged 0-3 years
CHEN Bo ; WANG Xihui ; QIU Fengqian ; YU Yan ; GAO Shuna ; HE Lihua ; LI Weiyi ; JI Yunfang ; CHEN Weihua
Journal of Preventive Medicine 2025;37(1):21-25
Objective:
To investigate the availability and use of child safety seats among children aged 0-3 years, so as to provide the basis for improving riding safety for children.
Methods:
Parents of children aged 0-3 years in Huangpu District, Shanghai Municipality, were recruited using the stratified multistage random sampling method from May to July 2024. Demographic information, family travel patterns, the use of child safety seat and related health beliefs were collected using questionnaire surveys. Factors affecting the use of child safety seats were identified using a multivariable logistic regression model.
Results:
Totally 514 valid questionnaires were recovered, with an effective rate of 96.98%. The respondents included 122 fathers (23.74%) and 392 mothers (76.26%), with a median age of 34.00 (interquartile range, 5.00) years. There were 446 families equipping with child safety seats, accounting for 86.77%; and 169 families using child safety seats, accounting for 32.88%. Multivariable logistic regression analysis showed that the parents who had children aged >1-2 years (OR=0.597, 95%CI: 0.366-0.973), travelled 2-4 times per month (OR=0.359, 95%CI: 0.213-0.607) or once per month or less (OR=0.384, 95%CI: 0.202-0.729), and scored high in perceived barrier (OR=0.634, 95%CI: 0.486-0.827) were less likely to use child safety seats; the parents who had children with local household registration (OR=2.506, 95%CI: 1.356-4.633), travelled 5-<10 km (OR=1.887, 95%CI: 1.148-3.101) or ≥10 km (OR=2.319, 95%CI: 1.355-3.967), always wore seat belts (OR=2.342, 95%CI: 1.212-4.524), scored high in perceived susceptibility (OR=1.392, 95%CI: 1.091-1.778) and self-efficacy (OR=1.413, 95%CI: 1.156-1.727) were more likely to use child safety seats.
Conclusions
Equipping family cars with child safety seats and using them can prevent and reduce traffic injuries among children aged 0-3 years. It is recommended to strengthen publicity to promote the use of child safety seats.
2.Burden of pulmonary arterial hypertension in Asia from 1990 to 2021: Findings from Global Burden of Disease Study 2021.
Shenshen HUANG ; Jiayong QIU ; Anyi WANG ; Yuejiao MA ; Peiwen WANG ; Dong DING ; Luhong QIU ; Shuangping LI ; Mengyi LIU ; Jiexin ZHANG ; Yimin MAO ; Yi YAN ; Xiqi XU ; Zhicheng JING
Chinese Medical Journal 2025;138(11):1324-1333
BACKGROUND:
Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021.
METHODS:
Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index.
RESULTS:
In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates.
CONCLUSIONS
Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans
;
Global Burden of Disease
;
Male
;
Female
;
Middle Aged
;
Adult
;
Asia/epidemiology*
;
Prevalence
;
Aged
;
Pulmonary Arterial Hypertension/mortality*
;
Adolescent
;
Young Adult
;
Child
;
Child, Preschool
;
Infant
;
Hypertension, Pulmonary/epidemiology*
3.Impact of early detection and management of emotional distress on length of stay in non-psychiatric inpatients: A retrospective hospital-based cohort study.
Wanjun GUO ; Huiyao WANG ; Wei DENG ; Zaiquan DONG ; Yang LIU ; Shanxia LUO ; Jianying YU ; Xia HUANG ; Yuezhu CHEN ; Jialu YE ; Jinping SONG ; Yan JIANG ; Dajiang LI ; Wen WANG ; Xin SUN ; Weihong KUANG ; Changjian QIU ; Nansheng CHENG ; Weimin LI ; Wei ZHANG ; Yansong LIU ; Zhen TANG ; Xiangdong DU ; Andrew J GREENSHAW ; Lan ZHANG ; Tao LI
Chinese Medical Journal 2025;138(22):2974-2983
BACKGROUND:
While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients.
METHODS:
This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively.
RESULTS:
The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge.
CONCLUSION
Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans
;
Retrospective Studies
;
Male
;
Length of Stay/statistics & numerical data*
;
Female
;
Middle Aged
;
Adult
;
Psychological Distress
;
Inpatients/psychology*
;
Aged
;
Anxiety/diagnosis*
;
Depression/diagnosis*
4.Antipyretic effects of ethanol extracts of Arisaematis Rhizoma fermented with bile from different sources.
Run ZOU ; Fa-Zhi SU ; En-Lin ZHU ; Chen-Xi BAI ; Yan-Ping SUN ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(7):1781-1791
This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals
;
Rats
;
Male
;
Fermentation
;
Rats, Sprague-Dawley
;
Rhizome/metabolism*
;
Drugs, Chinese Herbal/chemistry*
;
Bile/chemistry*
;
Antipyretics/chemistry*
;
Fever/metabolism*
;
Cattle
;
Swine
;
Tumor Necrosis Factor-alpha/metabolism*
;
Ethanol/chemistry*
;
Interleukin-6/blood*
;
Interleukin-1beta/blood*
5.Synthesis of active substance 3,4-dihydroxyacetophenone from traditional Chinese medicine using Escherichia coli whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol.
Xi-Wei YUAN ; Yan-Qiu TIAN ; Wen-Yu WANG ; Ya-Lun ZHANG ; De-Hong XU
China Journal of Chinese Materia Medica 2025;50(5):1187-1194
The main active compound, 3,4-dihydroxyacetophenone(3,4-DHAP), in the leaves of Ilex pubescens var. glaber, exhibits various pharmacological activities, including vasodilation and heart protection. Currently, natural extraction and chemical synthesis are the primary methods for obtaining 3,4-DHAP, but both approaches have inherent challenges. To address these problems, this study explored the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant Escherichia coli, cultivated in a green, cost-effective medium at room temperature and atmospheric pressure. Firstly, this study successfully constructed recombinant E. coli S1, which contained only the HpaBC gene, and recombinant E. coli S3, which contained both the Hped and HpaBC genes. The ability of S1 and S3 to synthesize 3,4-DHAP from their respective substrates was then evaluated through whole-cell bioconversion. Based on these results, the effects of four factors, i.e., substrate concentration, IPTG concentration, induction temperature, and transformation temperature, on the whole-cell bioconversion yield of S3 were investigated using an orthogonal experiment. The results showed that the factors influenced the yield in the following order: transformation temperature > induction temperature > IPTG concentration > substrate concentration. The optimal conditions were found to be a transformation temperature of 35 ℃, IPTG concentration of 0.1 mmol·L~(-1), induction temperature of 25 ℃, and substrate concentration of 10 mmol·L~(-1). Finally, the effect of transformation time on the yield of 3,4-DHAP was further examined under the optimal conditions. The results indicated that as the transformation time increased, the yield of 3,4-DHAP steadily increased. The highest yield of 260 mg·L~(-1) with a productivity of 17% was achieved after 72 hours of transformation. In conclusion, this study successfully achieved the whole-cell bioconversion of 1-(4-hydroxyphenol)-ethanol to 3,4-DHAP using recombinant E. coli for the first time, laying the groundwork for further optimization and development of the biosynthesis of 3,4-DHAP.
Escherichia coli/genetics*
;
Acetophenones/chemistry*
;
Ethanol/chemistry*
;
Drugs, Chinese Herbal/chemistry*
;
Biotransformation
6.Hypolipidemic effect and mechanism of Arisaema Cum Bile based on gut microbiota and metabolomics.
Peng ZHANG ; Fa-Zhi SU ; En-Lin ZHU ; Chen-Xi BAI ; Bao-Wu ZHANG ; Yan-Ping SUN ; Hai-Xue KUANG ; Qiu-Hong WANG
China Journal of Chinese Materia Medica 2025;50(6):1544-1557
Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Rats
;
Male
;
Metabolomics
;
Hyperlipidemias/microbiology*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats, Sprague-Dawley
;
Hypolipidemic Agents/pharmacology*
;
Liver/metabolism*
;
Humans
;
Alanine Transaminase/metabolism*
;
Triglycerides/metabolism*
;
Aspartate Aminotransferases/metabolism*
7.Early effectiveness of arthroscopic modified tri-anchor double-pulley suture-bridge technique in repairing medium-sized supraspinatus tendon tears.
Peiguan HUANG ; Xiaoxu WANG ; Bei WANG ; Guanghua TAN ; Liang HONG ; Fang WANG ; Zhi ZENG ; Saiyun LEI ; Mingjun QIU ; Huyong YAN ; Chunrong HE
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(6):708-714
OBJECTIVE:
To describe a novel arthroscopic technique of modified tri-anchor double-pulley suture-bridge in repairing medium-sized supraspinatus tendon tears and evaluate the early effectiveness.
METHODS:
Between June 2021 and January 2024, 26 patients with medium-sized supraspinatus tendon tears who underwent arthroscopic modified tri-anchor double-pulley suture-bridge repair and met the selective criteria were included. There were 11 males and 15 females with an average age of 61.4 years (range, 43-74 years). Five patients had a significant history of trauma, while the remaining 21 patients had no apparent cause. The time from symptom onset to hospitalization was 3-25 months (mean, 7.9 months). The effectiveness was evaluated during follow-up, including the scores of University of California at Los Angeles (UCLA), American Shoulder and Elbow Surgeons (ASES), visual analogue scale (VAS), the range of forward flexion, abduction, external rotation, and internal rotation, and patient's satisfaction. Either MRI or ultrasound examination were used to evaluate structural integrity of the tendon.
RESULTS:
The operation time was 65-110 minutes (mean, 81.8 minutes). All patients were followed up 12-43 months (mean, 23.0 months). At 3 and 12 months after operation, the shoulder range of flexion, abduction, external rotation, and internal rotation, and the scores of VAS, UCLA, and ASES significantly improved when compared with those before operation ( P<0.05). The improvement was further observed at 12 months compared to 3 months ( P<0.05). At last follow-up, 13 patients were very satisfied with the effectiveness, 11 patients were satisfied, 1 was relatively satisfied, and 1 was dissatisfied. During follow-up, 15 patients underwent imaging examination and imaging reexamination showed that the re-tear rate of tendon was 6.6%(1/15). The remaining 11 patients refused imaging examination. Complications included partial anchor withdrawal in 1 case, shoulder stiffness in 5 cases, and mild pain in shoulder joint in 2 cases in physical activity or heavy physical activity.
CONCLUSION
Arthroscopic modified tri-anchor double-pulley suture-bridge technique is a novel surgical technique that uses double-loaded suture anchors as medial- and lateral-row anchors. In repairing medium-sized supraspinatus tendon tears, 6 sets of double-pulley suture-bridges can be created from one medial-row anchor; knotless medial-row can reduce re-tear rate of the tendon; good early effectiveness is obtained.
Humans
;
Female
;
Male
;
Middle Aged
;
Arthroscopy/methods*
;
Adult
;
Rotator Cuff Injuries/surgery*
;
Aged
;
Suture Techniques
;
Treatment Outcome
;
Suture Anchors
;
Rotator Cuff/surgery*
;
Range of Motion, Articular
;
Tendon Injuries/surgery*
;
Patient Satisfaction
8.Effects of MTHFR and GGH gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate therapy in children with acute lymphoblastic leukemia.
Lin-Xiao TENG ; Qi AN ; Lei WANG ; Nan WANG ; Qing-Ling KONG ; Rui HAN ; Yuan WANG ; Lu LIU ; Yan WANG ; Shu-Mei XU ; Kun-Peng SHI ; Fang-Shan QIU ; Xi-Xi DU ; Jin-Rui SHI
Chinese Journal of Contemporary Pediatrics 2025;27(7):802-807
OBJECTIVES:
To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL).
METHODS:
Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed.
RESULTS:
In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05).
CONCLUSIONS
Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans
;
Methotrexate/toxicity*
;
Methylenetetrahydrofolate Reductase (NADPH2)/genetics*
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*
;
Male
;
Female
;
Child
;
Child, Preschool
;
gamma-Glutamyl Hydrolase/genetics*
;
Antimetabolites, Antineoplastic/adverse effects*
;
Infant
;
Polymorphism, Genetic
;
Adolescent
;
Genotype
;
Polymorphism, Single Nucleotide
9.Xuefu Zhuyu Decoction Improves Blood-Brain Barrier Integrity in Acute Traumatic Brain Injury Rats via Regulating Adenosine.
Yang WANG ; Qiu-Ju YAN ; En HU ; Yao WU ; Ruo-Qi DING ; Quan CHEN ; Meng-Han CHENG ; Xi-Ya YANG ; Tao TANG ; Teng LI
Chinese journal of integrative medicine 2025;31(7):624-634
OBJECTIVE:
To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments.
METHODS:
Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence.
RESULTS:
XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity.
CONCLUSIONS
XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Blood-Brain Barrier/metabolism*
;
Brain Injuries, Traumatic/metabolism*
;
Adenosine/metabolism*
;
Male
;
Rats, Sprague-Dawley
;
Rats
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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