"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

BACKGROUND: PANoptosis has the features of pyroptosis, apoptosis, and necroptosis. Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure (ALF), but limited attention has been given to the crosstalk among them. In this study, we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment. METHODS: Three ALF-related datasets (GSE14668, GSE62029, and GSE74000) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Hub genes were identified through intersecting DEGs, genes obtained from weighted gene co-expression network analysis (WGCNA), and genes related to PANoptosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein‍‒‍protein interaction (PPI) analyses and gene set enrichment analysis (GSEA) were performed to determine functional roles. Verification was performed using an ALF mouse model. RESULTS: Our results showed that expression of seven hub genes (B-cell lymphoma-2-modifying factor (BMF), B-cell lymphoma-2-interacting protein 3-like (BNIP3L), Caspase-1 (CASP1), receptor-interacting protein kinase 3 (RIPK3), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA), uncoordinated-5 homolog B receptor (UNC5B), and Z-DNA-binding protein 1 (ZBP1)) was up-regulated in liver samples of patients. However, in the ALF mouse model, the expression of BNIP3L, RIPK3, phosphorylated RIPK3 (P-RIPK3), UACA, and cleaved caspase-1 was up-regulated, while the expression of CASP1 and UNC5B was down-regulated. The expression of ZBP1 and BMF increased only during the development of ALF, and there was no significant change in the end stage. Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers. Western blot results showed that pyroptosis, apoptosis, and necroptosis were always involved in lipopolysaccharide (LPS)/ d-galactosamine (d-gal)‍-induced ALF mice. The ALF cell model showed that bone marrow-derived macrophages (BMDMs) form PANoptosomes after LPS stimulation. CONCLUSIONS: Our results suggest that PANoptosis of macrophages promotes the development of ALF. The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.
Animals ; Liver Failure, Acute/genetics* ; Computational Biology ; Mice ; Pyroptosis/genetics* ; Humans ; Protein Interaction Maps ; Apoptosis/genetics* ; Necroptosis/genetics* ; Gene Regulatory Networks ; Gene Ontology ; Gene Expression Profiling ; Disease Models, Animal

Central memory T (Tcm) cells are a crucial subset in T cell development, playing an important role in long-term immune responses. Tcm cells exhibit strong proliferative capacity, long-term survival characteristics, and re-activation potential, enabling them to rapidly differentiate into effector T cells (Teff) upon antigen re-exposure, thus providing robust immune protection. The function of Tcm cells is regulated by various factors, including antigen exposure, cytokines, and metabolic conditions. A deeper understanding of their metabolic and epigenetic mechanisms under different pathological conditions will contribute to the development of more precise and effective immunotherapeutic strategies. This review elaborates on the origin and characteristics of Tcm cells, as well as their roles in antiviral responses, tumor immunity, and immunotherapy.
Humans ; Memory T Cells/cytology* ; Animals ; Immunologic Memory ; Neoplasms/therapy* ; Immunotherapy

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective The objective of this study was to analyze the 2021 global burden of disease database assessment of deaths and disability-adjusted life year(DALY)attributed to alcohol exposure induced malignant tumors in China,providing a scientif-ic basis for the prevention and control of alcohol exposure-related malignancies in China.Methods The 2021 global burden of dis-ease database were retrieved,analyzed the number of deaths and mortality,DALYs,and DALY rates for malignant tumors in China,and analyzed the mortality and DALY situations attributed to alcohol exposure for different gender and types of tumors.Results In 2021,the number of cancer-related deaths in China was 2.8178 million,accounting for 28.50%of the global total cancer deaths(2.8178 million vs.9.8884 million).The DALYs of malignant tumors in China were 2.8209 million person-year,accounting for 30.20%of the global DALY of malignant tumors(2.8209 million person-year vs.9.3407 million person-year).The mortality of malignant tumors attributed to alcohol exposure in males(12.80/100,000 vs.1.37/100,000)and DALY rate(354.08/100,000 vs.34.96/100,000)were higher than those in females.From the perspective of age distribution,the mortality of malignant tumors caused by alco-hol exposure increased with age,and the DALY rate reached its peak in the 70-year-old age group and then decreased again.The top three tumors with the highest disease burden caused by alcohol exposure were esophageal cancer,liver cancer,and colorectal cancer.Conclusion Alcohol exposure in China leads to a heavier burden of malignant tumor mortality and DALY,with higher in male malig-nant tumor mortality than that in females.Alcohol exposure mainly causes gastrointestinal tumors.The prevention and treatment of male gastrointestinal tumors should focus on alcohol exposure.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective The objective of this study was to analyze the 2021 global burden of disease database assessment of deaths and disability-adjusted life year(DALY)attributed to alcohol exposure induced malignant tumors in China,providing a scientif-ic basis for the prevention and control of alcohol exposure-related malignancies in China.Methods The 2021 global burden of dis-ease database were retrieved,analyzed the number of deaths and mortality,DALYs,and DALY rates for malignant tumors in China,and analyzed the mortality and DALY situations attributed to alcohol exposure for different gender and types of tumors.Results In 2021,the number of cancer-related deaths in China was 2.8178 million,accounting for 28.50%of the global total cancer deaths(2.8178 million vs.9.8884 million).The DALYs of malignant tumors in China were 2.8209 million person-year,accounting for 30.20%of the global DALY of malignant tumors(2.8209 million person-year vs.9.3407 million person-year).The mortality of malignant tumors attributed to alcohol exposure in males(12.80/100,000 vs.1.37/100,000)and DALY rate(354.08/100,000 vs.34.96/100,000)were higher than those in females.From the perspective of age distribution,the mortality of malignant tumors caused by alco-hol exposure increased with age,and the DALY rate reached its peak in the 70-year-old age group and then decreased again.The top three tumors with the highest disease burden caused by alcohol exposure were esophageal cancer,liver cancer,and colorectal cancer.Conclusion Alcohol exposure in China leads to a heavier burden of malignant tumor mortality and DALY,with higher in male malig-nant tumor mortality than that in females.Alcohol exposure mainly causes gastrointestinal tumors.The prevention and treatment of male gastrointestinal tumors should focus on alcohol exposure.

Objective:To observe the effect of taping on the kinematic characteristics of the ankle joint during forward and lateral jumps by male basketball players with chronic ankle instability (CAI).Methods:A Vicon 3D motion capture system and a Kistler 3D ergometer were used to collect data describing the landing data with or without taping from forward and lateral jumps of 29 male basketball players with CAI. The landing data included the dorsiflexion and plantarflexion angles, valgus and inversion angles and external and internal rotation angles. Dorsiflexion or plantarflexion angular velocity was also recorded along with valgus or inversion angular velocity and external or internal rotation angular velocity 200ms, 150ms, 100ms and 50ms before and after touchdown. The data obtained were modeled using three-dimensional motion analysis software, and then analyzed.Results:Taping reduced the ankle plantarflexion in landing from a forward jump by 3.27° 50ms before landing and by 2.70° at touchdown. The ankle inversion angle was reduced 2.13° 50ms before touchdown, while the angle of external rotation decreased by 2.59° 200ms before touchdown and 2.17° 150ms before. Moreover, the angle of external rotation 100ms after landing was reduced by a significant 1.59° compared with that without taping. In lateral jumps taping reduced the average ankle plantarflexion angle by 1.94° 50ms before landing and 3.23° at touchdown compared with no taping. Ankle inversion was reduced significantly by 2.86° 50ms before landing and by 2.87° at touchdown. External rotation was a significant 0.93° less 200ms before landing and 2.36° smaller 150ms before touchdown. In the forward jump landing, taping reduced the average angular velocity of ankle dorsiflexion on landing by a significant 58.5°/s and by 28.39°/s 100ms later. In the lateral jump landings the average ankle dorsiflexion velocity decreased by significant 20.5°/s with taping, but the valgus velocity increased by 49.7°/s compared with no taping. However, 50ms after touchdown the speed of external rotation with taping was 30.3°/s slower than without taping.Conclusions:Ankle taping can modify ankle rotation angles and angular velocities during landing from jumps. This is particularly helpful for basketball players with CAI.

Objective:To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI).Methods:Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3 software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0 software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 38 studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15 217 patients (9 130 in the trial group and 6 087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8 894) vs. 0.7% (49/6 584), RR=6.62 (95 %CI: 5.00-8.76), P<0.001; 2.5% (201/7 937) vs. 0.7% (41/5 831), RR=2.14 (95 %CI: 1.40-3.25), P<0.001; 1.5% (92/6 343) vs. 0.4% (21/4 870), RR=1.95 (95 %CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8 894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5 788) vs. 0.7% (32/4 428), RR=1.49 (95 %CI: 0.90-2.47), P=0.120; 1.7% (82/4 766) vs. 1.1% (40/3 628), RR=1.35 (95 %CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion:The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.

Objective:To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI).Methods:Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3 software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0 software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 38 studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15 217 patients (9 130 in the trial group and 6 087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8 894) vs. 0.7% (49/6 584), RR=6.62 (95 %CI: 5.00-8.76), P<0.001; 2.5% (201/7 937) vs. 0.7% (41/5 831), RR=2.14 (95 %CI: 1.40-3.25), P<0.001; 1.5% (92/6 343) vs. 0.4% (21/4 870), RR=1.95 (95 %CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8 894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5 788) vs. 0.7% (32/4 428), RR=1.49 (95 %CI: 0.90-2.47), P=0.120; 1.7% (82/4 766) vs. 1.1% (40/3 628), RR=1.35 (95 %CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion:The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.