ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020.Methods:Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ 2 test/Fisher exact probability method. Results:Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M ( Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ 2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion:HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

Tic disorder is a common neuropsychiatric disorder in children and one of the common serious chronic diseases that endanger children's health.According to YE Tianshi's theory of"yang transforms into internal wind",water fails to nourish wood(kidney yin deficiency can not nourish liver wood),spleen deficiency and liver hyperactivity,wood stagnation and intense fire cause internal wind,and leading to frenetic stirring of tendons.Insect drugs are considered to be"pathogenic wind"in terms of pathogenic factors,and the pain wanders unsteadily.They have the effects of tonifying the kidney and supplementing essence,calming the liver and suppressing wind,resolving phlegm and relieving spasm,dispelling wind and purging heat,dredging collaterals and removing blood stasis,which exert certain effects in treating children with tic disorder.Modern pharmacological studies have shown that insect drugs can treat children with tic disorders from multiple perspectives such as anti-convulsion,regulation of neurotransmitters,inhibition of neuroinflammation,and regulation of immunity.Based on the theory of"yang transforms into internal wind",this paper analyzes the application of insect drugs in the treatment of children with tic disorder,which can provide theoretical reference for the prevention and treatment of tic disorder by traditional Chinese medicine.

Malignant tumors represent a significant health challenge, critically impacting human well-being. Malignant tumors have become one of the leading causes of death worldwide. According to statistics from the World Health Organization, nearly one-sixth of global deaths in 2020 were caused by malignant tumors. The burden of malignant tumors in our country is also increasing. In recent years, with population aging and changes in lifestyle, the incidence and mortality rates of malignant tumors in China have been steadily rising, malignant tumors have gradually become one of the main causes of death in China. Developing effective diagnostic and treatment methods is of great significance in reducing the burden of malignant tumors in our country. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not recapitulate the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, regulating tumor initiation and development are expected to open potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.

Malignant tumors represent a significant health challenge, critically impacting human well-being. Malignant tumors have become one of the leading causes of death worldwide. According to statistics from the World Health Organization, nearly one-sixth of global deaths in 2020 were caused by malignant tumors. The burden of malignant tumors in our country is also increasing. In recent years, with population aging and changes in lifestyle, the incidence and mortality rates of malignant tumors in China have been steadily rising, malignant tumors have gradually become one of the main causes of death in China. Developing effective diagnostic and treatment methods is of great significance in reducing the burden of malignant tumors in our country. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not recapitulate the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, regulating tumor initiation and development are expected to open potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.

Objective To investigate the mechanism of C-C motif chemokine ligand 5(CCL5)modulation by extracellular matrix stiffness in non-small cell lung cancer(NSCLC)and to determine the effect of CCL5 on the immunotherapy response of NSCLC.Methods The correlation between extracellular matrix stiffness and CCL5 expression in NSCLC was analyzed with the TCGA database.Polyacrylamide hydrogels with different stiffness were designed according to the extracellular matrix stiffness of NSCLC,and H1299 cells responding to the mechanical loading of hydrogel matrix stiffness were subjected to transcriptome sequencing.High matrix stiffness was verified to promote the expression of CCL5 by using sequence.Results High extracellular matrix stiffness upregulated CCL5 expression,and interferon-γ mediated signaling pathway might be involved in the process.NSCLC patients with high CCL5 expression had a greater abundance of cytotoxic T-cells in tumor tissue and reacted favorably to anti-programmed cell death protein 1 treatment.Conclusion Increased extracellular matrix stiffness promotes CCL5 synthesis,and CCL5 enhances immunotherapy responsiveness in NSCLC by increasing cytotoxic T cell infiltration in tumor tissue.

Malignant tumors represent a significant health challenge, critically impacting human well-being. Malignant tumors have become one of the leading causes of death worldwide. According to statistics from the World Health Organization, nearly one-sixth of global deaths in 2020 were caused by malignant tumors. The burden of malignant tumors in our country is also increasing. In recent years, with population aging and changes in lifestyle, the incidence and mortality rates of malignant tumors in China have been steadily rising, malignant tumors have gradually become one of the main causes of death in China. Developing effective diagnostic and treatment methods is of great significance in reducing the burden of malignant tumors in our country. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not recapitulate the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, regulating tumor initiation and development are expected to open potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.

Malignant tumors represent a significant health challenge, critically impacting human well-being. Malignant tumors have become one of the leading causes of death worldwide. According to statistics from the World Health Organization, nearly one-sixth of global deaths in 2020 were caused by malignant tumors. The burden of malignant tumors in our country is also increasing. In recent years, with population aging and changes in lifestyle, the incidence and mortality rates of malignant tumors in China have been steadily rising, malignant tumors have gradually become one of the main causes of death in China. Developing effective diagnostic and treatment methods is of great significance in reducing the burden of malignant tumors in our country. Historically, the focus has been on leveraging the biochemical cues of tumors for both diagnosis and treatment. While valuable, this strategy does not recapitulate the full complexity of tumor diagnosis and management. Recently, the integration of biomechanics and mechanobiology with oncology has highlighted the importance of mechanical cues, which have emerged as new hallmarks of tumors, regulating tumor initiation and development are expected to open potential novel routes for cancer diagnosis and therapeutic interventions. Despite the advances, a thorough literature review suggests a pronounced gap in our understanding of the mechanical properties of tumors. The clinical community has not yet completely recognized the diagnostic and therapeutic relevance of the mechanical cues of tumors. To bridge this knowledge gap, we propose and introduce the paradigm of "Tumor Mechanomedicine". We provide a comprehensive overview of the multi-scale mechanical characteristics of tumors, exploring their influence on tumor biology, from the aspects of tumor biomechanics, tumor mechanobiology, tumor mechanodiagnostics, and tumor mechanotherapeutics. By elucidating the diagnostic and therapeutic potential of these mechanical cues, we aim to furnish the oncology community with fresh insights, paving the way for innovative solutions to persistent clinical conundrums.