The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To observe the effects of tuina of"three methods and three acupoints"on skeletal muscle α-actin,myostatin(MSTN)and atrophy gene 1(Atrogin1)expression of sciatic nerve injury(SNI)rats;To explore the mechanism of tuina therapy on motor dysfunction.Methods Male SD rats were randomly divided into blank group,sham-operation group,model group and tuina group,with 9 rats in each group.SNI model was established by clamp method in rats of the model group and tuina group.The sciatic nerve was exposed without clamping in rats of the sham-operation group,the blank group was not intervened.7 days after the operation,the intelligent tuina manipulation simulator was used to simulate the point method,dial method and knead method,which were applied to the"Yinmen"(BL37),"Chengshan"(BL57)and"Yanglingquan"(GB34)of rats in the tuina group,once a day,for 20 times.The rats in the sham-operation group and the model group were only grasped and restrained.Rats in the blank group did not receive any intervention.The hind limb muscle strength were evaluated by inclined plate test before modeling,after 10 interventions and 20 interventions.After the intervention,the rats were euthanized.The expressions of α-actin in gastrocnemius muscle tissue were detected by immunofluorescence staining,the expressions of MSTN,Atrogin1 mRNA and protein in gastrocnemius muscle tissue were detected by RT-PCR and Western blot.Results Compared with the blank group and sham-operation group,the model group showed a decrease in hind limb muscle strength(P<0.01),a significant decrease in α-actin expression in gastrocnemius muscle tissue(P<0.01),and a significant increase in MSTN,Atrogen1 mRNA and protein expression(P<0.05,P<0.01).Compared with the model group,the hind limb muscle strength in tuina group significantly increased(P<0.01),the expressions of α-actin significantly increased(P<0.01),and the expressions of MSTN,Atrogin1 mRNA and protein significantly decreased(P<0.05,P<0.01).Conclusion"Three methods and three acupoints"tuina can improve hind limb muscle strength and restore motor function of SNI rats,which is related to the down-regulation of MSTN and Atrogin1 as well as increasing the expression of α-actin in gastrocnemius muscles.

Objective To explore the mechanism of abnormal metastable dynamics in Alzheimer disease(AD)using brain network dynamic model based on MRI.Methods Data of MR T1WI diffusion tensor imaging(DTI)and resting-state functional MRI(rs-fMRI)of 25 AD patients(AD group)38 mild cognitive impairment(MCI)patients(MCI group)and 37 healthy controls(HC group)in AD Neuroimaging Initiative(ADNI)database were collected.Based on abnormal brain structural connectivity and cortical atrophy characteristics of AD group the structural virtual injury brain network model was constructed and the mechanism of abnormal metastable dynamics in AD was explored.Results The abnormal functional connectivity of white matter in AD group was concentrated in visual network(VIS)default mode network(DMN)frontoparietal network(FPN)and limbic network(LIM).The overall metastable state of AD group in sensorimotor network(SMN)dorsal attention network(DAN)&ventral attention network(VAN)(i.e.attention network[AN])and DMN specific perturbation models were all significantly lower than that in HC group and MCI group respectively(all P＜0.001).In AD group local circuits abnormality could be seen in posterior right superior temporal gyrus precentral gyrus caudal anterior cingulate gyrus and isthmus of the cingulate gyrus leading to decrease in global metastability.The structural connection damage of DMN and AN as well as cortical atrophy of FPN had significant impact on metastable dynamics in AD patients.Conclusion Multimodal MRI brain network dynamic model revealed the core factors of mechanism of metastable dynamic decline in AD included DMN AN and FPN abnormalities.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Rheumatoid arthritis(RA)is a chronic autoimmune disease with a high risk of disability.Macrophages,as important immune cells,participate in the regulation of inflammatory response and bone homeostasis in RA by polarization to different phenotypes.This article reviewed the etiology and pathogenesis of RA in TCM.It was found that imbalance in macrophage polarization is a key factor contributing to inflammation and imbalance in bone homeostasis in RA.During the development of RA,M1 and M2 macrophages have different characteristics of yin and yang attributes and play different roles,which are similar to the connotation of mutual opposition,mutual restriction and mutual transformation of yin and yang theory of TCM.Based on yin-yang theory of TCM,it is proposed to regulate the balance of yin and yang and restore the homeostasis of macrophage to delay the progression of RA,hoping to provide ideas for clinical treatment of RA.

Objective To investigate the relationship between vertical laminar fracture(VLF)in thoracolumbar burst fractures and both neurological injury and dural tear.Methods A retrospective analysis was conducted on the clinical data and multi spiral computed tomography(MSCT)coronal images of 255 patients of thoracolumbar burst fractures.The patients were divided into three groups based on the presence of VLF[Ⅰ group(complete VLF group),Ⅱ group(partial VLF group),and Ⅲ group(normal lamina group)].Statistical analysis was performed using analysis of variance and Fisher's exact test to compare radiological parameters,inci-dence of dural tear,and neurological injury among the groups.Results The Ⅰ group showed significant differences in spinal canal sagittal diameter,pedicle distance,and spinal canal area compared with the other two groups(P<0.05).However,there was no sig-nificant difference in vertebral body compression rate between the Ⅰ group and the Ⅱ group(P>0.05).The Ⅰ group had the high-est incidence of severe neurological injury[American Spinal Injury Association(ASIA)impairment scale grades A and B]and dural tear(P<0.05).Conclusion The severity of VLF is closely related to dural tear and neurological injury.MSCT coronal images can clearly display the extent of VLF,providing an important basis for clinical evaluation and treatment plan.

[Objective]From the perspective of the analogy and metaphorical thinking,to explore YE Tianshi's characteristics in syndrome differentiation,treatment and medication in his work Case Records as A Guide to Clinical Practice.[Methods]The connotations of analogical and metaphorical thinking are discussed based on Yi·Xici(The Book of Changes)and Huangdi Neijing(The Yellow Emperor's Inner Canon).By studying Case Records as A Guide to Clinical Practice,the study analyzes disease mechanisms by referring to Five Movements and Six Qi,establishes therapeutic principles and methods by referring to organs and body functions,and guides medication by considering the"form"and"properties"of herbs.The influence of constitution and seasons on diagnosis and treatment is also considered.By employing research methods such as literature review and case analysis,particular attention is given to how YE Tianshi utilized analogy and metaphorical thinking to guide medication and treatment during the diagnostic process.[Results]The philosophical connotation of the concept of the analogy and metaphorical thinking mainly refers to the relationship of imitation among things.In traditional Chinese medicine,it can be divided into three categories:classification based on imitation,analogy based on imitation and interpretation of the Tao based on imitation.YE Tianshi applied analogy and metaphorical thinking clinically by referring Qi in analyzing disease mechanisms,referring to organs and body functions when establishing treatment principles,and using the"form"and"properties"of herbs to guide medication.He also emphasized constitution-based syndrome differentiation and seasonal treatments,highlighting the influence of the"harmony between heaven and humans"on human health.[Conclusion]In-depth study of YE Tianshi's application of analogy and metaphorical thinking in syndrome differentiation,treatment and medication can help better understand and apply analogy and metaphorical thinking,guiding modern traditional Chinese medicine clinical practice.

[Objective]From the perspective of the analogy and metaphorical thinking,to explore YE Tianshi's characteristics in syndrome differentiation,treatment and medication in his work Case Records as A Guide to Clinical Practice.[Methods]The connotations of analogical and metaphorical thinking are discussed based on Yi·Xici(The Book of Changes)and Huangdi Neijing(The Yellow Emperor's Inner Canon).By studying Case Records as A Guide to Clinical Practice,the study analyzes disease mechanisms by referring to Five Movements and Six Qi,establishes therapeutic principles and methods by referring to organs and body functions,and guides medication by considering the"form"and"properties"of herbs.The influence of constitution and seasons on diagnosis and treatment is also considered.By employing research methods such as literature review and case analysis,particular attention is given to how YE Tianshi utilized analogy and metaphorical thinking to guide medication and treatment during the diagnostic process.[Results]The philosophical connotation of the concept of the analogy and metaphorical thinking mainly refers to the relationship of imitation among things.In traditional Chinese medicine,it can be divided into three categories:classification based on imitation,analogy based on imitation and interpretation of the Tao based on imitation.YE Tianshi applied analogy and metaphorical thinking clinically by referring Qi in analyzing disease mechanisms,referring to organs and body functions when establishing treatment principles,and using the"form"and"properties"of herbs to guide medication.He also emphasized constitution-based syndrome differentiation and seasonal treatments,highlighting the influence of the"harmony between heaven and humans"on human health.[Conclusion]In-depth study of YE Tianshi's application of analogy and metaphorical thinking in syndrome differentiation,treatment and medication can help better understand and apply analogy and metaphorical thinking,guiding modern traditional Chinese medicine clinical practice.

Rheumatoid arthritis(RA)is a chronic autoimmune disease with a high risk of disability.Macrophages,as important immune cells,participate in the regulation of inflammatory response and bone homeostasis in RA by polarization to different phenotypes.This article reviewed the etiology and pathogenesis of RA in TCM.It was found that imbalance in macrophage polarization is a key factor contributing to inflammation and imbalance in bone homeostasis in RA.During the development of RA,M1 and M2 macrophages have different characteristics of yin and yang attributes and play different roles,which are similar to the connotation of mutual opposition,mutual restriction and mutual transformation of yin and yang theory of TCM.Based on yin-yang theory of TCM,it is proposed to regulate the balance of yin and yang and restore the homeostasis of macrophage to delay the progression of RA,hoping to provide ideas for clinical treatment of RA.