1.Validating the pathogenic mechanism of chronic obstructive pulmonary disease induced by negative emotions via Mendelian randomization and traditional Chinese medicine theory of emotions
Zhiying WANG ; Yun LI ; Zhixian ZHONG ; Ling XU ; Yi ZHONG ; Jian CHEN
Digital Chinese Medicine 2025;8(2):196-205
Objective:
We employed Mendelian randomization (MR) to test the traditional Chinese medicine (TCM) theory of emotional pathogenesis concept and explore the causal relationship between negative emotions and chronic obstructive pulmonary disease (COPD).
Methods:
Data of negative emotions, bronchitis, emphysema, and C-reactive protein (CRP) levels were downloaded from genome-wide association study (GWAS) public database for a two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with negative emotions, bronchitis, and emphysema were selected as instrumental variables. Primary causal estimates were derived using inverse-variance weighting (IVW), supplemented by weighted median (WM), and simple mode (SM) methods. Sensitivity analyses included MR-Egger regression and MR-PRESSO to assess pleiotropy, Cochran’s Q test for heterogeneity, and multivariate MR to adjust for smoking. Mediation analysis evaluated the role of inflammatory markers. Reverse MR was tested for bidirectional causality. Weak instrument bias was mitigated via F-statistic thresholds (> 10). All analyses were conducted in RStudio.
Results:
MR analysis identified significant causal effects of several negative emotions on COPD. Genetically, the IVW analysis of seen doctors for nerves anxiety tension or depression [ORIVW = 1.006, 95% CI = (1.002, 1.010), P = 0.002], sensitivity/hurt feelings [ORIVW = 1.024, 95% CI = (1.004, 1.044), P = 0.017], and irritability [ORIVW = 1.019, 95% CI = (1.003, 1.035), P = 0.019 were robustly associated with increased risks of COPD. No heterogeneity was detected among the different instrumental variables (IVs) for depression (P = 0.655) and irritability (P = 0.163). MR-Egger regression intercepts for all emotional exposures were close to zero and statistically non-significant, indicating no evidence of directional pleiotropy. The horizontal pleiotropy results showed that except for worry (MR-PRESSO P = 0.006), other emotion exposures confirming no substantial pleiotropic bias. Multivariable MR demonstrated that anxiety remained independently associated with COPD after adjusting for smoking (P = 0.002), while associations with other negative emotions were attenuated post-adjustment. The mediation analysis revealed that CRP mediated 3.93% of the total effect of anxiety on COPD. However, reverse MR analysis found no evidence of reverse causality.
Conclusion
This study confirmed the causal effects of negative emotions on COPD through MR analysis and revealed that negative emotions may trigger CRP production, which plays an essential mediating role in this relationship. This study provides a reliable modern theoretical basis for emotion theory in TCM.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
5.SHI Zaixiang's Clinical Experience in Using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤) to Treat High Fever in Sepsis
Tingting ZHU ; Yingying LIU ; Hailan CUI ; Zhiying REN ; Mingjing SHAO ; Yan BIAN ; Liyan WANG ; Zhenjie CHEN ; Yuan LIU ;
Journal of Traditional Chinese Medicine 2025;66(16):1645-1648
This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤). He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever, chills, and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile, soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice, treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids, using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect, particularly in cases where multiple anti-infective treatments have failed.
6.Organ medicine: New concept of life sciences.
Zhitao CHEN ; Shuangjin YU ; Zhiying LIU ; Yefu LI ; Haidong TAN ; Yifang GAO ; Qiang ZHAO ; Xiaoshun HE
Chinese Medical Journal 2025;138(8):934-936
8.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
9.Trends and factors associated with overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023
Chinese Journal of School Health 2024;45(8):1176-1180
Objective:
To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies.
Methods:
In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys.
Results:
The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively,showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05).
Conclusions
The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.
10.Association of health risk behaviors with obesity and depressive symptoms in middle school students
SUN Zhiying, ZHANG Xianwei, YUAN Wen, DONG Yanhui, XU Ke, ZHAO Saisai, CHEN Lu, LIU Zhonghui
Chinese Journal of School Health 2024;45(10):1505-1510
Objective:
To investigate the tendency of obesity and depressive symptoms in middle school students in Tianjin, so as to provide a reference for exploring the clustering patterns of health risk behaviors and their effects on obesity and depressive symptoms.
Methods:
A stratified cluster sampling method was used to investigate the obesity, depressive symptoms and health risk behaviors of middle school students from 16 counties of Tianjin from 2019 to 2023. The latent classes analysis was used to classify health risk behaviors. The χ 2 test and Logistic regression were used to analyze the effects of different categories on obesity and depression symptoms.
Results:
The obesity detection rate of middle school students in Tianjin from 2019 to 2023 first increased ( 20.90% in 2019, 23.35% in 2020) and then decreased and gradually stabilized (2021-2023:22.20%-22.69%), and the detection rate of depressive symptoms showed a decreasing trend (from 21.65% to 14.92%). The detection rate of comorbidity of obesity and depressive symptoms first increased (4.62% in 2019, 4.66% in 2020) and then gradually decreased to 3.43% in 2023, and the rate was higher in boys than in girls and higher in urban areas than in suburban areas. Latent category analysis classified health risk behaviors into four categories: lack of exercise group, poor behaviors such as sleep group, poor diet group and healthy group. After adjusting for demographic characteristics,the results of Logistic regression analysis showed that the co-occurrence risk of obesity and depression symptoms among the top three groups of middle school students were 1.35( OR=1.35, 95%CI =1.15-1.58), 4.20( OR=4.20, 95%CI =3.50-5.04), and 1.84( OR=1.84, 95%CI =1.40-2.38)times, compared to the healthy group ( P <0.05).
Conclusions
From 2019 to 2023, the comorbidity rate of obesity and depression among middle school students in Tianjin increased first and then decreased gradually. Interventions should be made in the aspects of exercise, diet, sleep and other behaviors.


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